Claims for Patent: 8,927,694
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Summary for Patent: 8,927,694
Title: | Human serum albumin linkers and conjugates thereof |
Abstract: | Disclosed is a human serum albumin (HSA) linker and HSA linker with binding, diagnostic, and therapeutic agents conjugated thereto. Also disclosed is a conjugate in which the HSA linker is covalently bonded to amino and carboxy terminal binding moieties that are first and second single-chain Fv molecules (scFvs). Exemplified conjugates are useful, e.g., in reducing tumor cell proliferation, e.g., for therapeutic therapeutic applications. Also disclosed are methods and kits for the diagnostic and therapeutic application of an HSA linker conjugate. |
Inventor(s): | McDonagh; Charlotte (Winchester, MA), Feldhaus; Michael (Grantham, NH), Huhalov; Alexandra (Cambridge, MA) |
Assignee: | Merrimack Pharmaceuticals, Inc. (Cambridge, MA) |
Application Number: | 13/130,007 |
Patent Claims: | 1. A human serum albumin (HSA) linker conjugate that is: a) HSA linker conjugate B2B3-1 having or comprising an amino acid sequence that is SEQ ID NO:16; or b) HSA linker
conjugate B2B3-2 having or comprising an amino acid sequence that is SEQ ID NO:17; or c) HSA linker conjugate B2B3-3 having or comprising an amino acid sequence that is SEQ ID NO:18; or d) HSA linker conjugate B2B3-4 having or comprising an amino acid
sequence that is SEQ ID NO:19; or e) HSA linker conjugate B2B3-5 having or comprising an amino acid sequence that is SEQ ID NO:20; or f) HSA linker conjugate B2B3-6 having or comprising an amino acid sequence that is SEQ ID NO:21; or g) HSA linker
conjugate B2B3-7 having or comprising an amino acid sequence that is SEQ ID NO:22; or h) HSA linker conjugate B2B3-8 having or comprising an amino acid sequence that is SEQ ID NO:23; or i) HSA linker conjugate B2B3-10 having or comprising an amino acid
sequence that is SEQ ID NO:25.
2. The HSA linker conjugate of claim 1 admixed with a pharmaceutically acceptable carrier, excipient, or diluent. 3. A composition comprising the HSA linker conjugate of claim 1 in combination with one or more therapeutic agents selected from the group consisting of cyclophosphamide, camptothecin, homocamptothecin, colchicine, combretastatin, rhizoxin, dolistatin, ansamitocin p3, maytansinoid, auristatin, caleachimicin, methotrexate, 5-fluorouracil (5-FU), doxorubicin, paclitaxel, docetaxel, cisplatin, carboplatin, tamoxifen, raloxifene, letrozole, epirubicin, bevacizumab, pertuzumab, trastuzumab, and derivatives thereof. 4. The composition of claim 3 wherein the therapeutic agent is trastuzumab. 5. The composition of claim 3 wherein the therapeutic agent is trastuzumab and the HSA linker conjugate is HSA linker conjugate B2B3-1 having or comprising an amino acid sequence that is SEQ ID NO:16. 6. The composition of claim 5 wherein, when tested in a nude mouse human xenograft model using human breast tumor cells at a first dosage of the therapeutic agent and a second dosage of the HSA linker conjugate, the combination provides greater efficacy than is provided by the first dosage of the therapeutic agent alone or the second dosage of the HSA linker conjugate alone in the same model. 7. The composition of claim 6 in a dosage form that can be administered to a subject to provide at least 3 mg/kg of B2B3-1 and at least 0.1 mg/kg trastuzumab. 8. The composition of claim 3, wherein the therapeutic agent is paclitaxel or docetaxel. 9. The composition of claim 3 wherein the therapeutic agent is a letrozole. 10. The HSA linker conjugate of claim 1, wherein said HSA linker conjugate binds ErbB3 with a K.sub.d of about 16 nM and ErbB2 with a K.sub.d of about 0.3 nM. 11. A method of treating a subject, said subject being in need of treatment for a tumor, said treating comprising administering to the subject an effective amount of the HSA linker conjugate of claim 1. 12. A method of treating a subject, said subject being in need of treatment for a tumor, said treating comprising administering to the subject an effective amount of the composition of claim 3. 13. An HSA linker conjugate comprising: i) a human serum albumin (HSA) linker comprising an amino acid sequence set forth in any one of SEQ ID NOs:6-15; and ii) first and second binding moieties selected from the group consisting of antibodies, single-chain Fv molecules, bispecific single chain Fv ((scFv').sub.2) molecules, domain antibodies, diabodies, triabodies, hormones, Fab fragments, F(ab').sub.2 molecules, tandem scFv (taFv) fragments, receptors, ligands, aptamers, and biologically-active fragments thereof, wherein said first binding moiety is bonded to the amino terminus of said HSA linker and said second binding moiety is bonded to the carboxy terminus of said HSA linker. 14. A HSA linker conjugate comprising the amino acid sequence of SEQ ID NO:16. 15. The HSA linker conjugate of claim 14 consisting of the amino acid sequence of SEQ ID NO:16. 16. A composition comprising the HSA linker conjugate of claim 14 in combination with one or more therapeutic agents selected from the group consisting of cyclophosphamide, camptothecin, homocamptothecin, colchicine, combretastatin, rhizoxin, dolistatin, ansamitocin p3, maytansinoid, auristatin, caleachimicin, methotrexate, 5-fluorouracil (5-FU), doxorubicin, paclitaxel, docetaxel, cisplatin, carboplatin, tamoxifen, raloxifene, letrozole, epirubicin, bevacizumab, pertuzumab, trastuzumab, and derivatives thereof. 17. The composition of claim 16, wherein the HSA linker conjugate consists of the amino acid sequence of SEQ ID NO: 16. 18. The composition of claim 16, wherein the therapeutic agent is trastuzumab. 19. The composition of claim 18, wherein the HSA linker conjugate consists of the amino acid sequence of SEQ ID NO: 16. 20. The method of claim 11, wherein said HSA linker conjugate consists of the amino acid sequence of SEQ ID NO: 16. 21. The method of claim 12, wherein said HSA linker conjugate consists of the amino acid sequence of SEQ ID NO: 16. |
Details for Patent 8,927,694
Applicant | Tradename | Biologic Ingredient | Dosage Form | BLA | Approval Date | Patent No. | Expiredate |
---|---|---|---|---|---|---|---|
Genentech, Inc. | HERCEPTIN | trastuzumab | For Injection | 103792 | 09/25/1998 | ⤷ Try a Trial | 2028-11-18 |
Genentech, Inc. | HERCEPTIN | trastuzumab | For Injection | 103792 | 02/10/2017 | ⤷ Try a Trial | 2028-11-18 |
Genentech, Inc. | AVASTIN | bevacizumab | Injection | 125085 | 02/26/2004 | ⤷ Try a Trial | 2028-11-18 |
Genentech, Inc. | PERJETA | pertuzumab | Injection | 125409 | 06/08/2012 | ⤷ Try a Trial | 2028-11-18 |
Genentech, Inc. | HERCEPTIN HYLECTA | trastuzumab and hyaluronidase-oysk | Injection | 761106 | 02/28/2019 | ⤷ Try a Trial | 2028-11-18 |
>Applicant | >Tradename | >Biologic Ingredient | >Dosage Form | >BLA | >Approval Date | >Patent No. | >Expiredate |
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