Targeting ABCB5 for cancer therapy

• US 7,928,202 B2
• Filed: 04/11/2008
• Issued: 04/19/2011
• Est. Priority Date: 04/12/2007
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated
• Original Assignee: Brigham and Women's Hospital Incorporated
• Inventors: Sayegh, Mohamed H., Frank, Natasha Y., Frank, Markus H.
• Primary Examiner(s): HUFF, SHEELA JITENDRA
• Application Number:
  US12/101,428
• Publication Number:
  US 20090117117A1
• Time in Patent Office: 1,103 Days
• Field of Search: None
• US Class Current: 530/387.3
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 47/6851 the antibody targeting a determinant of a tumour cell
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C12N 15/1135 against oncogenes or tumor suppressor genes
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/3513 Protein; Peptide
• CPC Class Codes: C12N 2320/32 Special delivery means, e.g. tissue-specific
• CPC Class Codes: C12Y 302/02022 rRNA N-glycosylase (3.2.2.22)
• CPC Class Codes: G01N 2333/705 Assays involving receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: G01N 33/57492 : involving compounds localized on the membrane of tumor or cancer cells

Abstract

The invention relates to methods for treating a subject by manipulating ABCB5 on a cell as well as related products. The methods include methods of treating cancer using ABCB5 binding molecules such as antibodies and fragments thereof.

Claims

1. A composition, comprising

an isolated peptide that selectively binds to ABCB5 and comprises an amino acid sequence having the following CDRs:

CDR1-H1;

SEQ ID NO;

3, CDR2-H2;

SEQ ID NO;

4, CDR3-H3;

SEQ ID NO;

5, CDR1-L1;

SEQ ID NO;

6, CDR2-L2;

SEQ ID NO;

7, and CDR3-L3;

SEQ ID NO;

8, wherein the isolated peptide is not mAb 3C2-1D12.

6. The isolated peptide of claim 1 which is a single chain Fv.

7. The isolated peptide of claim 1 which is a Fab, Fab′

, F(ab′

)₂, Fv, scFv, dsFv, Fd, VH dAb, or VL dAb isolated peptide.

8. The isolated peptide of claim 1, wherein the isolated peptide is a monoclonal antibody.

9. The isolated peptide of claim 1, wherein the isolated peptide is a bispecific antibody.

17. The composition of claim 1, wherein the isolated peptide is an isolated antibody or antibody fragment.

18. The composition of claim 17, wherein the isolated antibody is a monoclonal antibody.

19. The composition of claim 17, wherein the isolated antibody or antibody fragment is an isolated monoclonal antibody fragment selected from the group consisting of an Fab, Fab′

, F(ab′

)₂, Fv, scFv, dsFv, Fd, VH dAb, and VL dAb.

20. The composition of claim 17, wherein the isolated antibody or antibody fragment enhances chemosensitization.

21. The composition of claim 1, wherein the isolated peptide is conjugated to a detectable label.

22. The composition of claim 1, further comprising a pharmaceutically acceptable carrier.

23. The composition of claim 17, wherein the isolated antibody or antibody fragment is a humanized antibody.

24. The composition of claim 1, wherein the isolated peptide is a scFv.

2. A composition, comprising

an isolated peptide that selectively binds to ABCB5 comprising at least two antibody variable domains defined by SEQ ID NO:

1 and SEQ ID NO;

2, wherein the isolated peptide is not mAb 3C2-1D12.

3. The composition of claim 2 wherein the isolated peptide is conjugated to a therapeutic agent.

4. The composition of claim 3 wherein the therapeutic agent is selected from the group consisting of camptothecin 9-NH2, mitoxantrone, camptothecin 7-Cl, pyrazofurin, menogaril, camptothecin 20 ester, camptothecin, amsacrine, etopside, anthrapyrazole-derivitive, terniposide, camptothecin 11-formyl, camptothecin 10-OH, daunorubicin, doxydoxorubicin, doxorubicin, oxanthrazoole, camptothecin 11-HOMe, zorubicin, uracil mustard, piperazinedione, hepsulfam, melphalan, bisantrene, triethylenemelamine, spiromustine, Yoshi-864, chlorambucil, piperazine mustard, hydroyurea, porfiromycin, mechlorethamine, fluorodopan, mitomycin, cytarabine (araC), dianhydrogalactitol, gemcitabine, thiotepa, N,N-dibenzyl-daunomycin, teroxirone, and aphidicolin-glycinate.

10. The isolated peptide of claim 2, wherein the isolated peptide is a synthetic antibody.

5. A kit, comprising

a container housing an isolated peptide that selectively binds to ABCB5 and comprises an amino acid sequence comprising SEQ ID NO:

1 and SEQ ID NO;

2, or an amino acid sequence having all of the following CDRs;

CDR1-H1;

SEQ ID NO;

3, CDR2-H2;

SEQ ID NO;

4, CDR3-H3;

SEQ ID NO;

5, CDR1-L1;

SEQ ID NO;

6, CDR2-L2;

SEQ ID NO;

7, and CDR3-L3;

SEQ ID NO;

8, and instructions for administering the isolated peptide to a human subject.

11. An anti-ABCB5 antibody or antigen-binding fragment thereof, having at least one human region, wherein the anti-ABCB5 antibody or antigen binding fragment competitively inhibits binding of mAb 3C2-1D12 to ABCB5.

12. The antibody of claim 11, wherein the antigen-binding fragment is selected from the group consisting of Fab, Fab′

, F(ab′

)₂, Fv, scFv, dsFv, Fd, VH dAb, and VL dAb.

13. The antibody of claim 11, wherein the antibody or antigen-binding fragment is of immunoglobulin class IgA, IgGb 1, IgG2, IgG3, IgG4 or IgM.

14. The antibody of claim 11, wherein the antibody or antigen-binding fragment comprises a human constant region and a human variable framework region.

15. The antibody of claim 11, wherein the antigen-binding fragment is a single chain antibody.

16. A chimeric antibody comprising a heavy chain and light chain variable domain which specifically binds to ABCB5 and a constant domain, wherein the variable domain and the constant domain are from different species.