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US 2017/0247454 A1Published application
Anti-pd1 antibodies and methods of use
AssigneeHoffmann-La Roche Inc.
InventorsJoerg Benz, Laura Codarri Deak, Stefan Dengl, Sebastian Fenn, Jens Fischer, Guy Georges, Christian Klein, Viktor Levitski, Valeria Lifke, Oliver Ploettner, Stefan Seeber, Barbara Weiser, Ildiko Wuensche, Adrian Zwick
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Abstract
The present invention relates to anti-PD1 antibodies and methods of using the same.
Claims30
An isolated antibody that binds to human PD1, wherein the antibody binds to the (core) sugar chain at Asn58 of glycosylated human PD1 of SEQ ID NO:
- 70 which is glycosylated at Asn58.
An isolated antibody that binds to human PD1, wherein the antibody comprises
- (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:71;
- (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:72;
- (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:73;
- (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:74;
- (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:75;
- (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:76, and (g) FR-H3 comprising the amino acid sequence of SEQ ID NO:
- 77 (of RDN) at positions of 71, 72 and 73 according to Kabat numbering
4 more elements
An isolated antibody that binds to human PD1, wherein the antibody comprises
- A) (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:1;
- (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:2;
- (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:3;
- (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:4;
- (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:5;
- and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:6;
- or
- B) (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:9;
- (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:10;
- (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:11;
- (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:12;
- (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:13;
- and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:14;
- or
- C) (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:17;
- (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:18;
- (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:19;
- (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:20;
- (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:21;
- and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:22;
- or
- D) (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:25;
- (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:26;
- (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:27;
- (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:28;
- (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:29;
- and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:30;
- or
- E) (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:33;
- (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:34;
- (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:35;
- (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:36;
- (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:37;
- and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:38;
- or
- F) (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:41;
- (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:42;
- (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:43;
- (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:44;
- (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:45;
- and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:46;
- or
- G) (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:49;
- (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:50;
- (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:51;
- (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:52;
- (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:53;
- and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:54.
45 more elements
An isolated antibody that binds to human PD1, wherein the antibody comprises
- A) (a) a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:1, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:2, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:3;
- and (b) a VL domain comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:4;
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:5 and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:6;
- or
- B) (a) a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:10, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:11;
- and (b) a VL domain comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:12;
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:13 and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:14;
- or
- C) (a) a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:17, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:18, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:19;
- and (b) a VL domain comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:20;
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:21 and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:22;
- or.
- D) (a) a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:25, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:26, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:27;
- and (b) a VL domain comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:28;
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:29 and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:30;
- or
- E) (a) a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:33, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:34, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:35;
- and (b) a VL domain comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:36;
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:37 and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:38;
- or
- F) (a) a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:41, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:42, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:43;
- and (b) a VL domain comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:44;
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:45 and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:46;
- or
- G) (a) a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:49, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:50, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:51;
- and (b) a VL domain comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:52;
- (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:53 and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:54.
24 more elements
An isolated antibody that binds to human PD1, wherein the antibody
- A)
- i) comprises a VH sequence of SEQ ID NO:7 and a VL sequence of SEQ ID NO:8;
- ii) or humanized variant of the VH and VL of the antibody under i);
- or B)
- i) comprises a VH sequence of SEQ ID NO:57 and a VL sequence of SEQ ID NO:58.
- ii) comprises a VH sequence of SEQ ID NO:57 and a VL sequence of SEQ ID NO:59.
- iii) comprises a VH sequence of SEQ ID NO:57 and a VL sequence of SEQ ID NO:60.
- iv) comprises a VH sequence of SEQ ID NO:57 and a VL sequence of SEQ ID NO:61.
- or C)
- i) comprises a VH sequence of SEQ ID NO:15 and a VL sequence of SEQ ID NO:16;
- ii) or humanized variant of the VH and VL of the antibody under i);
- or D)
- i) comprises a VH sequence of SEQ ID NO:23 and a VL sequence of SEQ ID NO:24;
- ii) or humanized variant of the VH and VL of the antibody under i);
- or E)
- i) comprises a VH sequence of SEQ ID NO:31 and a VL sequence of SEQ ID NO:32;
- ii) or humanized variant of the VH and VL of the antibody under i);
- or F)
- i) comprises a VH sequence of SEQ ID NO:39 and a VL sequence of SEQ ID NO:40;
- ii) or humanized variant of the VH and VL of the antibody under i);
- or G)
- i) comprises a VH sequence of SEQ ID NO:47 and a VL sequence of SEQ ID NO:48;
- ii) or humanized variant of the VH and VL of the antibody under i);
- or H)
- i) comprises a VH sequence of SEQ ID NO:55 and a VL sequence of SEQ ID NO:56;
- ii) or humanized variant of the VH and VL of the antibody under i).
23 more elements
An isolated antibody that binds to human PD1, wherein the antibody
- i) comprises a VH sequence of SEQ ID NO:7 and a VL sequence of SEQ ID NO:8;
- ii) or humanized variant of the VH and VL of the antibody under i);
An isolated antibody that binds to human PD1, wherein the antibody comprises a VH sequence of SEQ ID NO:57 and a VL sequence of SEQ ID NO:58.
An isolated antibody that binds to human PD1, wherein the antibody comprises a VH sequence of SEQ ID NO:57 and a VL sequence of SEQ ID NO:59.
An isolated antibody that binds to human PD1, wherein the antibody comprises a VH sequence of SEQ ID NO:57 and a VL sequence of SEQ ID NO:60.
An isolated antibody that binds to human PD1, wherein the antibody comprises a VH sequence of SEQ ID NO:57 and a VL sequence of SEQ ID NO:61.
An isolated antibody that binds to PD1, wherein the antibody enhances the tumor necrosis factor alpha (TNF alpha) secretion by allogenic stimulated T cells by 200% or more at an antibody concentration of 10 μg/ml in a Mixed lymphocyte reaction (MLR) assay.
An isolated antibody that binds to PD1, wherein the antibody enhances the interferon-gamma (IFN-gamma) secretion by allogenic stimulated T cells by 85% or more at an antibody concentration of 10 μg/ml in a Mixed lymphocyte reaction (MLR) assay.
An isolated antibody that binds to human PD-1, wherein the antibody:
- i) competes for binding to PD-1 with an anti-PD1 antibody comprising the VH with the amino acid sequence of SEQ ID NO:7 and VL with the amino acid sequence of SEQ ID NO:8, and/or
- ii) binds to a human and cynomolguoes PD-1;
- and
- iii) enhances the interferon-gamma (IFN-gamma) secretion by allogenic stimulated T cells by 85% or more at an antibody concentration of 10 μg/ml;
- and
- iv) enhances the tumor necrosis factor alpha (TNF alpha) secretion by allogenic stimulated T cells by 200% or more at an antibody concentration of 10 μg/ml.
3 more elements
29-32. (canceled)
Dependencies are inferred from the claim text.