Inventorship of developments or discoveries first conceived and actually reduced to practice in the performance this Agreement ("Subject Inventions") will be determined in accordance with U.S. Patent Law and this Agreement. Except as stated below, all rights to Subject Inventions made solely by employees of University will belong solely to University and all rights to Subject Inventions made solely by employees of Sponsor will belong solely to Sponsor. All rights to Subject Inventions made jointly by employees of University and employees of Sponsor and any developments or discoveries conceived and actually reduced to practice as part of the Investigational New Drug work described in Exhibit A, Paragraph 2A and 2B, will belong jointly to University and Sponsor. To the extent that Sponsor pays all direct and indirect costs set forth in Article 4 above, and to the extent that the University is legally able, Sponsor will be granted a time-limited first right to negotiate an option or license under University's rights in any Subject Invention that belongs either solely to University or jointly to University and Sponsor. With respect to filing patents where University and Sponsor are co-inventors, University is obligated to file such patent application upon Sponsors request and will allow Sponsor the opportunity, if it so elects, to review and have right to make reasonable changes to all documents prior to filing. University will promptly disclose to Sponsor any Subject Inventions. Sponsor will hold such disclosure on a confidential basis and will not disclose the information to any third party without consent of University. Sponsor will advise the University in writing within sixty (60) days of such disclosure to Sponsor whether or not it wishes to secure an option or commercial license ("Election Period"). Sponsor will have ninety (90) days from the date of election to conclude an option or license agreement with University ("Negotiation Period"). Said license will contain reasonable terms, will require diligent performance by Sponsor for the timely commercial development and early marketing of Subject Inventions, and include Sponsor's obligation to reimburse University's patent costs for all Subject Inventions subject to the license. In the event it is necessary in the opinion of University to file any patent applications to protect a Subject Invention during the Election or Negotiation Periods, University will promptly notify Sponsor in writing of such decision and Sponsor will reimburse patent costs incurred by University during such period. If such option or license is not concluded within the Negotiation Period, neither party will have any further obligations to the other with respect to such Subject Invention. If Sponsor does not elect to secure such option or license, rights to such Subject Invention will be disposed of in accordance with University's policies, with no further obligation to Sponsor with respect to such Subject Invention. Nothing contained in this Agreement shall be deemed to grant either directly or by implication, estoppel, or otherwise, any rights under any patents, patent applications or other proprietary interests, whether dominant or subordinate, or any other invention, discovery or improvement of either party, other than the specific rights covering Subject Inventions under this Agreement.
Who owns the patent for autologous dendritic cells pulse with autologous glioblastoma peptides (which by the way it turns out BCG is used in the pulse process)?
Who owns the various patent for administration and activation of dendritic cells (including precursors) which is used in combination of the above, pulsed method? ANSWER: NWBT.
Who will own the Patent of "Combination for Checkpoint Inhibitor and Therapeutics to Treat Cancer” if granted? They both will, as will Cognate, but NWBT will have to pay licensing rights, if one goes by the agreement above. If NWBO goes bankrupt, private Cognate and RevImmune (both LP companies), will own the rights to combine DC technology with lysate with CI.
COGNATE BIOSERVICES, INC. NORTHWEST BIOTHERAPEUTICS THE REGENTS OF THE UNIVERSITY OF CALIFORNIA REVIMMUNE, INC.
AND, just incase you need to see the tumor lysate portion of the patent:
Methods for detection and treatment of neural cancers Patent number: 6558668
Abstract: The invention provides a method for inhibiting proliferation of neural cells. The neural cells can be tumor cells, glial cells, neuronal cells, and cells of the central or peripheral nervous systems. The method comprises contacting a neural cell with a molecule that disrupts the biological activity of a granulin molecule. In one embodiment, the molecule is an antibody directed against a granulin peptide. In other embodiments, the molecule is an antisense nucleotide directed against a granulin nucleic acid molecule, or a vaccine comprising a granulin peptide or a polynucleotide encoding a granulin peptide. The invention additionally provides methods for detecting and treating cancer in a neural tissue using granulin-related molecules. Also provided is a method for identifying differentially expressed gene products that are translated from mRNA species, using antibody-based screening of a cDNA expression library.
Type: Grant Filed: February 28, 2001 Issued: May 6, 2003 Assignee: The Regents of the University of California Inventor: Linda M. Liau
This application claims benefit of U.S. provisional application No. 60/185,321, filed Feb. 28, 2000, the entire contents of which are incorporated herein by reference. Throughout this application various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to describe more fully the state of the art to which this invention pertains. Some of these references are indicated by numbers in parentheses. Citations corresponding to these reference numbers can be found at the end of the specification
A pharmaceutical composition or vaccine can contain DNA encoding one or more of the polypeptides as described above, such that the polypeptide is generated in situ. As noted above, the DNA may be present within any of a variety of delivery systems known to those of ordinary skill in the art, including nucleic acid expression systems, bacteria and viral expression systems. Numerous gene delivery techniques are well known in the art, such as those described by Rolland, Crit. Rev. Therap. Drug Carrier Systems 15:143-198, 1998, and references cited therein. Appropriate nucleic acid expression systems contain the necessary DNA sequences for expression in the patient (such as a suitable promoter and terminating signal). Bacterial delivery systems involve the administration of a bacterium (such as Bacillus-Calmette-Guerrin) that expresses an immunogenic portion of the polypeptide on its cell surface or secretes such an epitope.
When DCs are pulsed with a soluble antigen, including human tumor antigen or tissue specific antigens with an adjuvant such as BCG, enhancement of MHC-class I presentation occurs. Therefore, the presence of an adjuvant such as BCG typically increases DC soluble tumor antigen processing in the MHC-class I compartment and correspondingly, activates a higher percentage of CD8+ T cells when compared to individuals administered the antigen alone.
UCLA was hired to
EXHIBIT A - STATEMENT OF WORK
This exhibit defines the nature, scope and content of work to be performed under the direction of Dr. Linda Liau, M.D., Ph.D., as Principal Investigator, working on behalf of the UNIVERSITY (UCLA) and to be delivered to the SPONSOR (NORTHWEST BIOTHERAPEUTICS, INC.) in accordance with the terms of this contract.
1. NATURE OF WORK: The University and Sponsor will jointly develop a research program defined below and also an application for a Phase II Investigational New Drug (IND) application entitled, "AUTOLOGOUS DENDRITIC CELLS PULSED WITH AUTOLOGOUS GLIOBLASTOMA TUMOR PEPTIDES," that will be submitted by the Sponsor to the Federal Drug Administration (FDA). This Phase II IND application is specifically intended to support a clinical trial performed by UCLA investigators in conjunction with the Sponsor and may not be used by the Sponsor for any other purpose unless specified and agreed to in writing by both parties.
2. SCOPE OF WORK: The work to be performed by the University falls into 3 categories:
A. Develop and validate a protocol for preparing GMP-quality suspensions of viable glioblastoma cancer cells from patients with glioblastoma, and develop protocol for preparing GMP quality peptides derived from tumor cells. Transfer the technology to Sponsor. B. Collaborate in the design and writing of sections for the IND application. C. Perform research relevant to program as defined by University and Sponsor.
3. CONTENT OF WORK:
A. Develop and validate a protocol for preparing GMP-quality suspensions of viable glioblastoma cancer cells from patients with glioblastoma multiforme and technology developed technology to Sponsor. University investigators will collect cancer specimens from the operating room and evaluate techniques for preparing purified tumor cell suspensions from these clinical samples. The goal will be to develop a GMP-quality process by which tumors recovered at the time of surgery can be placed into a transportation media and delivered to the Sponsor's cell processing facility in the form of a viable cell suspension. In addition, techniques for purifying, characterizing and culturing the tumor cell suspension after its arrival at the Sponsor's facility will be investigated. Techniques for "stripping" peptides from the surface of tumor cells and concentration of these peptides will also be developed. Results from these investigations will be formed into a detailed written protocol that will be delivered to the Sponsor. This protocol will employ GMP-quality reagents, as feasible given their current availability. The average viability, cell yield and purity of the cancer cell suspension as well as quantities of peptides "stripped" from the tumor cell surface will be reported to the Sponsor.
B. Design and write sections of the IND protocol. University investigators will, in discussion and collaboration with the Sponsor, develop a Clinical Trial Protocol and sections of a corresponding IND application for a study entitled, "PHASE II TRIAL EVALUATING AUTOLOGOUS DENDRITIC CELLS PULSED WITH AUTOLOGOUS GLIOBLASTOMA PEPTIDES FOR THE ADJUVANT TREATMENT OF MALIGNANT GLIOMA." The following sections will be prepared:
i. General Investigational Plan
ii. Investigators Brochure
iii. Detailed Protocol to include an Introduction, Objectives, Study Hypothesis and Endpoints, Treatment Plan, Pretreatment Evaluation, On Study Evaluation, Concomitant Medications, Adverse Events, and Criteria for Disease Evaluation.
iv. UCLA IRB application conforming to study guidelines.
UCLA / NORTHWEST BIOTHERAPEUTICS, INC. (AGREEMENT NO. 01082716) "DEVELOPMENT AND VALIDATION OF DENDRITIC CELLS PULSED WITH AUTOLOGOUS GLIOBLASTOMA TUMOR PEPTIDES"
EXHIBIT B - DELIVERABLES
This exhibit defines the deliverables to be provided by Linda Liau, M.D., Ph.D. as Principal Investigator, working on behalf of the UNIVERSITY, to the SPONSOR in accordance with the terms of this contract.
A. Develop and validate a protocol for preparing GMP-quality suspensions of viable glioblastoma cancer cells from patients with glioblastoma multiforme. This deliverable includes identification of reagents and resources for the IND protocol. University investigators will identify and make known to the Sponsor a list of products and manufacturers conforming to FDA-approved good manufacturing practices (GMP) as required to carry out the protocol. University investigators will prepare a detailed written protocol that will be delivered to the Sponsor. This protocol will employ GMP-quality reagents, as feasible given their current availability. The average viability, cell yield and purity of the cancer cell suspension will be reported to the Sponsor. These protocols for preparing materials for clinical trial will be transferred to Sponsor.
B. Design and write sections of the IND protocol. University investigators will, in discussion and collaboration with the Sponsor, deliver the following written sections of a Clinical Trial Protocol and corresponding IND application for a study entitled, "PHASE II TRIAL EVALUATING AUTOLOGOUS DENDRITIC CELLS PULSED WITH AUTOLOGOUS GLIOBLASTOMA PEPTIDES FOR THE ADJUVANT TREATMENT OF MALIGNANT GLIOMA."
i. General Investigational Plan
ii. Investigators Brochure
iii. Detailed Protocol to include an Introduction, Objectives, Study Hypothesis and Endpoints, Treatment Plan, Pretreatment Evaluation, On Study Evaluation, Concomitant Medications, Adverse Events, and Criteria for Disease Evaluation.
iv. UCLA IRB application conforming to study guidelines
C. Research results from sponsored research agreement. Quarterly reports will be delivered to Sponsor covering activities for the previous three months.
EXHIBIT C - PAYMENT SCHEDULE
One fourth (25% or $19,125) of total direct and indirect costs ($76,500) will be paid to the University within ten (10) days of the signing date of this agreement. One-third of the remaining balance ($19,125) will be paid to the University at quarterly intervals
AND therefore, circling back to when IND's were created, well that would be after this agreement was in place. Both IND #10206, Phase III (without TLR) and IND #11053 Phase II (with TLR) were created after 2001. All patents after this agreement were available to use. They are the same DCVax-L lysate-pulsed product, used in Phase I/II as per the SEC statement. Manufacturing difference relate to Cognate verses UCLA creating the product, and the use of TLR.
AI
