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HL, I understand completely and maybe I shouldn't have said the important part of that Oncologie article was...as I have been taking a different angle on all this in that we all know Big Pharma is corrupt on many levels
We know PS Targeting works
We know PS Targeting is safe
We know the IP was stolen in a way, the ONLY consideration I give is someone wanted in the hands it sits now vs others that could completely shelf it or more harmful ties to stealing the IP 100% (which some had to have know due to Federal Investigations)
We know about the Big Pharma sandbox where some agreements are respected in however which way you want to call it...and is this what Oncologie is doing?
Why wouldn't the BP with the #1 killer such as NSCLC where Bavi was just proven to be REQUIRED to boost ones immune system to optimal levels where one can handle some toxicity of another drug..why wouldn't an immediate action be taken to file with FDA to allow Bavi as the primer?
Why is Oncologie going down a road with other high unmet needs?
Is it part of the sandbox or simply too much resistance to go after NSCLC? Has some BP said stay away from here and you go there for now ...
Many questions and now we go back to queerioning all this ...where a Chinese Billionaire with ties to Thousand Talents program with ties to IP espionage etc ...had somehow chosen Laura Benjamin to run Oncologie and all this would never happen if someone did not choose? Ronin Capital / John Springs Stafford to pick apart Peregrine and shift the IP over
No way was it all a coincidence ...just like the passing of PS Targeting inventor patent holder Dr Phil Thorpe that had just sabotage in CSM Clinical Supplies Management with Jeanette Bleecker and CEO Gerald Finken all in the mix ...
Remember the drug that was at stake was Opdivo that would have NEVER been approved by FDA if that sabotage did not happen
The FDA must be astronomically amazed that some Big Pharma not filing to have PS Targeting as an immune cell primer in order to maximize the OS benefit for Keytruda etc ...or the FDA is well aware of the sandbox
Nothing will be accomplished unless many more send in their complaints with the facts
Now back to wondering why Laura Benjamin wanted to disclose WHEN she met Jimmy Wei...it was AFTER she formed her own company and AFTER she discovered some "material" known as Bavituximab
Jimmy Wei sits on BOD and had other sandbox interests it seems ...but he just so happened to meet Dr Benjamin...and who set that up?
Time will tell
Horselover, the key is Laura mentioning when she met Jimmy Wei ...when and why she started her own company
Dr Benjamin was one of the "Dozens" of collaborations that were on going that Steve King discussed
Let me guess ...would Jimmy Wei like to bid openly for PS Targeting IP or TRY to pick it up for breadcrumbs?
Next, John Springs Stafford did not know of Jimmy Wei? Lol
Thousand Talents of China ties ...now the IP espionage becoming public info last few months...
Does not take much to out some other key puzzle pieces together
Build CDMO Avid and appease the shareholders ...the question is the current BOD may not believe anymore a quick sell off as we hit new highs will happen
The IP is astronomical and the way it was shifted ...without fiduciary duty is a big problem
Oh...but Laura Benjamin just happened to agree with Jimmy Wei
Min Tang (Dana Farber ties) still with Avid ? Hmmm
Wei Sun PhD
Professor | Beijing, Beijing China
Specialties : Biotechnology Speaks about : Biotechnology
Biography :
Dr. Wei Sun is Albert Soffa Chair Professor of Mechanical Engineering, Drexel University, Philadelphia, USA, and National "Thousand-Talents" Distinguished Professor and Director of Biomanufacturing Research Center, Department of Mechanical Engineering, Tsinghua University, Beijing, China. Dr. Sun's research has been on Biofabrication, Computer-Aided Tissue Engineering, CAD/CAM and Additive Manufacturing.
https://www.emedevents.com/speaker-profile/wei-sun
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Did Laura E Benjamin know Min Tang of Peregrine? I would certainly say so and ties to Wei Sun with DIRECT ties to "Thousand Talents" of China and IP Espionage in the disclosed PRs as of late ?
I think it is time to all reach out to SEC FBI DOJ and the naked short Trading likely part of manipulating stock prices as right now, we must ask why in hell was there no competitive bid placed out vs with the help of John Springs Stafford the IP got hijacked over to Oncologie and now Laura Benjamin must feel some of the heat
The IP is worth Billions
The key statement in that article when Laura Benjamin says "...When I was an entry level researcher, I got an idea about how to effectively target tumor microenvironment with drugs" ...CEO Laura said that when she discovered an interesting material called 'Bavituximab', she (THEN decided) decided to establish her own company. At this time she met Jimmy Wei of Pivotal Bioventure China.
....oh, how interesting this will get...PS Targeting always was astronomical so hold those shares as naked shorting a few hundred shares here and there try to loosen some up that fail to understand that breakeven is upon Avid CDMO and PS Targeting ready soon
Avid will rebound soon..
Oncologie’s Development Strategy of Anticancer Treatment Drug with 'Stroma Biomarker'
2019-08-05 13:26 ?? 2019-08-05 13:26
http://m.biospectator.com/view/news_view.php?varAtcId=8193
Moving along nicely but we have not heard of all the shenanigans in the background surrounding PS Targeting IP ...things will be coming as Kyla Driscoll involved in PS Targeting
June 14 2018
Todays guest blog comes from Kyla Driscoll, Ph.D., senior research advisor and group leader focused on Lillys immuno-oncology drug discovery and development and Emily Collins, Ph.D., senior director of imaging research and development working across the Lilly portfolio including Lillys pain portfolio. Kyla and Emily recently traveled to Washington, D.C. with their Lilly colleague Jirong Lu, Ph.D., to talk about their work with Members of Congress and Capitol Hill staff. Here is a recap of their trip, in their own words.
https://lillypad.lilly.com/entry.php?e=10976
Choe publicly backing PS Targeting (March 27, 2014) when state stated "This is where the trouble begins..." when PS flips to the outside of the cellular membrane. She seems to be raising the alarm "arms race" on these viruses below.
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"Scientifically, it's as good as it gets because you're married to the collaboÂrator that you trust the most," he said. "Sometimes it seeps into the marriage half of lifeâ??and sometimes work creeps too much into life. But on balance I would call it a good thing. It's no question that it helps the marriage, it strengthens it because you're with somebody who knows all aspects of you."
Having settled into a condo on the beach in Juno Beach, both are glad to be at Scripps Florida and in Florida.
They walk on the beach. Choe admits that Farzan does it more than she does and that she was a little worried about how hot it would be when they finally settled into the Sunshine State.
"I thought it would be too hot and too humid," she said, "but we adapted to it so fast and now we can't live anywhere else. It's so funny that I worried about the weather."
HIV Vaccine Demonstrates Durability Against Hard-to-Fight Strains
Publish Date:
Wednesday, July 31, 2019
An investigational vaccine successfully protected against hard-to-fight HIV strains, with long-term efficacy from a single inoculation, according to a study published in Science Translational Medicine.
The vaccine, developed by researchers at the Scripps Research Florida campus, was tested against SIVmac239, also called the â??death starâ? strain, which is known for being seemingly indestructible, according to the study. SIVmac239 is a type of simian immunodeficiency virus that replicates HIV in primates.
Different from most conventional vaccines, this vaccine uses a safe virus to fight the dangerous one, using muscle cells rather than immune cells to generate protective agents. The lab-made adeno-associated virus (AAV) carries a protective protein called eCD4-Ig, ****** which features 2 HIV co-receptors: CD4 and CCR5. ****** Once injected into the muscle, the vaccine causes muscle cells to produce this protective protein, which prevents HIV from being able to infect.
â??We have solved 2 problems that have plagued HIV vaccine studies to dateâ??namely, the absence of duration of response and the absence of breadth of response,â? lead author Michael Farzan, PhD, said in a press release. â??No other vaccine, antibody, or biologic protects against the 2 viruses for which we have demonstrated robust protection.â?
For the study, the researchers tested the ability of eCD4-Ig to prevent SIVmac239 infection in macaques, administering eCD4-Ig to primates with the AAV before repeated escalated doses of the infection. Overall, the findings showed that the vaccine offered complete protection from high-dose SIVmac239 challenges that infected all 8 of the research animals. However, the study showed that animals could eventually become infected when exposed to atypically large loads of HIV, and that the virus is also capable of developing resistance to eCD4-Ig.
Subsequent analysis showed viral loads in the treated group were lower and eCD4-Ig put selective pressure on SIV, according to the study.
â??The results of our paper are encouraging for the potential of AAV as a platform for prevention of disease generally, and in concert with eCD4 as an agent for stopping HIV infection,â? Dr Farzan concluded. â??We hope ultimately to prove that our approach is safe for both infected and at-risk persons at a cost that makes it useable everywhere.â?
References
Farzan M,
Gardner MR,
Fellinger CH, et al.
AAV-delivered eCD$-Ig protects rhesus macaques from high-dose SIVmac239 challenges. Science Translational Medicine. 2019. DOI: 10.1126/scitranslmed.aau5409
https://www.specialtypharmacytimes.com/news/hiv-vaccine-demonstrates-durability-against-hard-to-fight-strains
Fusion Stage of HIV-1 Entry Depends on Virus- Induced Cell Surface Exposure of Phosphatidylserine
Page 1 of 33
Highlights
-HIV-cell binding triggers phosphatidylserine (PS) exposure at the cell surface
-PS exposure depends on gp120-coreceptor interactions, Ca2+ signaling, and TMEM16F
-Suppression of PS exposure inhibits Env restructuring, viral fusion, and infection
-PS signaling, a hallmark of activation, facilitates HIV entry
Elena Zaitseva,1
Eugene Zaitsev,1
Kamran Melikov,1
Anush Arakelyan,2
Mariana Marin,3
Rafael Villasmil,4
Leonid B. Margolis,2
Gregory B. Melikyan,3 and
Leonid V. Chernomordik1,5,*
1Section on Membrane Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
2Section on Intercellular Interactions, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
3Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
4Flow Cytometry Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
5Lead Contact
*Correspondence: chernoml@mail.nih.gov
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https://www.cell.com/cell-host-microbe/pdfExtended/S1931-3128(17)30252-4
Avid Bioservices BOD had decided to structure their unique business plan as I would say mostly a CDMO that has the very unique advantage of having milestones / royalties etc etc all tied to PS Targeting IP with all the manufacturing rights which easily would dwarf all other normal CDMO business. Biomarkers were required.
Here is the issue, only the last few months has it become more evident via disclosures that there was a long, long Federal Investigation in regards to other Countries stealing IP away from the US. It is only now becoming more and more clear how important it is for the cure for cancer and HIV etc AND placing the IP in the proper hands that deserve it as Billions of Dollars $$$ are at stake.
Gordon Freeman being awarded co-patent owner is exactly what came out of the investigations and Gordon knows well of flipped PS and the long list of supporters include Hyeryun Choe.
The problem is not all of us are privy to inside FBI etc investigations but the US President is and is this why we are this close to a cure for cancer / viral / HIV ? I say hell yes.
Remember, Avid Bioservices receives all the contracts tied into PS Targeting from Oncologie Inc. The same Oncologie Inc company that was formed in 30 days in order to shift the IP assets into and would this have been done during all the Federal Investigations?
Time will tell but it is clear John Springs Stafford was chosen for a job and that was to pull the PS Targeting IP into the Oncologie Inc umbrella all backed by Pivotal Bioventures which in turn was backed by a single Chinese Billionaire.
More to come...
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Hyeryun Choe knows ... Gordon Freeman knows and we will all know soon how vital it is to target flipped PS
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Hyeryun Choe stated back in 2014
"The viruses take advantage of the process that normally occurs during programmed cell death. During programmed cell death (â??apoptosisâ?), a lipid usually found on the inner side of the cell membranes, specifically phosphatidylserine (PS), shifts to the surface, making itself readily available to any passing cellular stranger. This is where the trouble begins"
and does Gordon Freeman work with Hyeryun ? Hell yes
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TIM-family Proteins Promote Infection of Multiple Enveloped Viruses through Virion-associated Phosphatidylserine
Stephanie Jemielity,
Jinyize J. Wang,
Ying Kai Chan,
Asim A. Ahmed,
Wenhui Li,
Sheena Monahan,
Xia Bu,
Michael Farzan,
Gordon J. Freeman,
Dale T. Umetsu,
Rosemarie H. DeKruyff,
Hyeryun Choe
PLOS
Published: March 28, 2013
DOI: 10.1371/journal.ppat.1003232
https://investorshub.advfn.com/boards/replies.aspx?msg=115148209
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Phosphatidylserine flipping by the P4-ATPase ATP8A2 is electrogenic
Francesco Tadini-Buoninsegni, Stine A. Mikkelsen, Louise S. Mogensen, Robert S. Molday, and Jens Peter Andersen
PNAS first published August 1, 2019
Significance
Phospholipid flippases constitute the largest subfamily of P-type ATPases and have in eukaryotic organisms evolved as a central transport system for selective translocation of phospholipids across biological membranes to generate membrane lipid asymmetry, a property essential for numerous cellular processes. The importance of flippases is highlighted by severe neurological disorders and liver diseases caused by flippase dysfunction in humans. The electrogenicity of phospholipid transport by flippases has not previously been explored. We demonstrated that phosphatidylserine translocation by the flippase ATP8A2 generates electrical current, resulting from specific steps in the flippase reaction cycle moving the charged lipid head group between the membrane bilayer leaflets, and that no charged substrate is being countertransported. These findings unravel key features of phospholipid flippases.
Abstract
Phospholipid flippases (P4-ATPases) utilize ATP to translocate specific phospholipids from the exoplasmic leaflet to the cytoplasmic leaflet of biological membranes, thus generating and maintaining transmembrane lipid asymmetry essential for a variety of cellular processes. P4-ATPases belong to the P-type ATPase protein family, which also encompasses the ion transporting P2-ATPases: Ca2+-ATPase, Na+,K+-ATPase, and H+,K+-ATPase. In comparison with the P2-ATPases, understanding of P4-ATPases is still very limited. The electrogenicity of P4-ATPases has not been explored, and it is not known whether lipid transfer between membrane bilayer leaflets can lead to displacement of charge across the membrane. A related question is whether P4-ATPases countertransport ions or other substrates in the opposite direction, similar to the P2-ATPases. Using an electrophysiological method based on solid supported membranes, we observed the generation of a transient electrical current by the mammalian P4-ATPase ATP8A2 in the presence of ATP and the negatively charged lipid substrate phosphatidylserine, whereas only a diminutive current was generated with the lipid substrate phosphatidylethanolamine, which carries no or little charge under the conditions of the measurement. The current transient seen with phosphatidylserine was abolished by the mutation E198Q, which blocks dephosphorylation. Likewise, mutation I364M, which causes the neurological disorder cerebellar ataxia, mental retardation, and disequilibrium (CAMRQ) syndrome, strongly interfered with the electrogenic lipid translocation. It is concluded that the electrogenicity is associated with a step in the ATPase reaction cycle directly involved in translocation of the lipid. These measurements also showed that no charged substrate is being countertransported, thereby distinguishing the P4-ATPase from P2-ATPases.
https://www.pnas.org/content/early/2019/07/31/1910211116
Published July 31, 2019 and Dr Rolf Brekken with several researchers that worked with the late Dr Phil Thorpe etc etc and why? Not a mere mention of Oncologie Inc on this PS Targeting research so why no mention?
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When I looked at the volume that it took to take it down last couple of hours just had to laugh. Like trying to scare a few people on the fence.
More interesting is the sell from Bandera about the same buy from our latest hedge fund Roubaix Capital
Maybe Madeline Elaine Hedges (Chief Compliance Officer) with Bandera now for a couple months may know ( ex Dinsmore & Shohl LLP who has exosome patent clients etc )
Exosomes are alive and well in demand if one has the patents
We wait till August 15th timeframe to see the increase but one should remember the % we see in August does not include the buys from July 1st +
Biomarkers Biomarkers Biomarkers will feed CDMO Avid and prepare for a future forward split as the float gets smaller
Could we get to $7?
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In addition to the validation of PS as an effective pharmacodelivery target for SMDC, our work also provided the foundation that, if applicable, a variety of therapeutic agents could be conjugated in the same manner to treat other PS-associated diseases.
..Published July 31, 2019 and Dr Rolf Brekken with several researchers that worked with the late Dr Phil Thorpe etc etc and why? Not a mere mention of Oncologie Inc on this PS Targeting research so why no mention?
Is Oncologie Inc all truthful?
Is John Springs Stafford all truthful?
Is PS Targeting alive and well? Hell yes.. Dr Stopek took the money and ran it seems as she moved on after silencing the PS Targeting data as much and long as possible ...
For those that don't know IDEXX has presence in Maine / Missouri and worked with the late Dr Phil Thorpe
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Authors Liang Y, Besch-Williford C, Cook MT, Belenchia A, Brekken RA, Hyder SM
Received 14 March 2019
Accepted for publication
18 July 2019
Published
31 July 2019
Volume 2019:11 Pages 249â??259
DOI https://doi.org/10.2147/BCTT.S208706
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Melinda Thomas
Peer reviewer comments 4
Editor who approved publication: Professor Pranela Rameshwar
APR-246 alone and in combination with a phosphatidylserine-targeting antibody inhibits lung metastasis of human triple-negative breast cancer cells in nude mice
Yayun Liang,1
Cynthia Besch-Williford,2
Matthew T Cook,3
Anthony Belenchia,4
Rolf A Brekken,5
Salman M Hyder1
1Department of Biomedical Sciences and Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA;
2IDEXX BioAnalytics, Columbia, MO, USA;
3Department of Biology, Washburn University, Topeka, KS, USA;
4Department of Nutrition and Exercise Physiology and Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA;
5Hamon Center for Therapeutic Oncology Research and Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
Conclusion
In conclusion, our study provides a strong rationale for using a therapy regimen that combines APR-246 and 2aG4 to treat and prevent metastatic breast cancer in lungs originating from mtp53-expressing TNBC cells. The former targets and activates mtp53, likely inducing apoptosis of metastatic cells, while the latter disrupts tumor blood vessels and may also activate an immune response in tissues. Our in vivo animal studies showed no signs of toxicity with any of the regimens tested, leading us to propose that such therapy could prove beneficial and safe for women with TNBC, who currently have few effective treatment options. Furthermore, because the p53 mutation is common in other types of cancer and angiogenesis is essential for the spread of all types of tumors,45,46 we contend that our findings support further study of APR-246 and 2aG4 for treating human TNBC, as well as other forms of cancer.47,48
https://www.dovepress.com/apr-246-alone-and-in-combination-with-a-phosphatidylserine-targeting-a-peer-reviewed-fulltext-article-BCTT
integrated crop solutions – the combination of high value seeds and chemical and biological crop protection
Remember, the path to profitability on chart link below is stretched out as the Rev estimates of the contracts announced (2 weeks about AFTER the 3 week early surprise year end earnings PR (so Avid BOD did not have to report AFTER new contracts were announced which makes it impossible to have kept their $64-67M estimate)) did not take into consideration that Avid Bioservices is at full capacity ..
Dr Mackey in deed made out on breadcrumb options with that early reporting of year end BEFORE new contracts announced but those buying low continue to buy low ..for the time being
Someone trying to make it look like the road to profitability is not close : )
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Avid Bioservices, Inc.'s (NASDAQ:CDMO) Path To Profitability
Simply Wall St.
July 31, 2019, 3:52 PM UTC
Avid Bioservices, Inc.'s (NASDAQ:CDMO): Avid Bioservices, Inc., a contract development and manufacturing organization, provides process development and Current Good Manufacturing Practices (CGMP) commercial manufacturing services focused on biopharmaceutical products derived from mammalian cell culture for biotechnology and pharmaceutical companies. The US$378m market-cap company announced a latest loss of -US$9.7m on 30 April 2019 for its most recent financial year result. As path to profitability is the topic on CDMO’s investors mind, I’ve decided to gauge market sentiment. Below I will provide a high-level summary of the industry analysts’ expectations for CDMO.
According to the 3 industry analysts covering CDMO, the consensus is breakeven is near. They expect the company to post a final loss in 2020, before turning a profit of US$8.8m in 2021. CDMO is therefore projected to breakeven around 2 years from today. In order to meet this breakeven date, I calculated the rate at which CDMO must grow year-on-year. It turns out an average annual growth rate of 76% is expected, which is extremely buoyant. Should the business grow at a slower rate, it will become profitable at a later date than expected.
NasdaqCM:CDMO Past and Future Earnings, July 31st 2019
Given this is a high-level overview, I won’t go into details of CDMO’s upcoming projects, though, take into account that by and large a biotech has lumpy cash flows which are contingent on the product type and stage of development the company is in. This means that a high growth rate is not unusual, especially if the company is currently in an investment period.
Before I wrap up, there’s one aspect worth mentioning. CDMO has managed its capital prudently, with debt making up 0.2% of equity. This means that CDMO has predominantly funded its operations from equity capital,and its low debt obligation reduces the risk around investing in the loss-making company.
Next Steps:
There are too many aspects of CDMO to cover in one brief article, but the key fundamentals for the company can all be found in one place – CDMO’s company page on Simply Wall St. I’ve also put together a list of relevant aspects you should further examine:
Valuation: What is CDMO worth today? Has the future growth potential already been factored into the price? The intrinsic value infographic in our free research report helps visualize whether CDMO is currently mispriced by the market.
Management Team: An experienced management team on the helm increases our confidence in the business – take a look at who sits on Avid Bioservices’s board and the CEO’s back ground.
https://finance.yahoo.com/news/avid-bioservices-inc-nasdaq-cdmo-155255237.html
Avid BOD have not updated shareholders yet on any communications with their decision to allow Oncologie to advance PS Trgetinh IP / Biomarkers etc and now with ongoing FBI investigation regarding IP related to cancer researchers...updates should be coming
Flipped PS travels the bloodstream and breaks the blood brain barrier ....looks like Independent BOD Catherine Mackey will be confronted with questions
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Regulating the interaction between tam ligands and lipid membranes with exposed phosphatidylserine
Inventor
Greg E. Lemke
Lawrence C. Fritz
Benedikt Vollrath
Carla V. Rothlin
https://patents.google.com/patent/WO2014018535A1/ar
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Lipid membranes with exposed phosphatidylserine as tam ligands, use for treating autoimmune diseases
Inventor
Greg E. Lemke
Lawrence C. Fritz
Benedikt Vollrath
Carla V. Rothlin
Current Assignee Salk Institute for Biological Studies
Celldex Therapeutics Inc
https://patents.google.com/patent/EP3184121A2/en
_____________________
Patents Assigned to AMPRION, INC.
DETECTION OF MISFOLDED TAU PROTEIN
Publication number: 20180335438
Abstract: Methods and kits are provided for amplifying and detecting misfolded tau protein from samples, for example, from patients having tauopathies such as Alzheimer's Disease, Progressive Supranuclear Palsy, and the like.
Type: Application
Filed: May 16, 2018
Publication date: November 22, 2018
Applicants: Amprion, Inc., BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM
Inventors: Claudio Soto-Jara, Russell M. Lebovitz, Benedikt K. Vollrath, Mohammad Shahnawaz, Nicolas Mendez Dinamarca
DETECTION OF MISFOLDED PROTEINS
Publication number: 20180196069
Abstract: Methods and kits are provided for amplifying and detecting misfolded proteins from samples, for example, from patients having Alzheimer's Disease, Parkinson's Disease, and the like. For example, a method for determining a presence of soluble, misfolded protein in a sample may include contacting the sample with a monomeric, folded protein to form an incubation mixture; conducting an incubation cycle two or more times effective to form an amplified portion of misfolded protein; incubating the incubation mixture effective to cause misfolding and/or aggregation of at least a portion of the monomeric, folded protein; physically disrupting the incubation mixture effective to break up at least a portion of any protein aggregate present; and determining the presence of the soluble, misfolded protein in the sample by detecting at least a portion of the soluble, misfolded protein. The monomeric, folded protein and the soluble, misfolded protein may exclude prion protein (PrP) and isoforms thereof.
Type: Application
Filed: March 8, 2018
Publication date: July 12, 2018
Applicants: Board of Regents of the University of Texas System, Amprion, Inc.
Inventors: Claudio Soto-Jara, Russell M. Lebovitz, Benedikt K. Vollrath, Mohammad Shahnawaz
Detection of misfolded amyloid beta protein
Patent number: 9910049
Abstract: Methods and kits are provided for amplifying and detecting A? proteins from samples, for example, from patients having Alzheimer's Disease. For example, a method for determining a presence of a soluble, misfolded A? protein may include contacting the sample with a monomeric, folded A? protein to form an incubation mixture; conducting an incubation cycle two or more times on the incubation mixture effective to form an amplified portion of misfolded A? protein; incubating the incubation mixture effective to cause misfolding and/or aggregation of at least a portion of the monomeric, folded A? protein; physically disrupting the incubation mixture effective to at least partly de-aggregate at least a portion of a misfolded A? aggregate present; and determining the presence of the soluble, misfolded A? protein in the sample by detecting at least a portion of the amplified portion of misfolded A? protein.
Type: Grant
Filed: September 11, 2015
Date of Patent: March 6, 2018
Assignees: AMPRION, INC., THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM
Inventors: Claudio Soto Jara, Mohammad Shahnawaz, Russell M. Lebovitz, Benedikt K. Vollrath
https://patents.justia.com/assignee/amprion-inc
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Exosomes help track effectiveness of experimental Parkinson's disease drug
March 21, 2019
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This study confirms the value of exosomes as an additional analytical tool to show target engagement in clinical trials. The investigators are optimistic about future work to examine how exosomes could help speed up validation in clinical trials of potential new drugs for PD, Alzheimerâ??s disease, and other neurological disorders.
https://www.nia.nih.gov/news/exosomes-help-track-effectiveness-experimental-parkinsons-disease-drug
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NIA Small Business funding seeks to find blood-based diagnostic for Alzheimerâ??s disease
July 30, 2019
A test for early detection of Parkinsonâ??s disease, which recently received Breakthrough Device Designation by the FDA, may have the potential to become an early measure for Alzheimerâ??s disease as well. With NIH funding that includes Small Business grants from NIA, Amprion, a California-based biotech company, has developed a technology to detect very small amounts of proteins in the cerebrospinal fluid and bloodstream that could be used to detect the diseases.
Having an effective, accurate, and easy-to-administer test for diagnosing Alzheimerâ??s and Parkinsonâ??s diseases is crucial to help develop treatments and potentially find cures for these diseases. Currently, the use of biomarkers for Alzheimerâ??s disease in a clinical setting, such as a doctorâ??s office, is limited.
The FDAâ??s Breakthrough Devices Program is designed to speed up development, assessment, and review of medical devices that could provide more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions. The FDA designation puts Amprionâ??s Protein Misfolding Cyclic Amplification (PMCA) system a step closer to approval for early detection of the alpha-synuclein protein, which would help diagnose Parkinsonâ??s disease. Amprion anticipates market rollout within 18 months. Ongoing efforts funded by NIA grants are dedicated to similarly detecting proteins associated with Alzheimerâ??s disease.
The ongoing NIA funding is specific to detecting traces of amyloid and tau aggregates. Amprion hypothesizes that detection of misfolded amyloid and tau oligomers circulating in cerebrospinal fluid and blood may be the basis for an early Alzheimerâ??s biomarker. With the funding, the company plans to adapt the PMCA technology for specific and highly sensitive detection in human cerebrospinal fluid and blood plasma, perform studies of specificity and sensitivity using a large number of samples from people with Alzheimerâ??s, and evaluate the utility of PMCA for monitoring Alzheimerâ??s disease progression.
The PMCA technology has been under development, with the support of several NIH grants from NIA, the National Institute of Neurological Disorders and Stroke, and the National Institute of Allergy and Infectious Diseases, for the past 15 years. PMCA, also known as RT-QuIC, is a platform technology to detect misfolded protein oligomers implicated in various neurodegenerative diseases, including Alzheimer's, Parkinson's, and prion diseases. The technique harnesses the way proteins misfold, aggregate, and spread in the brain and then amplifies their quantity so small amounts can be found in biological fluids. The PMCA/RT-QuIC assay to detect misfolded prion protein is already being used to diagnose prion diseases. Amprion was founded, with funding from several Small Business Innovation Research (SBIR)/Small Business Technology Transfer (STTR) grants, to facilitate the commercialization of these assays.
This research is funded in part by NIA grants R42AG049562 and R42AG058333.
https://www.nia.nih.gov/news/nia-small-business-funding-seeks-find-blood-based-diagnostic-alzheimers-disease
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Flipped PS travels the bloodstream and breaks the blood brain barrier ....looks like Independent BOD Catherine Mackey will be confronted with questions
No Clay to update on Avid CDMO chart?
It is only a matter of time before the real breakout comes our way
In the mean time back in 2011-2013 when Interim President CEO Rick Hancock and new BOD Catherine Mackey sitting together over at Althea as they awaited the big Japanese Ajinomoto buyout, maybe Hancock tells Mackey they will do it again in a couple years so she profits big on $6 options
Interesting ties though to CAR-T and also to Cour Pharmaceuticals with their Immune Modifying Microparticles
Cour would have to pay hefty IP royalty rights with the targeting of negatively charged particles going on in places
Daniel R Getts in Australia ... I imagine the list of meetings that Peregrine had in Australia could really stir things up around here
there are about 3000 retail shareholders...
I wonder which CDMO is in play for Avid Bioservices to pick up
Ampersand Capital Partners ties to Avid BOD just picked up Vibalogics and Vibalogics giving such a demand that should place Avid at $20+ once they get their act together or more cheap options get handed out
PS Targeting IP not even reflected in the current share price
Latest List of Letter Writers:
1. golfho
2. eb0783
3. trader
4. peregr
5. biopharm
6. Mauiziomh
7. unpathedhaunt
8. Wernaaa
9. sunstar
10. Jerry200
11. patientlywaiting
12. rjurko
13. atonewith PPHM
14. swg_tdr
15. bfiest
16. shipbuilder
17. JJ1223
18. Mmignot
18 is not enough…
True, though all Peregrine Pharmaceuticals ...now Avid Bioservices shareholders should expect to have BOD members that maximize share price via the business model
Avid BODs elected to place PS Targeting IP assets / biomarker data exosomes etc etc into others hands
It may be time for all those shareholder letters to also be sent to Dr Mackey and as an independent Director she would have the fiduciary duty to take proper steps in verifying what was completed in the past ....(because future buyout depends on it) and ask her peers
" ..with the contracts and profitability to Avid, why would we elect to pick up breadcrumbs vs splitting off the IP side of the house and make Peregrine the subsidiary with separate stock symbol and all goes as planned with Avid CDMO till they maximize a deal with the IP"
"...I know Biomarkers and I am on the Board at Poseida where their IP may be threatened by PS Targeting IP research/ data etc ....Novartis has much invested in CAR-T and Poseida could utilize the PS Targeting IP and ..."
My question to Dr Mackey..
Ask the BOD if there are any clauses where if Oncologie Inc withers away the IP ...do we Avid BOD have rights to pull it back away from Oncologie Inc ?
If not....this is as bad as not placing full criminal blame upon CSM for sabotage
For those that do not want to maximize shareholder value....Why not
There is a reason why Dr Mackey is here and I am not convinced fully just yet
True, yet I also see this as an opportunity for such a RD diva into CAR-T Cytokine Storms for PS Targeting to shine (or Dr Mackie is brought in to quietly diminish full PS Targeting IP profits as CDMO profits keep many quiet
As said before.... PROMISING CDMO contracts for exchange of what ?? is more likely the tactic being played out
Mackey is pure R/D from Pfizer days and if she seen the research data / Biomarkers all from PS Targeting ...those profits FAR outweigh CDMO contract profits
She is there for a reason and we shall see
Not convinced just yet about Dr Catherine Kitty Mackey
She sure seems like an odd pick for a up and coming major CDMO, since R/D is more her expertise especially CAR-T cell therapy
Unless ...like some suspect, the IP assets are MUCH more valuable than John Springs Stafford told shareholders
CYprus CEO
BOD Jan 2019 Poseida Therapeutics with IP ties to TeneoBio
Much more ...and clearly not Independent BOD to Avid shareholders unless she is presented with facts and responds to adhere to fiduciary duties to Avid shareholders
Maybe we should ask some close ties to Dr Mackey and not so Independent it seems to me when she is aligned with past of CEO Rick Hancock
Time will tell and Poseida Therapeutics REQUIRES PS Targeting IP assets to limit Cytokine Storms ...heck, even Dr Jedd Wolchok can see that!
Interesting times for Kitty as she has funds and friends tied to CAR-T advancement elsewhere
Enough for now
Avid Bioservices receiving royalties milestones etc etc etc from PS Targeting IP from Oncologie Inc and we wait for exosomes news out of UTSWM and any other biomarker driven developments that require PS Targeting
Many thought it was nonsense in how corrupt Big Pharma can be and how some stop at nothing to control drug development such as PS Targeting IP
PS Targeting has been in the works for many years starting with the late Dr Phil Thorpe and many twists and turns since ... we have had multiple sabotaged like trials, have had Dr Jack West hit piece articles against Peregrine to Ex Bristol Myer Squibb Robert H Schwartz that wrote the 'throw in the towel ..' hit piece on Peregrine to Jim Cramer want a be Adam F that had many a hit piece articles on Peregrine ... leading to historical control arm Docetaxel that Ex CEO Steve King publicly had words of disbelief ...
So so much more ....and many wondered what federal investigations were ongoing and now, they are dropping left and right from key institutions that had access to PS Targeting research data
I know am bewildered in how John Springs Stafford could have been left out of the loop ...along with Oncologie Inc backers ...especially with Federal Investigations active
US President Trump officially says they will cure cancer / Alzheimer's etc ....same positive remarks from Joe Biden ...and I say it is no coincidence that for the first time in history the confidence is building
IIS building in Avid as well... as this is truly not even close to the trading like that of Peregrine past.
Lots of MOA sound similar to that of Bavituximab / PS Targeting
Could a select few BPs corner get to market first with PS Targeting and promise CDMO astronomical type CDMO business based upon PS Targeting IP asset research etc ?
______
July 11, 2019
Report: Cornell’s ties to Qatar and China under federal investigation
The Department of Education is alleging that Cornell University has failed to disclose foreign gifts and contracts from Qatar and China, according to a report by the Associated Press.
The department, through letters to university presidents, alleged that Cornell, along with Texas A&M, Georgetown University and Rutgers University, did not tell federal officials about particular gifts and contracts. Two universities’ letters have been released publicly, while two more are expected to be released sometime next week.
Cornell spokesman John Carberry shared the following statement: “On July 3, Cornell University received a letter from the Department of Education, requesting records related to previously submitted federally required reports. Cornell takes our reporting requirements seriously. We are currently reviewing the request and plan to fully cooperate with federal officials in this effort.”
The University has received over $65 million in contracts and gifts from Qatar between 2012 and 2018, according to data aggregated by the Department of Education. Universities are required to report contracts and gifts greater than $250,000 per year. Cornell also notes that it has a “significant international educational presence, including Weill Cornell Medical College’s campus in Doha, Qatar,” in its 2017 990 tax filing.
“Weill Cornell Medicine – Qatar has trained and graduated hundreds of young physicians from the Middle East, Asia and many other countries (including the U.S.), enabling the ongoing transformation of patient care, biomedical research and quality of life in the region and around the world,” continued Carberry’s statement.
Leaderboard 2
Cornell has also received $12.5 million worth of contracts and gifts based in China. Over $5 million of that money was from contracts with Huawei, a technology company listed by the federal government as one that is denied sensitive technology because it is a danger to national security. The $5.3 million payment, spread over two research contracts in 2017, was the largest payout to an American university in the last six years, the Cornell Sun reported.
Cornell’s Qatar campus was established in January 2001, and has since operated in a relationship with Weill Cornell Medicine, which is based in Cornell’s New York City campus. It is one of six U.S. schools that have branches in Qatar.
________________
July 11, 2019
The Cytokine TNF Promotes Transcription Factor SREBP Activity and Binding to Inflammatory Genes to Activate Macrophages and Limit Tissue Repair
Anthony Kusnadi 6
Sung Ho Park 6
Ruoxi Yuan
Tania Pannellini
Eugenia Giannopoulou
David Oliver
Theresa Lu
Kyung-Hyun Park-Min
Lionel B. Ivashkiv 7
Published:July 11, 2019
Highlights
•
TNF induces late-phase activation of SREBP2 and cholesterol genes in macrophages
•
SREBP2 binds and activates inflammatory target genes in TNF-stimulated macrophages
•
Inhibition of the TNF-SREBP axis promotes M2-like polarization and wound healing
•
The TNF-SREBP axis is an attractive therapeutic target for promoting tissue repair
Summary
Cytokine tumor necrosis factor (TNF)-mediated macrophage polarization is important for inflammatory disease pathogenesis, but the mechanisms regulating polarization are not clear. We performed transcriptomic and epigenomic analysis of the TNF response in primary human macrophages and revealed late-phase activation of SREBP2, the master regulator of cholesterol biosynthesis genes. TNF stimulation extended the genomic profile of SREBP2 occupancy to include binding to and activation of inflammatory and interferon response genes independently of its functions in sterol metabolism. Genetic ablation of SREBP function shifted the balance of macrophage polarization from an inflammatory to a reparative phenotype in peritonitis and skin wound healing models. Genetic ablation of SREBP activity in myeloid cells or topical pharmacological inhibition of SREBP improved skin wound healing under homeostatic and chronic inflammatory conditions. Our results identify a function and mechanism of action for SREBPs in augmenting TNF-induced macrophage activation and inflammation and open therapeutic avenues for promoting wound repair.
https://www.cell.com/immunity/pdfExtended/S1074-7613(19)30275-4
What has David Malek been doing with Pivotal Bioventures to advance PS Targeting / Biomarkers fully? Hopefully the right party Can Fite Biopharma or maybe aMoon Fund will reveal how big they think PS Targeting is
Review the posts there is no FBI conspiracy
The fact is FBI active investigations are on going
61 Institutions including MD Anderson 21 MDs/research scientists etc is the tip of the iceberg
How many hundreds of emails are under watch / review
PS Targeting IP / Biomarkers astronomical in view of Big Pharma? Hell yes
How far will some go? To the depths of Fargo and this river runs deeper than most imagine
I guess cures for cancer and related IP for certain paths are causing dominos to fall
Suzanne Eaton spouse Tony Hyman had very close research tying into cell polarity, where flipped PS begins the move to the outer cell membrane and resulting in net negative charge
Now since we know FBI had visited at least 61 sites, one being MD Anderson to have 21 research scientist / MDs etc on watch work home emails etc, in combination with sabotage of PS Targeting phase II trial in Fargo ND Clinical Supplies Management Jeanette Bleecker as the CEO Gerald Finken took over the sabotage job and paid off via CSM expansion? by hedge fund ...etc etc we know must ask all the tough questions
How many emails were being tracked ...my guess closer to a thousand
___
Tony Hyman had been involved for many years this one from 2005
Gordon Research Conference
https://www.grc.org/mechanisms-of-cell-signalling-conference/2005/
____
..to 2007
The Rho GTPase-activating proteins RGA-3 and RGA-4 are required to set the initial size of PAR domains in Caenorhabditis elegans one-cell embryos
Stephanie Schonegg,* Alexandru T. Constantinescu, Carsten Hoege, and Anthony A. Hyman
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany
*To whom correspondence should be addressed. E-mail: ed.gbc-ipm@ggenohcs
Communicated by Kai Simons, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany, July 27, 2007.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986598/#__ffn_sectitle
____
There are too many others to list at this time but the passing of many prominent research scientists a coincidence? Maybe as much as a hedge fund hiring out some to down play the important of PS Targeting
What would the late Dr Phil Thorpe say it he was still here? As David Carbone father Paul Carbone first got laughed at for combination chemotherapy...we are at the next stage of the paradigm shift and it is PS Targeting that is allowing for much of the protein pathways to be revealed via live 3D imaging of a single cell as MOAs of hundreds of drugs will be revealed
How valuable is PS Targeting? As Steve King said...astronomical
Let the investigations begin...
http://www.bbc.com/news/uk-wales-south-east-wales-35797148
Parsa ... Thorpe....how many more are tied to disruptive paradigm shifts in biotech and all of a sudden, pass on...
Peregrine Pharmaceuticals and PS Targeting is as disruptive as it gets
Steve Schwartz hasn’t updated his target. Last record was 3/13/18 when First Analysis initiated with a $4 target.
Cheynew, I believe this is why Avid BOD hinted at "another expansion" possibly via buying someone out more likely
The news this morning now should fill their extra capacity which was already having trial runs for FDA compliance it seems and remember...that $67 Million upper estimate was not based upon this news which may be why they announced much earlier than ever before (Avid CDMO would have a much much higher revenue estimate if they announced as they normally would and profitability here NOW)
Looks like they are trying ever so gently to keep the pps down and keep the IP assets of PS Targeting research / biomarker / etc data locked up
Did Avid even mention Oncologie Inc got $80 Million for trials ? How much of that is reflected in Avid CDMO share price? Zero
Italian researchers well aware of Phosphatidylserine as Biomarkers ...the question is what is Oncologie CEO Laura Benjamin doing with all this research
Avid Bioservices set to receive royalties milestones etc etc based upon PS Targeting / Biomarkers etc
Also look how some authors such as Lamya Garabet from 2017 to 2019, realizing how it is due to flipped PS to find where the trouble begins with ITP Immune Thrombocytopenia
______
July 7, 2019
Searching for Potential Lipid Biomarkers of Parkinson’s Disease in Parkin-Mutant Human Skin Fibroblasts by HILIC-ESI-MS/MS:
Preliminary Findings
Cosima D. Calvano 1,2,*,
Giovanni Ventura 1,
Anna Maria M. Sardanelli 3,4,*,
Laura Savino 3,
Ilario Losito 1,2,
Giuseppe De Michele 5,
Francesco Palmisano 1,2 and
Tommaso R. I. Cataldi 1,2
1 Dipartimento di Chimica, Universita` degli Studi di Bari Aldo Moro, via Orabona 4, 70126 Bari, Italy
2 Centro Interdipartimentale SMART, Universita` degli Studi di Bari Aldo Moro, via Orabona 4, 70126 Bari,
Italy
3 Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”,
70100 Bari, Italy
4 Department of Medicine, Campus Bio-Medico University of Rome, 00128 Roma, Italy
5 Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples
Federico II, 80131 Naples, Italy
*
Correspondence:cosimadamiana.calvano@uniba.it(C.D.C.);annamaria.sardanelli@uniba.it(A.M.S.)
Received: 29 May 2019;
Accepted: 5 July 2019;
Published: 7 July 2019
https://res.mdpi.com/ijms/ijms-20-03341/article_deploy/ijms-20-03341.pdf?filename=&attachment=1
_____
PROFILING CIRCULATING MICRORNAS IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA (ITP) TO EXPLORE THE ROLE OF MICRORNAS AND POSSIBLE BIOLOGICAL PATHWAYS INVOLVED IN THE PATHOGENESIS OF ITP
Author(s):
Lamya Garabet ,
Waleed Ghanima ,
Anbjørg Rangberg ,
Raul Teruel-Montoya ,
Constantino Martinez ,
James B. Bussel ,
Per Morten Sandset ,
Christine Monceyron Jonassen
EHA Library. Garabet L.
May 18, 2017; 181210; E1434
https://library.ehaweb.org/eha/2017/22nd/181210/lamya.garabet.profiling.circulating.micrornas.in.patients.with.immune.html
____
Increased microvesicle-associated thrombin generation in patients with immune thrombocytopenia after initiation of thrombopoietin receptor agonists
Lamya Garabet,
Waleed Ghanima,
Marit Hellum,
Per Morten Sandset,
James B. Bussel,
Hoa Tran &
Carola E. Henriksson
show less
Received 11 Apr 2019,
Accepted 28 Jun 2019,
Published online: 07 Jul 2019
Abstract
Immune thrombocytopenia (ITP) patients have thrombocytopenia and increased bleeding risk, but, conversely, they also have increased thrombotic risk which appears to be exacerbated by thrombopoietin-receptor agonist (TPO-RA)-treatment. Microvesicles (MVs) released from activated/apoptotic cells are prothrombotic due to exposure of phosphatidylserine (PS) and tissue factor (TF). MVs are increased in ITP patients, but their prothrombotic effect, before and during treatment with TPO-RAs, is unclear.
We studied the effect of TPO-RAs on the procoagulant activity of MVs in 11 ITP patients, before, and two and six weeks after initiation of treatment, and in 15 healthy controls. MV-associated PS-activity, TF-activity and the capacity of isolated MVs and plasma to generate thrombin in a phospholipid-dependent manner were measured.
Before treatment with TPO-RAs, prothrombotic markers in ITP patients were comparable to levels found in healthy controls. After both two and six weeks of TPO-RA-treatment, ITP patients had higher MV-associated PS-activity and phospholipid-dependent thrombin generation in plasma than controls. In addition, ITP patients had increased phospholipid-dependent MV-associated thrombin generation two weeks after initiation of TPO-RA-treatment compared with controls and pre-treatment levels. MV-associated TF-activity was low in controls and in ITP patients before and after initiation of TPO-RA-treatment.
In conclusion, TPO-RAs increase phospholipid-dependent MV-associated thrombin generation in ITP patients. This could contribute to or exacerbate a pre-existing hypercoagulable state. Phospholipid-dependent thrombin generation generated by isolated MVs, or measured directly in plasma, may be potential tools that could help in the risk-assessment of future thromboembolic events in ITP patients, both before and after initiation of TPO-RA-treatment.
https://www.tandfonline.com/doi/full/10.1080/09537104.2019.1639655?scroll=top&needAccess=true
_________
2-2016: Rutgers' Dr. Raymond Birge's relationship with Peregrine & UTSW's Dr. Rolf Brekken and his 2-26-16 article, “Phosphatidylserine is a Global Immunosuppressive Signal in Efferocytosis, Infectious Disease, and Cancer” http://tinyurl.com/z5d9qt9
..
....
In full expansion to current facilities the maximum annual revenue we could produce if we were 100% utilized is $200m. The upper end of the values for CDMOs is 7 X revenue. That's a market cap of $1.4b. That's a pps of $23.
....
I haven't laughed so hard since I heard buyout at $5 : )
...and I thought these new BODs were good for us and all you believe is a buyout at $8
The ice Berg has not even been approached to start chipping away at the true value of PS Targeting where IP assets royalties milestones etc etc we don't know what happens that fall to Avid Bioservices
Who knows... Maybe Oncologie gets busted for some clause in the contract of the IP asset agreement where they are not advancing the IP as they should and it reverts back to CDMO
Interesting times
Could we get to $7?
Well absolutely
That is like saying Cancer treatment does not require PS Targeting
It had always been about the IP and some will do just about anything to control it
DNA Forensics benefiting quite well from it ...as others
Interesting how Laura E Benjamin bringing in Eli Lilly employees she can trust and is it possible Peregrine had a list of partners at one point and some had to be axed due to FBI Investigations / IP patent info /research data / being sold to parties with ulterior motives etc and Eli Lilly was one of the groups they trusted...hmm, or I should say the lesser of other evils?
Interesting times ...but it will all surface
___
Targeting Tumor Associated Phosphatidylserine with New Zinc Dipicolylamine-Based Drug Conjugates.
Liu YW, et al. Bioconjug Chem.
2017.
Authors
Liu YW1, Shia KS1, Wu CH1, Liu KL1, Yeh YC1, Lo CF1, Chen CT1, Chen YY1, Yeh TK1, Chen WH1, Jan JJ1, Huang YC1, Huang CL1, Fang MY1, Gray BD2, Pak KY2, Hsu TA1, Huang KH1, Tsou LK1.
Author information
1
Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes , Miaoli 35053, Taiwan, ROC.
2
Molecular Targeting Technologies, Inc. , West Chester, Pennsylvania 19380, United States.
Citation
Bioconjug Chem. 2017 Jul 19;28(7):1878-1892. doi: 10.1021/acs.bioconjchem.7b00225. Epub
2017 Jun 19.
Abstract
A series of zinc(II) dipicolylamine (ZnDPA)-based drug conjugates have been synthesized to probe the potential of phosphatidylserine (PS) as a new antigen for small molecule drug conjugate (SMDC) development. Using in vitro cytotoxicity and plasma stability studies, PS-binding assay, in vivo pharmacokinetic studies, and maximum tolerated dose profiles, we provided a roadmap and the key parameters required for the development of the ZnDPA based drug conjugate. In particular, conjugate 24 induced tumor regression in the COLO 205 xenograft model and exhibited a more potent antitumor effect with a 70% reduction of cytotoxic payload compared to that of the marketed irinotecan when dosed at the same regimen. In addition to the validation of PS as an effective pharmacodelivery target for SMDC, our work also provided the foundation that, if applicable, a variety of therapeutic agents could be conjugated in the same manner to treat other PS-associated diseases.
Avid Bioservices manufactures for Halozyme re: PEGPH20 and ENHANZE and some more research out on PEGPH20 which further should help lock up Avid manufacturing contracts
The question is as PS Targeting IP assets remodels the TME ( Tumor Microenvironment) and when it comes to remodeling the TME the IP held by Peregrine ...now Oncologie via a John Springs Stafford act, should raise MANY questions by all
I like how CDMO is on the rise but is it possible that Avid being guaranteed manufacturing rights in exchange for something else ...
Looks like Johnson / Johnson just poached Halozyme employee Sheryl Apostol Garrovillo who is well aware the TME
Johnson and Johnson just may like the way Anti-PS changes the TME and and I imagine JnJ would not be pleased if Oncologie was blocking them from IO combos with Bavi etc ...
Merck doesn't seem to have any problems using Keytruda with Bavi
______
Remodeling the Tumor Microenvironment Sensitizes Breast Tumors to Anti- Programmed Death-Ligand 1 Immunotherapy
Renee Clift, Jennifer Souratha, Sheryl A. Garrovillo, Susan Zimmerman and Barbara Blouw
Abstract
Immunotherapies targeting immune checkpoint inhibitors have changed the landscape of cancer treatment, however, many patients are resistant or refractory to immunotherapy. The sensitivity of tumor cells to immunotherapy may be influenced by hyaluronan (HA) accumulation in the tumor microenvironment (TME). Enzymatic degradation of HA by pegvorhyaluronidase alfa (PEGPH20; PVHA) remodels the TME. This leads to reduced tumor interstitial pressure and decompressed tumor blood vessels which are both associated with increased exposure of tumor cells to chemotherapy drugs. Here, we demonstrate pegvorhyaluronidase alfa increased the uptake of anti-programmed death-ligand 1 (PD-L1) antibody in HA-accumulating animal models of breast cancer. The increased levels of anti-PD-L1 antibody were associated with increased accumulation of T-cells and natural killer cells, and decreased myeloid-derived suppressor cells. PD-L1 blockade significantly inhibited tumor growth when combined with pegvorhyaluronidase alfa, but not alone. Our results suggest that pegvorhyaluronidase alfa can make HA-accumulating tumors sensitive to anti-PD-L1 immunotherapy.
Received September 28, 2018.
Revision received January 22, 2019.
Accepted June 24, 2019.
______
Experience
Senior Associate Scientist
The Janssen Pharmaceutical Companies of Johnson & Johnson
May 2019 â?? Present 3 months
3210 Merryfield Row, San Diego, CA 92121
Halozyme Therapeutics, Inc.
5 years
Senior Histopathology Technician II
January 2018 â?? April 2019 1 year 4 months
11388 Sorrento Valley road, San Diego, CA 92121
...
...
Responsible for hands-on implementation of the histology laboratory providing high quality histology services
Prepare tissues for histological evaluation including use of immunohistochemistry staining techniques to support preclinical development and collaborations
Representative of histology group for Protocol Reviews
Team lab. Captain for Research Operational Team
Support vivarium necropsy on large studies and train other associates on optimal tissue embedding techniques for optimal histology read out
Develop, optimize antibody, cross-reactivity studies and validate different immunohistochemistry techniques and staining methods for preclinical and clinical studies
Prepare tissues for IHC: grossing, fixing, processing, embedding, trimming and sectioning
Perform histochemistry, immunohistochemistry, immunofluorescence, FISH/ISH based assays
Perform paraffin and cryostat sectioning
Validate and troubleshoot technical problems in assay development
Maintaining inventory of paraffin blocks and slides
Archiving blocks and stain/unstained slides
Stocking, inventory and order lab supplies
Manage histo lab equipment and microscopes for routine PM services
Helps in developing multiplex staining in Leica Bond and Ventana Machine
Senior Histopathology Technician 1
May 2014 â?? January 2018 3 years 9 months
11388 Sorrento Valley Blvd
Responsible for hands-on implementation of the histology laboratory providing high quality histo services.
Prepare tissues for histological evaluation including use of immunohistochemistry staining techniques to support preclinical development and collaborations.
Representative of histology group for Protocol Reviews.
Team lab. Captain for Research Operational Team.
Support vivarium necropsy on large studies and train other associates on optimal tissue embedding techniques for optimal histology read out.
Prepare tissues for IHC: grossing, fixing, processing, embedding, trimming and sectioning.
Perform paraffin and cryostat sectioning.
Perform H&E, special staining and IHC staining as needed.
Developing a new IHC assays.
Quality control on finished slide preparations.
Maintaining inventory of paraffin blocks and slides.
Archiving blocks and stain/unstained slides.
Stocking, inventory and order lab supplies,
Manage histo lab equipment and microscopes for routine PM services.
Load slides in Leica Aperio scanner.
Doing IHC staining in Ventana machine, Leica Bond Max and Leica Bond III.
Keep_Trying, have you considered the Steve Demattos appearance at Xencor in March 2014 vs those back to back 30M share days vs timeline as Ronin appearing Jan 2017...and also the appearance of Sybille Sauter over at Halozyme with those Halo orders disappearing at such a convenient time that helped John Spring Stafford efforts to break into the BOD?
The IP lawsuit that never was PRd filed by Steve King (Peregrine) against Steve Xencor ..I mean Steve Demattos and Sybille Sauter etc becomes key info
Steve w/2 DeMattos