Anti-CD26 antibodies and methods of use thereof

• US 7,462,698 B2
• Filed: 07/24/2006
• Issued: 12/09/2008
• Est. Priority Date: 07/22/2005
• Status: Active Grant

• Current Assignee: Y's AC Co., Ltd.
• Original Assignee: Y's Therapeutics Co., Ltd.
• Inventors: Zhong, Pingyu, Hsieh, Mark, Aoyagi, Teikichi, Morimoto, Chikao, Luo, Peter Peizhi, Li, Yan, Wang, Kevin Caili
• Primary Examiner(s): Blanchard; David J.
• Assistant Examiner(s): GUSSOW, ANNE
• Application Number:
  US11/492,498
• Publication Number:
  US 20070105771A1
• Time in Patent Office: 869 Days
• Field of Search: None
• US Class Current: 530/387.3
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• 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 2317/567 Framework region [FR]
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: G01N 2333/70596 Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 33/574 : for cancer
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides novel anti-CD26 antibodies and other, related polypeptides, as well as novel polynucleotides encoding the antibodies and polypeptides. The invention also provides methods of making the antibodies and polypeptides. Compositions and cells comprising the antibodies or polypeptides are further provided. Methods of using the antibodies and/or polypeptides, such as to inhibit cell proliferation and in the treatment of conditions associated with CD26, are also provided.

Claims

1. An isolated antibody, comprising:

(a) heavy chain CDRs comprising (i) a heavy chain CDR1 comprising the sequence GX₁X₂LX₃TYGVH (SEQ ID NO;

31), wherein X₁ is F or Y, X₂ is S or T, and X₃ is T, N, or S, (ii) a heavy chain CDR2 comprising the sequence VIWGX₁GRTDYDX₂X₃FMS (SEQ ID NO;

32), wherein X₁ is G or D, X₂ is A or S, and X₃ is A or S, and (iii) a heavy chain CDR3 comprising the sequence X₁RHDWFDY (SEQ ID NO;

33), wherein X₁ is N or S; and

(b) light chain CDRs comprising (i) a light chain CDR1 comprising the sequence X₁ASQX₂IRNX₃LN (SEQ ID NO;

34), wherein X₁ is S or R, X₂ is G or D, and X₃ is S or N, (ii) a light chain CDR2 comprising the sequence YSSNLX₁X₂ (SEQ ID NO;

35), wherein X₁ is H or Q and X₂ is S or T, and (iii) a light chain CDR3 comprising the sequence QQSX₁KLPX₂T (SEQ ID NO;

36), wherein X₁ is I or N and X₂ is F or L; and

wherein the antibody binds CD26.

2. The antibody of claim 1, wherein the heavy chain CDR1 comprises a sequence selected from the group consisting of GFSLTTYGVH (SEQ ID NO:

55), GFSLSTYGVH (SEQ ID NO;

     56), and GYSLTTYGVH (SEQ ID NO;

     57).

3. The antibody of claim 1, wherein the heavy chain CDR2 comprises a sequence selected from the group consisting of VIWGDGRTDYDAAFMS (SEQ ID NO:

58) and VIWGDGRTDYDSSFMS (SEQ ID NO;

     59).

4. The antibody of claim 1, wherein the heavy chain CDR3 comprises the sequence NRHDWFDY (SEQ ID NO:

60).

5. The antibody of claim 1, which comprises

(a) heavy chain CDRs comprising

(i) a CDR1 comprising the sequence GFSLTTYGVH (SEQ ID NO:

55),

(ii) a CDR2 comprising the sequence VIWGDGRTDYDAAFMS (SEQ ID NO;

     58), and

(iii) a CDR3 comprising the sequence NRHDWFDY (SEQ ID NO;

     60);

(b) heavy chain CDRs comprising

(i) a CDR1 comprising the sequence GFSLSTYGVH (SEQ ID NO;

     56),

(ii) a CDR2 comprising the sequence VIWGDGRTDYDAAFMS (SEQ ID NO;

     58), and

(iii) a CDR3 comprising the sequence NRHDWFDY (SEQ ID NO;

     60);

or

(c) heavy chain CDRs comprising

(i) a CDR1 comprising the sequence GYSLTTYGVH (SEQ ID NO;

     57), (ii) a CDR2 comprising the sequence VIWGDGRTDYDSSFMS (SEQ ID NO;

     59), and (iii) a CDR3 comprising the sequence NRHDWFDY (SEQ ID NO;

     60).

6. The antibody of claim 5, which further comprises

(a) light chain CDRs comprising

(i) a CDR1 comprising the sequence RASQDIRNNLN (SEQ ID NO:

61),

(ii) a CDR2 comprising the sequence YSSNLHS (SEQ ID NO;

     64), and

(iii) a CDR3 comprising the sequence QQSIKLPLT (SEQ ID NO;

     67);

(b) light chain CDRs comprising

(i) a CDR1 comprising the sequence RASQGIRNNLN (SEQ ID NO;

     62),

(ii) a CDR2 comprising the sequence YSSNLQS (SEQ ID NO;

     65), and

(iii) a CDR3 comprising the sequence QQSIKLPFT (SEQ ID NO;

     68);

or

(c) light chain CDRs comprising

(i) a CDR1 comprising the sequence SASQDIRNSLN (SEQ ID NO;

     63),

(ii) a CDR2 comprising the sequence YSSNLHT (SEQ ID NO;

     66), and

(iii) a CDR3 comprising the sequence QQSNKLPLT (SEQ ID NO;

     69).

7. The antibody of claim 1, wherein the light chain CDR1comprises a sequence selected from the group consisting of RASQDIRNNLN (SEQ ID NO:

61), RASQGIRNNLN (SEQ ID NO;

     62), and SASQDIRNSLN (SEQ ID NO;

     63).

8. The antibody of claim 1, wherein the light chain CDR2 comprises a sequence selected from the group consisting of YSSNLHS (SEQ ID NO:

64), YSSN LOS (SEQ ID NO;

     65) and YSSNLHT (SEQ ID NO;

     66).

9. The antibody of claim 1, wherein the light chain CDR3 comprises a sequence selected from the group consisting of QQSIKLPLT (SEQ ID NO:

67), QQSIKLPFT (SEQ ID NO;

     68), and QQSNKLPLT (SEQ ID NO;

     69).

10. The antibody of claim 1, which comprises

(a) light chain CDRs comprising

(i) a CDR1 comprising the sequence RASQDIRNNLN (SEQ ID NO:

61),

(ii) a CDR2 comprising the sequence YSSNLHS (SEQ ID NO;

     64), and

(iii) a CDR3 comprising the sequence QQSIKLPLT (SEQ ID NO;

     67);

(b) light chain CDRs comprising

(i) a CDR1 comprising the sequence RASQGIRNNLN (SEQ ID NO;

     62),

(ii) a CDR2 comprising the sequence YSSNLQS (SEQ ID NO;

     65), and

(iii) a CDR3 comprising the sequence QQSIKLPFT (SEQ ID NO;

     68);

or

(c) light chain CDRs comprising

(i) a CDR1 comprising the sequence SASQDIRNSLN (SEQ ID NO;

     63),

(ii) a CDR2 comprising the sequence YSSNLHT (SEQ ID NO;

     66), and

(iii) a CDR3 comprising the sequence QQSNKLPLT (SEQ ID NO;

     69).

11. The antibody of claim 1, wherein the antibody further comprises

(a) one or more heavy chain framework regions selected from the group consisting of (i) a heavy chain FR1 comprising the sequence EVQLVX₁SGX₂X₃X₄X₅QPGX₆X₇LRLX₈CX₉AS (SEQ ID NO:

37), wherein X₁ is E or Q X₂ is A or G, X₃ is G or E, X₄ is L or V, X₅ is V, K, or E, X₆ is G or E, X₇ is T or S X₈ is T or S, and X₉ is T or K;

(ii) a heavy chain FR2 comprising the sequence WVRQAPGKGLEWX₁G (SEQ ID NO;

38), wherein X₁ is V or M, (iii) a heavy chain FR3 comprising the sequence RVTISX₁DX₂SKX₃TX₄YLQX₅NSLRAEDTAVYYCX₆R (SEQ ID NO;

39), wherein X₁ is K or R, X₂ is N or T, X₃ is S or N, X₄ is V or A, X₅ is M or L, and X₆ is V, M, or T, and (iv) a heavy chain FR4 comprising the sequence WGQGTTVTVSS (SEQ ID NO;

40);

(b) one or more light chain framework regions selected from the group consisting of (i) a light chain FR1 comprising the sequence X₁IX₂X₃TQSPSSLSX₄X₅X₆GX₇RX₈TIX₉C (SEQ ID NO;

41), wherein X₁ is D or E, X₂ is L or E, X₃ is M or L, X₄ is A or V, X₅ is S or T, X₆ is L, P, or A, X₇ is D or E, X₈ is V or A, and X₉ is T or S, (ii) a light chain FR2 comprising the sequence WYQQKPGQAPRLLIY (SEQ ID NO;

     42), (iii) a light chain FR3 comprising the sequence GVPX1RFSGSGSGTDFTLTISRLX₂X₃EDX₄AX₅YYC (SEQ ID NO;

     43), wherein X₁ is S, D, or A, X₂ is E or Q, X₃ is P or A, X₄ is F or V, and X₅ is T, A, or I, and

(iv) a light chain FR4 comprising the sequence FGSGTKVEIK (SEQ ID NO;

44);

or

(c) one or more heavy chain framework regions as indicated in (a) and one or more light chain framework regions as indicated in (b).

15. An isolated antibody of claim 1 further comprising:

(a) heavy chain framework regions comprising (i) a heavy chain FR1 comprising the sequence EVQLVX₁SGX₂X₃X₄X₅QPGX₆X₇LRLX₈CX₉AS (SEQ ID NO;

37), wherein X₁ is E or Q, X₂ is A or G, X₃ is G or E, X₄ is L or V, X₅ is V, K, or E, X₆ is G or E, X₇ is T or S, X₈ is T or S, and X₉ is T or K;

(ii) a heavy chain FR2 comprising the sequence WVRQAPGKGLEWX₁G (SEQ ID NO;

38), wherein X₁ is V or M, (iii) a heavy chain FR3 comprising the sequence RVTISX₁DX₂SKX₃TX₄YLQX₅NSLRAEDTAVYYCX₆R (SEQ ID NO;

39), wherein X₁ is K or R, X₂ is N or T, X₃ is S or N, X₄ is V or A, X₅ is M or L, and X₆ is V, M, or T, and (iv) a heavy chain FR4 comprising the sequence WGQGTTVTVSS (SEQ ID NO;

40); and

(b) light chain framework regions comprising (i) a light chain FR1 comprising the sequence X₁IX₂X₃TQSPSSLSX₄X₅X₆GX₇RX₈TIX₉C (SEQ ID NO;

41), wherein X₁ is D or E, X₂ is L or E, X₃ is M or L, X₄ is A or V, X₅ is S or T, X₆ is L, P, or A, X₇ is D or E, X₈ is V or A, and X₉ is T or S, (ii) a light chain FR2 comprising the sequence WYQQKPGQAPRLLIY (SEQ ID NO;

     42), (iii) a light chain FR3 comprising the sequence GVPX₁RFSGSGSGTDFTLTISRLX₂X₃EDX₄AX₅YYC (SEQ ID NO;

     43), wherein X₁ is S, D, or A, X₂ is E or Q, X₃ is P or A, X₄ is F or V, and X₅ is T, A, or I, and (iv) a light chain FR4 comprising the sequence FGSGTKVEIK (SEQ ID NO;

44).

17. The antibody of claim 1, which is a monoclonal antibody.

18. The antibody of claim 1, which is a humanized antibody.

19. The antibody of claim 1, which is an antigen binding antibody fragment.

20. The antibody of claim 19, wherein the antibody fragment is selected from the group consisting of Fab, Fab'"'"', Fab'"'"'-SH, Fv, scFv and F(ab'"'"')2.

21. The antibody of claim 1 which is not a murine monoclonal antibody.

22. The antibody of claim 1, wherein the CD26 is human CD26.

23. The antibody of claim 22, which binds to human CD26 with a KD of about 6 nM or less.

24. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable excipient.

26. The antibody of claim 6, which comprises

(a) heavy chain CDRs comprising:

(i) a CDR1 comprising the sequence GFSLTTYGVH (SEQ ID NO;

55);

(ii) a CDR2 comprising the sequence VIWGDGRTDYDAAFMS (SEQ ID NO;

58); and

(iii) a CDR3 comprising the sequence NRHDWFDY (SEQ ID NO;

60); and

(b) light chain CDRs comprising;

(i) a CDR1 comprising the sequence RASQGIRNNLN (SEQ ID NO;

62);

(ii) a CDR2 comprising the sequence YSSNLQS (SEQ ID NO;

65); and

(iii) a CDR3 comprising the sequence QQSIKLPFT (SEQ ID NO;

68).

29. The antibody of claim 15,which is not a murine monoclonal antibody.

30. The antibody of claim 15, which is not a murine monoclonal antibody.

32. A pharmaceutical composition comprising the antibody of claim 26 and a pharmaceutically acceptable excipient.

12. An isolated antibody comprising:

(a) an amino acid sequence consisting of EVQLVX₁ SGX₂X₃X₄X₅QPGX₆X₇LRLX₈CX₉ASGX₁₀X₁₁ LX₁₂TYGVHWVRQAPGKGLE WX₁₃GVIWGX₁₄GRTDYDX₁₅X₁₆FMSRVTISX₁₇DX₁₈SKX₁₉TX₂₀YLQX₂₁NSLRAEDTAVY YCX₂₂RX₂₃RHDWFDYWGQGTTVTVSS (SEQ ID NO;

29), wherein X₁ is E or S, X₂ is A or G, X₃ is G or E, X₄ is L or V, X₅ is V, K, or E, X₆ is G or E, X₇ is T or S, X₈ is T or S, X₉ is T or K, X10 is F or Y, X11 is S or T, X12 is T, N, or 5, X13 is V or M, X14 is G or D, X15 is A or S, X₁₆ is A or S, X₁₇ is K or R, X₁₈ is N or T, X₁₉ is S or N, X₂₀ is V or A, X₂₁ is M or L, X₂₂ is V, M, or T, and X₂₃ is N or S;

(b) an amino acid sequence consisting of X₁ IX₂X₃TQSPSSLSX₄X₅X₆GX₇RX₈TIX₉CX_{10 1}ASQX₁₁ IRNX₁₂LNWYQQKPGQAPRLLIYYS SNLX₁₃X₁₄GVPX₁₅RFSGSGS GTDFTLTISRLX₁₆X₁₇EDX₁₈AX₁₉YYCQQSX₂₀KLPX₂₁TFGSGTKVEIK (SEQ ID NO;

30), wherein X₁ is D or E, X₂ is L or E, X₃ is M or L, X₄ is A or V, X₅ is S or T, X₆ is L, P, or A, X_{b 7} is D or E, X₈ is V or A, X₉ is T or S, X₁₀ is S or R, X₁₁ is G or D, X₁₂ is S or N, X₁₃ is H or Q, X₁₄ is S or T, X₁₅ is S, D, or A, X₁₆ is E or Q, X₁₇ is P or A, X₁₈ is F or V, X₁₉ is T, A, or I, X₂₀ is I or N and X₂₁ is F or L;

or

(c) both the amino acid sequence indicated in (a) and the amino acid sequence indicated in (b);

wherein the antibody binds CD26.

25. A pharmaceutical composition comprising the antibody of claim 12, 13, or 15 and a pharmaceutically acceptable excipient.

28. The antibody of claim 12, which is not a murine monoclonal antibody.

13. An isolated antibody comprising:

(a) an amino acid sequence selected from the group consisting of SEQ ID NOS;

15-21;

(b) an amino acid sequence selected from the group consisting of SEQ ID NOS;

22-28;

or

(c) an amino acid sequence as indicated in (a) and an amino acid sequence as indicated in (b) and wherein the antibody binds CD26.

14. The antibody of claim 13, which comprises

(a) a heavy chain variable region comprising amino acid sequence SEQ ID NO:

26 and a light chain variable region comprising amino acid sequence SEQ ID NO;

15;

(b) a heavy chain variable region comprising amino acid sequence SEQ ID NO;

22 and a light chain variable region comprising amino acid sequence SEQ ID NO;

18;

(c) a heavy chain variable region comprising amino acid sequence SEQ ID NO;

28 and a light chain variable region comprising amino acid sequence SEQ ID NO;

19;

or

(d) a heavy chain variable region comprising amino acid sequence SEQ ID NO;

23 and a light chain variable region comprising amino acid sequence SEQ ID NO;

19.

16. An isolated antibody that binds CD26 and that binds to one or more peptides selected from the group consisting of YSLRWISDHEYLY (SEQ ID NO:

45;

peptide

     6), LEYNYVKQWRHSY (SEQ ID NO;

46;

peptide

     35), TWSPVGHKLAYVW (SEQ ID NO;

47;

peptide

     55), LWWSPNGTFLAYA (SEQ ID NO;

48;

peptide

     84), RISLQWLRRIQNY (SEQ ID NO;

49;

peptide

     132), YVKQWRHSYTASY (SEQ ID NO;

50;

peptide

     37), EEEVFSAYSALWW (SEQ ID NO;

51;

peptide

     79), DYSISPDGQFILL (SEQ ID NO;

52;

peptide

     29), SISPDGQFILLEY (SEQ ID NO;

53;

peptide

     30), and IYVKIEPNLPSYR (SEQ ID NO;

54;

peptide

     63), wherein the antibody does not comprise both a heavy chain variable region of the sequence QVKLQESGPGLVQPSQTLSITCTVSGFSLTTYGVHWVRQSPGKGLEWLGVIWGGGRT DYDAAFISRLSISKDNSKS QVFFKMNSLQANDTAIYYCVRNRHDWFDYWGQGTTVTVSS (SEQ ID NO;

90) and a light chain variable region of the sequence DIQMTQSPSSLSASLGDRVTITCSASQGIRNSLNWYQQKPDGAVKLLIYYSSNLHSGVP SRF SGSGSGTDFSLTISNLEPEDIATYYCQQSIKLPFTFGSGTKLEIK (SEQ ID NO;

91).

31. The antibody of claim 16, which is not a murine monoclonal antibody.

33. A pharmaceutical composition comprising the antibody of claim 16 and a pharmaceutically acceptable excipient.

27. An antibody encoded by the plasmid deposited with the ATCC in E coli as accession number PTA-7695.