Royalty Report: Drugs, Cancer, Antibody – Collection: 273422

For the BMS Patent Rights, Licensor grants an exclusive license within the Territory to the BMS Patent Rights, to research, develop, manufacture or have manufactured, use, import, export, sell or offer for sale any and all Licensed Products, New Products and/or Improvements thereto for use in the BMS Field in the Territory.

For the T7 Technology, Licensee shall have the right, upon written notice to Licensor, to sublicense, at Licensees option, T7 Technology from Licensor non-exclusively for use with Licensed Products for human cancer uses only in the Territory.

Licensor grants a right of first negotiation and refusal during the Term of this Agreement to obtain an exclusive license to develop and commercialize Br96-Dox for use in the BMS Field in the Territory.

Br96-Dox means Doxorubicin-conjugated Br96 antibody.

Licensor has discontinued the anti-CD40 antibody program thereunder, and Licensee now wishes to continue development of anti-CD40 antibodies on its own.

As of the effective date, the Prior Agreement is terminated in its entirety.

For the Grant under Licensor CD40 Know How,  Licensor grants a license under the Licensor CD40 Know How, to research, develop, make or have made, use, import, export, sell or offer for sale, Licensed Products in the Field in the Territory.

For the Grant under Licensor CD40 Patents, Licensor grants a license under the Licensor CD40 Patents, to research, develop, make or have made, use, import, export, sell or offer for sale, Licensed Products in the Field in the Territory.

For the Grant under Licensor Patents,  Licensor grants a license under the Licensor Patents, to research, develop, make or have made, use, import, export, sell or offer for sale, Licensed Products in the Field in the Territory.

For the Right to Use Materials and Technology,  Licensor grants a license under Licensors rights in the Materials and Technology, to use the Materials and Technology in the form supplied by Licensor to Licensee under this Agreement to research, develop, make or have made, use, import, export, sell or offer for sale, Licensed Products in the Field in the Territory.

Anti-CD40 Antibody means any anti-CD40 antibody, including, without limitation, the Antibody, any variant, including, without limitation, humanized versions, or fragment, including, without limitation, single-chain versions, of any such anti-CD40 antibody, conjugates, including conjugates with radionuclides, toxins or other compounds, of any of the foregoing which, in each case, was developed by Licensor in its performance of the Prior Agreement.

Licensor CD40 Patents include, no. 60/280805 and no. 10/099,818 entitled Combination Therapy.

Licensed Product means any product containing an Anti-CD40 Antibody.

SGN-40 is a humanized monoclonal antibody that targets the CD40 antigen, which is highly expressed on most B lineage hematologic malignancies including non-Hodgkin's lymphoma, multiple myeloma and chronic lymphocytic leukemia. CD40 is also found on many types of solid tumors, including bladder, renal and ovarian cancer, and may play a role in immunologic diseases.

The following patents and patent applications, together with the know-how related thereto, constitute the BR96 sFV-PE40 Program

Patent
  
Description
License Type

Number
Number

57,444
5,491,088
  
Murine monoclonal antibody BR96, chimeric BR96 and antigen binding fragments of BR96.
Exclusive

459,354

  
Recombinant BR96 molecules having the antigen binding region of murine BR96.
Exclusive

Table 2 BR96/Drug Conjugate Program

Application
Patent
  
Description
License Type

Number
Number

353,729
5,122,368
  
Linker chemistry having an acylhydrazone linkage through C13 keto group of anthracycline to nonimmunoglobulin ligand. Linker arm also includes thioether or disulfide bond.
Partially-Exclusive for Linkers

96,628

  
Acylhydrazone linkage through C13 keto group of anthracycline to immunoglobulin. Linker arm also includes thioether or disulfide bond.
Partially-Exclusive for Linkers

824,951
5,622,929
  
Anthrecycline ligand conjugates where linkage is an acylhydrazone through C13 keto position of anthracycline. Linker also contains succinimido moiety. Chemistry is used to make first generation chiBR96-Dox.
Partially-Exclusive for Linkers

08/468,162
5,606,017
  
Anthracycline intermediate having acylhydrazone linkage through C13 keto position of anthracycline and a Michael Addition Receptor. Intermediate in conjugation used to make first generation chiBR96-Dox.
Partially-Exclusive for Linkers

08/469,840

  
Process for conjugation using intermediate above with reduced immunoglobulin to increase total drug to antibody yield. Process is used to make first generation chiBR96-Dox.
Partially-Exclusive for Linkers

62,366

  
Enzyme cleavable peptide linker for making cytotoxic drug ligand conjugates. Linkers are used to make second generation BR96-Dox.
Partially-Exclusive for Linkers

57,444
5,491,088
  
Murine monoclonal antibody BR96, chimeric BR96 and antigen binding fragments of BR96.
Exclusive

77,253

  
Immunoconjugates of murine monoclonal antibody BR96, chimeric BR96 and other recombinant antigen binding fragments. Includes single chain and bispecific recombinant constructs.
Exclusive

333,840

  
Methods of treating human carcinoma by administering murine BR96, chimeric BR96 or any recombinant antigen binding construct either by itself or conjugates with various agents. Also includes diagnostic kits.
Exclusive

459,354

  
Recombinant BR96 molecules having the antigen binding region of murine BR96.
Exclusive

08/285,936

  
Mutants of BR96 which have increased binding affinity/avidity to antigen.
Exclusive

08/487,860

  
Mutants of BR96 which have increased binding affinity/avidity to antigen.
Exclusive

60/030/367

  
Branched peptide linker for linking thiol group on targeting ligand to two or more drug moieties.
Partially-Exclusive for Linkers

5,204,244
  
Production of chimeric antibodies by homologous recombination.
Non-Exclusive

5,202,238
  
Production of chimeric antibodies by homologous recombination.
Non-Exclusive

5,482,856
  
Production of chimeric antibodies by homologous recombination.
Non-Exclusive

Table 3 G28-5 SfV/Immunotixin Program

The patents and patent applications (the “Washington Patents”), together with the know-how related thereto, sublicensed under the Washington Agreement constitute the G28-5 sFv/Immunotoxin Program. [Exclusive]

Table 4 BD1 Program

The following patents and patent applications, together with the know-how related thereto, constitute the BD1 Program

Application
Patent
Description
License Type

Number
Number

08/245,754
5,541,110
Isolated oligonucleotide sequence encoding Bryodin 1, recombinant vectors and plasmids, and transfected host cells.
Exclusive

08/597,731

Methods for the recombinant production of Bryodin 1 and Bryodin 1-ligand fusion proteins.
Exclusive

08/324,301
5,597,569
Ribosome-inactivating protein Bryodin 2 in an isolated form, linked to a ligand as a conjugate or a fusion protein, pharmaceutical compositions, nucleotide sequence, transfected host cells and recombinant production.
Exclusive

Table 5 ADEPT Program

The following patents and patent applications, together with the know-how related thereto, constitute the ADEPT Program

Application

Number
Patent
Description
License Type

(filed 5/7/96)
Number

Recombinant L49sFv-¨ lactamase fusion proteins which recognize p97 melanoma antigen and activate-cephalosporin derivatized prodrug molecules.
Exclusive

211,301
4,975,278
Methods for delivering cytotoxic agents to tumor cells by administering an effective amount of at least one antibody-enzyme conjugate, wherein the antibody is specific for a tumor associated antigen and the enzyme converts at least one weakly cytotoxic prodrug to its corresponding cytotoxic parental form; and the administration of an effective amount of the prodrug.
Non-Exclusive

Table 6 Residual Program

The following patents and patent applications, together with the know-how related thereto, constitute the Residual Program

Application
Patent
Description
License Type

Number
Number

684,759
4,935,495
Monoclonal antibodies, Fab, F(ab1)2 or Fv fragments thereof which compete for binding with L6 to its antigen.
Partially-Exclusive for Cancer

776,321
4,906,562
Methods for detecting malignancy using L6 or other monoclonal antibodies or fragments thereof which compete with L6 for binding to its antigen.
Exclusive

523,309
5,091,177
Method for reducing population of tumor cells using L6 or monoclonal antibodies which compete for binding with L6 to its antigen.
Exclusive

443,696
5,242,824
Monoclonal antibody BR64 and antigen binding fragments thereof.
Exclusive

08/726,528

Monoclonal antibodies and recombinant antigen binding molecules which recognize the G733-1 but not G733-2 antigen. Specifically BR110.
Partially-Exclusive for Cancer

527,227
5,165,922
Method of treating breast carcinoma in an unresponsive patient by first administering monoclonal antibody L6 followed by administration of a chemotherapeutic agent.
Exclusive

5,663,158
Method for treating vascular leak syndrome.
Non-Exclusive

The Residual Program also includes antibodies L6, L49, BR64, BR110, OV578.1 and OV569.1 [Exclusive]

The Field with respect to Licensed Technology for which Licensee is granted a right and license that is partially exclusive shall be

(i) if this Agreement indicates that such license is partially exclusive for linkers, all monoclonal antibody targeting applications; or (ii) if the agreement indicates that such license is partially exclusive for cancer, the treatment and diagnosis of cancer in humans. The Field with respect to Licensed Technology for which Licensee is granted a right and license that is non-exclusive shall be the treatment and diagnosis of cancer in humans. Notwithstanding the foregoing, the Field with respect to the G28-5 Licensed Technology shall be for the use of the antibody G28-5 fused with a toxin for the treatment of cancer in humans.

Licensor grants an exclusive Option for each Research Antigen designated to obtain the Exclusive License set forth during the Option Period.

If Licensee elects to exercise its option to acquire an Exclusive License with respect to a particular Research Antigen, and Licensee pays the Option Exercise Fee, then subject to the terms and conditions of this Agreement, and commencing as of the date that Licensor has received the Option Exercise Fee from Licensee, Licensor is automatically deemed to grant, and in such event hereby grants, to Licensee, on a Research Antigen-by-Research Antigen basis, a worldwide, exclusive, even as to Licensor, nontransferable, royalty-bearing license under the Licensor Technology, with the right to sublicense, to discover, have discovered, to develop, have developed, make, have made, import, have imported, export, have exported, use, sell and have sold Products directed toward such Research Antigen within the Field in the Territory.

The licensors patents and technology are for Antibodies, Research Antigens, Exclusive Antigens, and Jointly-Invented Inventions Related thereto.

Antigen means any protein, including any glyco- or lipo-protein, carbohydrate, compound or other composition, and any fragment, peptide or epitope thereof, to which an antibody hinds.

Product means any and all products where the manufacture, sale or use of such products would have constituted a misappropriation of Drug Conjugation Technology, Licensor Know-How, Improvements or New Technologies, and/or an infringement of the Licensed Patents but for the licenses granted in this Agreement.

The binding of an antibody to the surface of a cancer cell rarely induces cell death by itself.  Enhancing the potency of antibodies through the linkage of drug payloads provides a means to selectively kill cancer cells while limiting damage to normal tissue.

For the Exclusive License Grants, with respect to the First Exclusive Antigen, and the Option Exercise Fee  with respect to the Second Exclusive Antigen, and commencing as of the date Licensor has received the ADC Access Fee or Option Exercise Fee, as the case may be, from Licensee, Licensor shall automatically be deemed to have granted to Licensee an exclusive, even as to Licensor, license under the Licensor Technology, with the right to sublicense to discover, develop, have developed, make, have made, import, use, offer for sale, and sell Licensed Products that bind specifically to the Exclusive Antigen within the Field in the Territory.

For the Grant of Option, Licensor hereby grants Licensee an option to obtain the Exclusive License of this Agreement to the Second Exclusive Antigen during the Option Period.

For the Replacement Right; Dropped Antigen,  Licensee shall have the right to designate the first exclusive antigen as a Dropped Antigen for purposes of this Agreement by providing Licensor with written notice of same.  Licensee shall have the right to designate one (1) additional Designated Antigen as a replacement for the Dropped Antigen in accordance with  the procedure.

The patent applications include Pentapeptide Compounds and uses related thereto; Drug Conjugates and their uses for Treating Cancer, an Autoimmune Disease or an Infectious Disease; and, Monomethylvaline Compound Capable of Conjugation to Ligands.

ADC technology can be widely employed to increase the therapeutic potential of monoclonal antibodies through stable attachment to cell-killing drug payloads.

The proprietary ADC technology for use with Licensee's proprietary antibodies for the treatment of cancer.