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US 9,708,405 B2Granted
Anti-CXCR4 antibodies and antibody-drug conjugates
AssigneePfizer Inc.
InventorsShu-Hui Liu, Flavia Mercer Pernasetti, Wei-Hsien Ho
Life of this patent
Estimating the term…
Abstract
The present invention provides antibodies and related molecules that bind to chemokine receptor 4 (CXCR4). The invention further provides antibody-drug conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and anti-CXCR4 antibody-drug conjugates for the treatment of a disorder associated with CXCR4 function or expression (e.g., cancer), such as colon, RCC, esophageal, gastric, head and neck, lung, ovarian, pancreatic cancer or hematological cancers.
Claims45
An isolated antibody, or an antigen binding fragment thereof, that binds to chemokine receptor 4 (CXCR4) and comprises:
- a) a heavy chain variable (VH) region comprising (i) a VH CDR1 selected from the group consisting of SEQ ID NOs:107, 113 and 114;
- (ii) a VH CDR2 selected from the group consisting of SEQ ID NOs:
- 162 and 128;
- and (iii) a VH CDR3 set forth as SEQ ID NO:
- 112;
- and
- b) a light chain variable region (VL) region comprising (i) a VL CDR1 set forth as SEQ ID NO:
- 144;
- (ii) a VL CDR2 set forth as SEQ ID NO:
- 145;
- and (iii) a VL CDR3 set forth as SEQ ID NO:
- 139.
9 more elements
An isolated antibody, or an antigen binding fragment thereof, that binds to chemokine receptor 4 (CXCR4) and comprises:
- a) a light chain variable (VL) region comprising (i) a VL CDR1 comprising the sequence X1SX2X3SLFNSX4X5RKNYLX6 wherein X1 is R or K;
- X2 is S or A;
- X3 is W, N or Q;
- X4 is H or R;
- X5 is T or F;
- and X6 is A, L, N, or M (SEQ ID NO:
- 151);
- (ii) a VL CDR2 comprising the sequence WASARX1S wherein X1 is G or E (SEQ ID NO:
- 152);
- and (iii) a VL CDR3 comprising the sequence KQSFX1LRT wherein X1 is N or R (SEQ ID NO:
- 153);
- and
- b) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising the sequence set forth as SEQ ID NOs:
- 107, 108, 109, 113, or 114;
- (ii) a VH CDR2 comprising the sequence set forth as SEQ ID NO:
- 157;
- and (iii) a VH CDR3 comprising the sequence set forth as SEQ ID NO:
- 112.
15 more elements
An isolated antibody, or an antigen binding fragment thereof, that binds to chemokine receptor 4 (CXCR4) and comprises:
- a) a heavy chain variable (VH) region sequence comprising:
- EVQLVESGGGLVQPGGSLRLSCAASGFTFSDYYMSWVRQAPGKGLEWVX1FIRHKX2NX3X4TX5E YSTX6X7X8GRFTISRDX9SKNX10LYLQMNSLX11X12EDTAVYYCAX13DLPGFAYWGQGTLVTVS S (SEQ ID NO:
- 106), wherein X1 is G or S;
- X2 is V or A;
- X3 is G, F, K, V, T, L, or I;
- X4 is E or Y;
- X5 is T or R;
- X6 is W or S;
- X7 is D or V;
- X8 is K, T, or R;
- X9 is D or N;
- X10 is T or S;
- X11 is R or K;
- X12 is A or T;
- and X13 is K or R;
- b) a light chain variable region (VL) region comprising (i) a VL CDR1 set forth as SEQ ID NO:
- 144;
- (ii) a VL CDR2 set forth as SEQ ID NO:
- 145;
- and (iii) a VL CDR3 set forth as SEQ ID NO:
- 139.
18 more elements
The isolated antibody or antigen binding fragment thereof that binds to chemokine receptor 4 (CXCR4) selected from the group consisting of:
- a) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107, 113 or 114;
- a VH CDR2 of SEQ ID NO:162 or 128;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:144;
- a VL CDR2 of SEQ ID NO:145;
- and a VL CDR3 of SEQ ID NO:139;
- b) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:115, 116, 117, 121 or 122;
- a VH CDR2 of SEQ ID NO:118 or 119;
- and a VH CDR3 of SEQ ID NO:120;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:135;
- a VL CDR2 of SEQ ID NO:136;
- and a VL CDR3 of SEQ ID NO:137;
- c) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107, 108, 109, 113 or 114;
- a VH CDR2 of SEQ ID NO:110 or 111;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:131;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:133;
- d) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107, 108, 109, 113 or 114;
- a VH CDR2 of SEQ ID NO:154 or 123;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:138;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:139;
- and
- e) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107, 108, 109, 113 or 114;
- a VH CDR2 of SEQ ID NO:15;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:151;
- a VL CDR2 of SEQ ID NO:152;
- and a VL CDR3 of SEQ ID NO:153.
28 more elements
The isolated antibody or antigen binding fragment thereof wherein the antibody comprises a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:162;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:144;
- a VL CDR2 of SEQ ID NO:145;
- and a VL CDR3 of SEQ ID NO:139.
2 more elements
An isolated antibody or antigen binding fragment thereof that binds to chemokine receptor 4 (CXCR4) selected from the group consisting of:
- a) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:158;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:138;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:139;
- b) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:158;
- and a VH CDR3 of SEQ ID NO:112;
- and alight chain variable (VL) region having a VL CDR1 of SEQ ID NO:138;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:140;
- c) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:158;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:150;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:140;
- d) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:158;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:141;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:140;
- e) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:158;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:144;
- a VL CDR2 of SEQ ID NO:145;
- and a VL CDR3 of SEQ ID NO:140;
- f) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:158;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:147;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:140;
- g) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:159;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:138;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:140;
- h) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:160;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:138;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:140;
- i) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:161;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:138;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:140;
- j) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:162;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:138;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:140;
- k) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:163;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:138;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:140;
- l) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:164;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:138;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:140;
- m) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:165;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:138;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:140;
- n) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:166;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:138;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:140;
- o) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:167;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:138;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:140;
- p) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:168;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:138;
- a VL CDR2 of SEQ ID NO:132;
- and a VL CDR3 of SEQ ID NO:140;
- q) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:163;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:144;
- a VL CDR2 of SEQ ID NO:145;
- and a VL CDR3 of SEQ ID NO:140;
- r) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:158;
- and a VH CDR3 of SEQ ID NO:112;
- and a VL region having a VL CDR1 of SEQ ID NO:144;
- a VL CDR2 of SEQ ID NO:145;
- and a VL CDR3 of SEQ ID NO:139;
- s) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:162;
- and a VH CDR3 of SEQ ID NO:112 and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:144;
- a VL CDR2 of SEQ ID NO:145;
- and a VL CDR3 of SEQ ID NO:139;
- t) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:163;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:144;
- a VL CDR2 of SEQ ID NO:145;
- and a VL CDR3 of SEQ ID NO:139;
- and
- u) a heavy chain variable (VH) region having a VH CDR1 of SEQ ID NO:107;
- a VH CDR2 of SEQ ID NO:162;
- and a VH CDR3 of SEQ ID NO:112;
- and a light chain variable (VL) region having a VL CDR1 of SEQ ID NO:144;
- a VL CDR2 of SEQ ID NO:145;
- and a VL CDR3 of SEQ ID NO:140.
123 more elements
Dependencies are inferred from the claim text.