Get our Free Patent Expiration Newsletter

Serving leading biopharmaceutical companies globally:

Medtronic
Mallinckrodt
Colorcon
Merck
Express Scripts
Baxter

Last Updated: October 18, 2019

DrugPatentWatch Database Preview

Claims for Patent: 8,927,694

See Plans and Pricing

« Back to Dashboard

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.

Summary for Patent:   Start Trial

PCT Information
PCT FiledOctober 14, 2009PCT Application Number:PCT/US2009/060721
PCT Publication Date:May 27, 2010PCT Publication Number:WO2010/059315

Details for Patent 8,927,694

Applicant Tradename Biologic Ingredient Dosage Form BLA Number Approval Date Patent No. Assignee Estimated Patent Expiration Status Orphan Source
Genentech HERCEPTIN trastuzumab VIAL; INTRAVENOUS 103792 001 1998-09-25   Start Trial Merrimack Pharmaceuticals, Inc. (Cambridge, MA) 2028-11-18 RX Orphan search
Genentech AVASTIN bevacizumab VIAL; INTRAVENOUS 125085 001 2004-02-26   Start Trial Merrimack Pharmaceuticals, Inc. (Cambridge, MA) 2028-11-18 RX search
Genentech AVASTIN bevacizumab VIAL; INTRAVENOUS 125085 002 2004-02-26   Start Trial Merrimack Pharmaceuticals, Inc. (Cambridge, MA) 2028-11-18 RX search
Genentech PERJETA pertuzumab VIAL; SINGLE-USE 125409 001 2012-06-08   Start Trial Merrimack Pharmaceuticals, Inc. (Cambridge, MA) 2028-11-18 RX search
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Number >Approval Date >Patent No. >Assignee >Estimated Patent Expiration >Status >Orphan >Source

International Patent Family for US Patent 8,927,694

Make Better Decisions: Try a trial or see plans & pricing

Serving leading biopharmaceutical companies globally:

Dow
Boehringer Ingelheim
AstraZeneca
Medtronic
Mallinckrodt
McKinsey

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.