US2010292312A1PendingUtilityA1

Anti-dll4 antibodies and methods using same

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Assignee: GENENTECH INCPriority: Jun 6, 2006Filed: Aug 2, 2010Published: Nov 18, 2010
Est. expiryJun 6, 2026(expired)· nominal 20-yr term from priority
Inventors:Minhong YanYan Wu
A61P 35/04A61P 35/02A61P 35/00A61P 27/02C07K 2317/24C07K 2317/92A61K 45/06C07K 2317/565C07K 2317/33A61K 2039/507C07K 2317/74C07K 16/22C07K 2317/76A61K 2039/505A61P 11/00A61P 1/04A61P 15/00C07K 2317/73A61K 39/395C12N 15/11
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Claims

Abstract

The invention provides anti-DLL4 antibodies, and compositions comprising and methods of using these antibodies.

Claims

exact text as granted — not AI-modified
1 . A polynucleotide encoding an isolated anti-DLL4 antibody comprising:
 (a) at least one, two, three, four or five hypervariable region (HVR) sequences selected from the group consisting of:   (i) HVR-L1 comprising sequence A1-A11, wherein A1-A11 is RASQDVSTAVA (SEQ ID NO: 10)   (ii) HVR-L2 comprising sequence B1-B7, wherein B1-B7 is SASFLYS (SEQ ID NO:11)   (iii) HVR-L3 comprising sequence C1-C9, wherein C1-C9 is QQSYTGTVT (SEQ ID NO:18)   (iv) HVR-H1 comprising sequence D1-D10, wherein D1-D10 is GFTFTDNWIS (SEQ ID NO:1);   (v) HVR-H2 comprising sequence E1-E18, wherein E1-E18 is GYISPNSGFTYYADSVKG (SEQ ID NO:8) and   (vi) HVR-H3 comprising sequence F1-F15, wherein F1-F15 is VYYCARDNFGGYFDY (SEQ ID NO:9); and   (b) at least one variant HVR, wherein the variant HVR sequence comprises modification of at least one residue of the sequence depicted in SEQ ID NOs:1-18.   
     
     
         2 . A polynucleotide encoding an isolated anti-DLL4 antibody comprising:
 (a) at least one, two, three, four or five hypervariable region (HVR) sequences selected from the group consisting of:   (i) HVR-L1 comprising sequence A1-A11, wherein A1-A11 is RASQDVSTAVA (SEQ ID NO: 10)   (ii) HVR-L2 comprising sequence B1-B7, wherein B1-B7 is SASFLYS (SEQ ID NO:11)   (iii) HVR-L3 comprising sequence C 1 -C 9 , wherein C1-C9 is QQSYNGPST (SEQ ID NO:15)   (iv) HVR-H1 comprising sequence D1-D10, wherein D1-D10 is GFTFTDNWIS (SEQ ID NO:1)   (v) HVR-H2 comprising sequence E1-E 18, wherein E1-E 18 is GVINPNSGATEYADSVKG (SEQ ID NO:5) and   (vi) HVR-H3 comprising sequence F1-F15, wherein F1-F15 is VYYCARDNFGGYFDY (SEQ ID NO:9); and   (b) at least one variant HVR, wherein the variant HVR sequence comprises modification of at least one residue of the sequence depicted in SEQ ID NOs:1-18.   
     
     
         3 . The polynucleotide of  claim 1  or  2 , wherein a HVR-L3 variant comprises 1-6 (1, 2, 3, 4, 5, or 6) substitutions in any combination of the following positions: 91 (S or W), 92 (Y or F), 93 (T, N or S), 94 (T or G), 95 (P, Q, A or T), and/or 96 (P, S, A, or V). 
     
     
         4 . The polynucleotide of  claim 1  or  2 , wherein a HVR-H2 variant comprises 1-4 (1, 2, 3, or 4) substitutions in any combination of the following positions: 50 (V, L or Y), 52 (N or S), 52a (P or S), or 53 (N, Q, T, or I). 
     
     
         5 . A polynucleotide encoding an isolated anti-DLL4 antibody comprising one, two, three, four, five or six HVRs, wherein each HVR comprises, consists or consists essentially of a sequence selected from the group consisting of SEQ ID NOs: 1-18, and wherein SEQ ID NO:10 corresponds to an HVR-L1, SEQ ID NO:11 corresponds to an HVR-L2, SEQ ID NO:12, 13, 14, 15, 16, 17, or 18 correspond to an HVR-L3, SEQ ID NO:1 or 2 correspond to an HVR-H1, SEQ ID NO:3, 4, 5, 6, 7 or 8 correspond to an HVR-H2, and SEQ ID NO:9 corresponds to an HVR-H3. 
     
     
         6 . The polynucleotide of  claim 5 , wherein the antibody comprises HVR-L1, HVR-L2, HVR-L3, HVR-H1, HVR-H2, and HVR-H3, wherein each, in order, comprises SEQ ID NO:10, 11, 14, 2, 3, and 9. 
     
     
         7 . The polynucleotide of  claim 5 , wherein the antibody comprises HVR-L1, HVR-L2, HVR-L3, HVR-H1, HVR-H2, and HVR-H3, wherein each, in order, comprises SEQ ID NO:10, 11, 15, 1, 5, and 9. 
     
     
         8 . The polynucleotide of  claim 5 , wherein the antibody comprises HVR-L1, HVR-L2, HVR-L3, HVR-H1, HVR-H2, and HVR-H3, wherein each, in order, comprises SEQ ID NO:10, 11, 16, 1, 6, and 9. 
     
     
         9 . The polynucleotide of  claim 5 , wherein the antibody comprises HVR-L1, HVR-L2, HVR-L3, HVR-H1, HVR-H2, and HVR-H3, wherein each, in order, comprises SEQ ID NO:10, 11, 17, 1, 7, and 9. 
     
     
         10 . The polynucleotide of  claim 5 , wherein the antibody comprises HVR-L1, HVR-L2, HVR-L3, HVR-H1, HVR-H2, and HVR-H3, wherein each, in order, comprises SEQ ID NO:10, 11, 18, 1, 8, and 9. 
     
     
         11 . The polynucleotide of any of  claims 1 - 10 , wherein at least a portion of the framework sequence is a human consensus framework sequence. 
     
     
         12 . The polynucleotide of  claim 1  or  2 , wherein the modification is substitution, insertion or deletion. 
     
     
         13 . The polynucleotide of any of  claims 1 - 12 , wherein the antibody comprises human κ subgroup consensus framework sequence. 
     
     
         14 . The polynucleotide of any of  claims 1 - 12 , wherein the antibody comprises heavy chain human subgroup III consensus framework sequence. 
     
     
         15 . The polynucleotide of  claim 14 , wherein the antibody comprises a substitution at one or more of position 71, 73 or 78. 
     
     
         16 . The polynucleotide of  claim 15 , wherein the substitution is one or more of R71A, N73T, or N78A. 
     
     
         17 . (canceled) 
     
     
         18 . A vector comprising the polynucleotide of any of  claims 1 - 16 . 
     
     
         19 . The vector of  claim 18 , wherein the vector is an expression vector. 
     
     
         20 . A host cell comprising a vector of  claim 18  or  19 . 
     
     
         21 . The host cell of  claim 20 , wherein the host cell is prokaryotic. 
     
     
         22 . The host cell of  claim 20 , wherein the host cell is eukaryotic. 
     
     
         23 . The host cell of  claim 20 , wherein the host cell is mammalian. 
     
     
         24 . A method for making an anti-DLL4 antibody, said method comprising (a) expressing a vector of  claim 19  in a suitable host cell, and (b) recovering the antibody. 
     
     
         25 . A method for making an anti-DLL4 immunoconjugate, said method comprising (a) expressing a vector of  claim 19  in a suitable host cell, and (b) recovering the antibody. 
     
     
         26 . The method of  claim 24  or  25 , wherein the host cell is prokaryotic. 
     
     
         27 . The method of  claim 24  or  25 , wherein the host cell is eukaryotic. 
     
     
         28 - 31 . (canceled) 
     
     
         32 . A composition comprising a polynucleotide of any of  claims 1 - 16  and  18 - 19 . 
     
     
         33 . The composition of  claim 32 , wherein the composition further comprises a carrier. 
     
     
         34 - 43 . (canceled)

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