Diffusion Pharmaceuticals Inc (DFFN)

[BooDog]

From USPTO...

https://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=11,185,523.PN.&OS=PN/11,185,523&RS=PN/11,185,523


Clearly this is not a small deal. Certainly need to do a bit more dd on this but also glad I stumbled on this little bio.

Edit: Yeah, I think someone found the patent before the company had a chance to release the PR. Just released on Nov 30, 2021 but I didn't see a time.



excerpt...



SUMMARY

In one embodiment, the disclosure includes a method of treating cancer (solid tumor) in a mammal (e.g. human) comprising a) administering to the mammal a bipolar trans carotenoid salt having the formula: YZ-TCRO-ZY where: Y=a cation which can be the same or different, Z=a polar group which can be the same or different and which is associated with the cation, and TCRO=a linear trans carotenoid skeleton with conjugated carbon-carbon double bonds and single bonds, and having pendant groups X, wherein the pendant groups X, which can be the same or different, are a linear or branched hydrocarbon group having 10 or less carbon atoms, or a halogen, b) administering to the mammal radiation therapy, wherein said bipolar trans carotenoid salt is administered at time and at a dose causing increased partial pressure of oxygen in the tumor during administration of said radiation.

In a preferred embodiment, the bipolar trans carotenoid is TSC administered at a dose of 0.15-0.35 mg/kg 45-60 minutes prior to administration of said radiation therapy. In some embodiments, the subject mammal is also administered chemotherapy in addition to the radiation therapy, e.g. administering temozolomide 7 times per week for 6 weeks.

A still further embodiment of the disclosure relates to a method of treating cancer (solid tumor) in a mammal (e.g. human) comprising a) administering to the mammal a bipolar trans carotenoid salt having the formula: YZ-TCRO-ZY where: Y=a cation which can be the same or different, Z=a polar group which can be the same or different and which is associated with the cation, and TCRO=a linear trans carotenoid skeleton with conjugated carbon-carbon double bonds and single bonds, and having pendant groups X, wherein the pendant groups X, which can be the same or different, are a linear or branched hydrocarbon group having 10 or less carbon atoms, or a halogen, b) administering chemotherapy to the mammal, wherein said bipolar trans carotenoid salt is administered at a time and at a dose causing increased partial pressure of oxygen in the tumor during administration of said chemotherapy.

In a preferred embodiment, TSC administered at a dose of 0.75-2.0 mg/kg 1-2 hour prior to administration of said chemotherapy.

The cancer is selected from the group consisting of squamous cell carcinomas, melanomas, lymphomas, sarcomas, sarcoids, osteosarcomas, skin cancer, breast cancer, head and neck cancer, gynecological cancer, urological and male genital cancer, bladder cancer, prostate cancer, bone cancer, cancers of the endocrine glands (e.g. pancreatic cancer), cancers of the alimentary canal, cancers of the major digestive glands/organs, CNS cancer, and lung cancer. The chemotherapy is selected from the group consisting of alkylating agents, antimetabolites, antitumor antibiotics, topoisomerase inhibitors, and anti-microtubule agents. In some embodiments, the subject mammal is also administered radiation therapy in addition to the chemotherapy.

In an advantageous embodiment, the bipolar trans carotenoid is TSC administered at a dose of 0.75-2.0 mg/kg, 1-2 hrs. prior to administration of said chemotherapy. The chemotherapy is one or more compounds selected from the group consisting of gemcitabine, 5-fluorouracil (5-FU), irinotecan, oxaliplatin, nab-paclitaxel (albumin-bound paclitaxel), capecitabine, cisplatin, elotinib, paclitaxel, docetaxel, and irinotecan liposome.

In one embodiment, the method is administering 1.5 mg/kg TSC 45-60 minutes prior administering the chemotherapy, and administering the chemotherapy is administering gemcitabine as an IV infusion once per week for 3 weeks followed by a week of rest.

In another embodiment, 1.5 mg/kg TSC is administered 45-60 minutes prior administering the chemotherapy, and administering the chemotherapy is administering nab-paclitaxel as an IV infusion followed by gemcitabine as an IV infusion, once per week for 3 weeks followed by a week of rest.

In another embodiment, the subject disclosure relates to a method of treating a cancer of the pancreas in a mammal (e.g. human) comprising: a) administering to the mammal a bipolar trans carotenoid salt having the formula: YZ-TCRO-ZY where: Y=a cation which can be the same or different, Z=a polar group which can be the same or different and which is associated with the cation, and TCRO=a linear trans carotenoid skeleton with conjugated carbon-carbon double bonds and single bonds, and having pendant groups X, wherein the pendant groups X, which can be the same or different, are a linear or branched hydrocarbon group having 10 or less carbon atoms, or a halogen, and b) administering to the mammal chemotherapy, wherein the bipolar trans carotenoid salt is administered at a time and at a dose causing increased partial pressure of oxygen in the tumor during administration of the chemotherapy.

In an advantageous embodiment, the bipolar trans carotenoid is TSC administered at a dose of 0.75-2.0 mg/kg, 1-2 hrs. prior to administration of said chemotherapy. The chemotherapy is one or more compounds selected from the group consisting of gemcitabine, 5-fluorouracil (5-FU), irinotecan, oxaliplatin, nab-paclitaxel (albumin-bound paclitaxel), capecitabine, cisplatin, elotinib, paclitaxel, docetaxel, and irinotecan liposome.

In one embodiment, the method is administering 1.5 mg/kg TSC 45-60 minutes prior administering the chemotherapy, and administering the chemotherapy is administering gemcitabine as an IV infusion once per week for 3 weeks followed by a week of rest.

In another embodiment, 1.5 mg/kg TSC is administered 45-60 minutes prior administering the chemotherapy, and administering the chemotherapy is administering nab-paclitaxel as an IV infusion followed by gemcitabine as an IV infusion, once per week for 3 weeks followed by a week of rest.

The disclosure also relates to a method of treating a cancer of the brain (e.g. glioblastoma) in a mammal (e.g. human) comprising: a) administering to the mammal a bipolar trans carotenoid salt having the formula: YZ-TCRO-ZY where: Y=a cation which can be the same or different, Z=a polar group which can be the same or different and which is associated with the cation, and TCRO=a linear trans carotenoid skeleton with conjugated carbon-carbon double bonds and single bonds, and having pendant groups X, wherein the pendant groups X, which can be the same or different, are a linear or branched hydrocarbon group having 10 or less carbon atoms, or a halogen, and b) administering radiation therapy to the mammal wherein the bipolar trans carotenoid salt is administered at time and at a dose causing increased partial pressure of oxygen in the tumor during administration of said radiation.

When the bipolar trans carotenoid is TSC, it is administered at a dose of 0.15-0.35 mg/kg 45-60 minutes prior to said administration, typically external beam radiation therapy. In one embodiment, the radiation therapy is administering 5 times per week for 6 weeks. In another embodiment, the method includes administering chemotherapy to the mammal, e.g. administering temozolomide 7 times per week for 6 weeks.

In all of the above embodiments, advantageously the bipolar trans carotenoid salt is TSC is in the form of a composition with a cyclodextrin.