Anti-ox40 antibodies and methods of use
AssigneeGenentech, Inc.
InventorsChangchun DU, Jeong Kim, Jing Zhu, Jack Bevers, III, Kevin Walsh, Patricia De Almeida, James Andya, Ye Shen
Life of this patent
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Abstract
The invention provides anti-OX40 antibodies and methods of using the same.
Claims161
An anti-human OX40 agonist antibody, wherein the antibody depletes cells that express human OX40 in vitro and binds human OX40 with an affinity of less than or equal to about 1 nM.
An anti-human OX40 agonist antibody, wherein the antibody comprises (a) a VH domain comprising i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 2, 8 or 9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 3, 10, 11, 12, 13 or 14, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:
- 4, 15, or 19;
- and (b) a VL domain comprising (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 7, 22, 23, 24, 25, 26, 27, or 28.
An agonist anti-human OX40 antibody, wherein the antibody comprises a VH sequence of SEQ ID NO:182 and a VL sequence of SEQ ID NO:
- 181.
66-70. (canceled)
A method for treating or delaying progression of cancer in an individual comprising administering to the individual an effective amount of an anti-angiogenesis agent and an OX40 binding agonist.
(canceled)
(canceled)
82-90. (canceled)
93-103. (canceled)
114-132. (canceled)
166-169. (canceled)
A kit comprising a medicament comprising an anti-angiogenesis agent and an optional pharmaceutically acceptable carrier, and a package insert comprising instructions for administration of the medicament in combination with a composition comprising an OX40 binding agonist and an optional pharmaceutically acceptable carrier for treating or delaying progression of cancer in an individual.
A kit comprising a first medicament comprising an anti-angiogenesis agent and an optional pharmaceutically acceptable carrier, and a second medicament comprising an OX40 binding agonist and an optional pharmaceutically acceptable carrier.
(canceled)
A kit comprising a medicament comprising an OX40 binding agonist and an optional pharmaceutically acceptable carrier, and a package insert comprising instructions for administration of the medicament in combination with a composition comprising an anti-angiogenesis agent and an optional pharmaceutically acceptable carrier for treating or delaying progression of cancer in an individual.
A method of detecting the presence of OX40 in a biological sample, comprising:
- (a) contacting the biological sample with an anti-OX40 antibody under conditions permissive for binding of the anti-OX40 antibody to OX40, wherein the antibody comprises:
- a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 2, 8 or 9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 3, 10, 11, 12, 13 or 14, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:
- 4, 15, or 19;
- and a VL domain comprising (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 7, 22, 23, 24, 25, 26, 27, or 28;
- and
- (b) detecting whether a complex is formed between the anti-OX40 antibody and the OX40.
A method of identifying a patient who is likely to respond to treatment with anti-human OX40 agonist antibody, comprising:
- (a) determining presence or absence or amount of cells expressing FcR in a sample of cancer from the patient;
- (b) identifying the patient as likely to respond if the sample comprises cells expressing FcR;
- (c) treating the patient with the anti-human OX40 agonist antibody, wherein the antibody comprises:
- a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 2, 8 or 9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 3, 10, 11, 12, 13 or 14, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:
- 4, 15, or 19;
- and a VL domain comprising (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 7, 22, 23, 24, 25, 26, 27, or 28.
A method of identifying a patient who is likely to respond to treatment with anti-human OX40 agonist antibody, comprising:
- (a) determining presence or absence or amount of human effector cells in a sample of cancer from the patient;
- (b) identifying the patient as likely to respond if the sample comprises effector cells;
- and
- (c) treating the patient with the anti-human OX40 agonist antibody, wherein the antibody comprises:
- a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 2, 8 or 9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 3, 10, 11, 12, 13 or 14, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:
- 4, 15, or 19;
- and a VL domain comprising (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 7, 22, 23, 24, 25, 26, 27, or 28.
A method of providing a cancer diagnosis for a patient, comprising:
- (a) measuring FcR expressing cells in a sample from the patient;
- (b) diagnosing the patient as having cancer comprising an FcR biomarker when the sample has FcR expression;
- and
- (c) selecting a therapy comprising an anti-human OX40 agonist antibody for the patient, wherein the antibody comprises:
- a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 2, 8 or 9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 3, 10, 11, 12, 13 or 14, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:
- 4, 15, or 19;
- and a VL domain comprising (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 7, 22, 23, 24, 25, 26, 27, or 28.
A method of providing a cancer diagnosis for a patient, comprising:
- (a) measuring human effector cells in a sample from the patient;
- (b) diagnosing the patient as having cancer comprising human effector cells when the sample has human effector cells;
- and
- (c) selecting a therapy comprising an anti-human OX40 agonist antibody for the patient, wherein the antibody comprises:
- a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 2, 8 or 9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 3, 10, 11, 12, 13 or 14, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:
- 4, 15, or 19;
- and a VL domain comprising (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 7, 22, 23, 24, 25, 26, 27, or 28.
A method of recommending a treatment to a cancer patient, comprising:
- (a) measuring FcR expressing cells in a sample from the patient;
- (b) recommending treatment with an anti-human OX40 agonist antibody when the sample has FcR expressing cells, wherein the antibody comprises:
- a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 2, 8 or 9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 3, 10, 11, 12, 13 or 14, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:
- 4, 15, or 19;
- and a VL domain comprising (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 7, 22, 23, 24, 25, 26, 27, or 28.
A method of recommending a treatment to a cancer patient, comprising:
- (a) measuring human effector cells in a sample from the patient;
- and
- (b) recommending treatment with an anti-human OX40 agonist antibody when the sample has human effector cells, wherein the antibody comprises:
- a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 2, 8 or 9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 3, 10, 11, 12, 13 or 14, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NO:
- 4, 15, or 19;
- and a VL domain comprising (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 7, 22, 23, 24, 25, 26, 27, or 28.
Dependencies are inferred from the claim text.