Anti-CD26 antibodies and methods of use thereof
First Claim
Patent Images
1. A polypeptide, comprising:
- (a) one or more heavy chain CDRs selected from the group consisting of (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;
(b) one or more light chain CDRs selected from the group consisting of (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;
or one or more heavy chain CDRs as indicated in (a) and one or more light chain CDRs as indicated in (b);
wherein the polypeptide does not comprise both a heavy chain variable region of the sequence QVKLQESGPGLVQPSQTLSITCTVSGFSLTTYGVHWVRQSPGKGLEWLGVIWGGGRTD YDAAFISRLSISKDNSKSQVFFKMNSLQANDTAIYYCVRNRHDWFDYWGQGTTVTVSS (SEQ ID NO;
90) and a light chain variable region of the sequence DIQMTQSPSSLSASLGDRVTITCSASQGIRNSLNWYQQKPDGAVKLLIYYSSNLHSGVPS RFSGSGSGTDFSLTISNLEPEDIATYYCQQSIKLPFTFGSGTKLEIK (SEQ ID NO;
91).
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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.
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Citations
65 Claims
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1. A polypeptide, comprising:
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(a) one or more heavy chain CDRs selected from the group consisting of (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;
(b) one or more light chain CDRs selected from the group consisting of (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;
orone or more heavy chain CDRs as indicated in (a) and one or more light chain CDRs as indicated in (b);
wherein the polypeptide does not comprise both a heavy chain variable region of the sequence QVKLQESGPGLVQPSQTLSITCTVSGFSLTTYGVHWVRQSPGKGLEWLGVIWGGGRTD YDAAFISRLSISKDNSKSQVFFKMNSLQANDTAIYYCVRNRHDWFDYWGQGTTVTVSS (SEQ ID NO;
90) and a light chain variable region of the sequence DIQMTQSPSSLSASLGDRVTITCSASQGIRNSLNWYQQKPDGAVKLLIYYSSNLHSGVPS RFSGSGSGTDFSLTISNLEPEDIATYYCQQSIKLPFTFGSGTKLEIK (SEQ ID NO;
91). - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 62, 64)
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18. A polypeptide comprising:
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(a) an amino acid sequence consisting of EVQLVX1SGX2X3X4X5QPGX6X7LRLX8CX9ASGX10X11ILX12TYGVHWVRQAPGKG LEWX13GVIWGX14GRTDYDX15X16FMSRVTISX17DX18SKX19TX20YLQX20NSLRAEDTAV YYCX22RX23RHDWFDYWGQGTTVTVSS (SEQ ID NO;
29), 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, X9 is T or K, X10 is F or Y, X11 is S or T, X12 is T, N, or S, 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 X11X2X3TQSPSSLSX4X5X6GX7RX8TIX9CX10ASQX11IRNX12LNWYQQKPGQAPRLL IYYSSNLX13X14GVPX15RFSGSGSGTDFTLTISRLX16X17EDX18AX19YYCQQSX20KLPX21TF GSGTKVEIK (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, X7 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). - View Dependent Claims (53, 54, 55, 56, 57, 58, 59, 60, 61, 63)
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19. A polypeptide, comprising:
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(a) an amino acid sequence having at least about 80% identity to an amino acid sequence selected from the group consisting of SEQ ID NOS;
15-21;
(b) an amino acid sequence having at least about 80% identity to 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);
wherein the polypeptide does not comprise both a heavy chain variable region of the sequence QVKLQESGPGLVQPSQTLSITCTVSGFSLTTYGVHWVRQSPGKGLEWLGVIWGGGRTD YDAAFISRLSISKDNSKSQVFFKMNSLQANDTAIYYCVRNRHDWFDYWGQGTTVTVSS (SEQ ID NO;
90) and a light chain variable region of the sequence DIQMTQSPSSLSASLGDRVTITCSASQGIRNSLNWYQQKPDGAVKLLIYYSSNLHSGVPS RFSGSGSGTDFSLTISNLEPEDIATYYCQQSIKLPFTFGSGTKLEIK (SEQ ID NO;
91). - View Dependent Claims (20, 21, 22)
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23. A polypeptide comprising:
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(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);
wherein the polypeptide does not comprise both a heavy chain variable region of the sequence QVKLQESGPGLVQPSQTLSITCTVSGFSLTTYGVHWVRQSPGKGLEWLGVIWGGGRTD YDAAFISRLSISKDNSKSQVFFKMNSLQANDTAIYYCVRNRHDWFDYWGQGTTVTVSS (SEQ ID NO;
90) and a light chain variable region of the sequence DIQMTQSPSSLSASLGDRVTITCSASQGIRNSLNWYQQKPDGAVKLLIYYSSNLHSGVPS RFSGSGSGTDFSLTISNLEPEDIATYYCQQSIKLPFTFGSGTKLEIK (SEQ ID NO;
91).
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24. An antibody 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 QVKLQESGPGLVQPSQTLSITCTVSGFSLTTYGVHWVRQSPGKGLEWLGVIWGGGRTD YDAAFISRLSISKDNSKSQVFFKMNSLQANDTAIYYCVRNRHDWFDYWGQGTTVTVSS (SEQ ID NO;
90) and a light chain variable region of the sequence DIQMTQSPSSLSASLGDRVTITCSASQGIRNSLNWYQQKPDGAVKLLIYYSSNLHSGVPS RFSGSGSGTDFSLTISNLEPEDIATYYCQQSIKLPFTFGSGTKLEIK (SEQ ID NO;
91).
- 45;
- 39. A polynucleotide comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOS:
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65. An antibody encoded by the plasmid deposited with the ATCC in E. coli as accession number ______.
Specification