# US 2016/0257752 A1 · Methods of treating cancers using pd-1 axis binding antagonists and taxanes

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- Number: US 2016/0257752 A1
- Document ID: US20160257752A1
- Status: Published application
- Kind: A1
- Application number: 15/167,125
- Filed: 2016-05-27
- Published: 2016-09-08
- Earliest claimed: 2013-12-17
- Assignees: Genentech, Inc.
- Applicants: Genentech, Inc.
- Inventors: Jeong KIM; Jeanne CHEUNG
- Web page: https://patentgrep.com/patent/US20160257752A1

## CPC

- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- C07K 16/32: against translation products of oncogenes
- A61K 31/282: Platinum compounds
- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/643: {Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]}
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C07K 16/30: from tumour cells
- C07K 16/3015: {Breast}
- C07K 16/3023: {Lung}
- C07K 16/303: {Liver or Pancreas}
- C07K 16/3038: {Kidney, bladder}
- C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/524: CH2 domain
- C07K 2317/526: CH3 domain
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention provides methods and compositions for treating cancer and for enhancing immune function in an individual having cancer. The methods comprise administering a PD-1 axis binding antagonist and a taxane.

## Claims

### Claim 1

A method for treating or delaying progression of cancer in an individual comprising administering to the individual an effective amount of a human PD-1 axis binding antagonist and a taxane.

### Claim 2 (depends on 1)

The method of claim 1, wherein the PD-1 axis binding antagonist is selected from the group consisting of a PD-1 binding antagonist, a PD-L1 binding antagonist, and a PD-L2 binding antagonist.

### Claim 3 (depends on 2)

The method of claim 2, wherein the PD-1 axis binding antagonist is a PD-1 binding antagonist.

### Claim 4 (depends on 3)

The method of claim 3, wherein the PD-1 binding antagonist inhibits the binding of PD-1 to its ligand binding partners.

### Claim 5 (depends on 4)

The method of claim 4, wherein the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L1.

### Claim 6 (depends on 4)

The method of claim 4, wherein the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L2.

### Claim 7 (depends on 4)

The method of claim 4, wherein the PD-1 binding antagonist inhibits the binding of PD-1 to both PD-L1 and PD-L2.

### Claim 8 (depends on 4, 5, 6, 7)

The method of any one of claims 4-7, wherein the PD-1 binding antagonist is an antibody.

### Claim 9 (depends on 4)

The method of claim 4, wherein the PD-1 binding antagonist is selected from the group consisting of MDX-1106 (nivolumab), MK-3475 (lambrolizumab), CT-011 (pidilizumab), and AMP-224.

### Claim 10 (depends on 2)

The method of claim 2, wherein the PD-1 axis binding antagonist is a PD-L1 binding antagonist.

### Claim 11 (depends on 10)

The method of claim 10, wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to PD-1.

### Claim 12 (depends on 10)

The method of claim 10, wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to B7-1.

### Claim 13 (depends on 10)

The method of claim 10, wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to both PD-1 and B7-1.

### Claim 14 (depends on 11, 12, 13)

The method of any one of claims 11-13, wherein the PD-L1 binding antagonist is an antibody.

### Claim 15 (depends on 14)

The method of claim 14, wherein the antibody is selected from the group consisting of: YW243.55.570, MPDL3280A, MDX-1105, and MED14736.

### Claim 16 (depends on 14)

The method of claim 14, wherein the antibody comprises a heavy chain comprising HVR-H1 sequence of SEQ ID NO:19, HVR-H2 sequence of SEQ ID NO:20, and HVR-H3 sequence of SEQ ID NO:21; and a light chain comprising HVR-L1 sequence of SEQ ID NO:22, HVR-L2 sequence of SEQ ID NO:23, and HVR-L3 sequence of SEQ ID NO:24.

### Claim 17 (depends on 14)

The method of claim 14, wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:26 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:4.

### Claim 18 (depends on 2)

The method of claim 2, wherein the PD-1 axis binding antagonist is a PD-L2 binding antagonist.

### Claim 19 (depends on 18)

The method of claim 18, wherein the PD-L2 binding antagonist is an antibody.

### Claim 20 (depends on 18)

The method of claim 18, wherein the PD-L2 binding antagonist is an immunoadhesin.

### Claim 21 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)

The method of any one of claims 1-20, wherein the cancer is lung cancer, bladder cancer, breast cancer, renal cell carcinoma, melanoma, colorectal cancer, or a heme malignancy.

### Claim 22 (depends on 21)

The method of claim 21, wherein the lung cancer is non-small cell lung cancer (NSCLC).

### Claim 23 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22)

The method of any one of claims 1-22, wherein the individual has cancer or has been diagnosed with cancer.

### Claim 24 (depends on 23)

The method of claim 23, wherein the cancer cells in the individual express PD-L1.

### Claim 25 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24)

The method of any one of claims 1-24, wherein the treatment results in a response in the individual.

### Claim 26 (depends on 25)

The method of claim 25, wherein the response is a complete response.

### Claim 27 (depends on 25, 26)

The method of claim 25 or claim 26, wherein the response is a sustained response after cessation of the treatment.

### Claim 28 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)

The method of any one of claims 1-27, wherein the taxane is administered before the PD-1 axis binding antagonist, simultaneous with the PD-1 axis binding antagonist, or after the PD-1 axis binding antagonist.

### Claim 29 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28)

The method of any one of claims 1-28, wherein the taxane is nab-paclitaxel (ABRAXANE®), paclitaxel, or docetaxel.

### Claim 30 (depends on 29)

The method of claim 29, wherein the taxane is nab-paclitaxel (ABRAXANE®).

### Claim 31 (depends on 29)

The method of claim 29, wherein the taxane is paclitaxel.

### Claim 32

A method of enhancing immune function in an individual having cancer comprising administering an effective amount of a PD-1 axis binding antagonist and a taxane.

### Claim 33 (depends on 32)

The method of claim 32, wherein CD8+ T cells in the individual have enhanced priming, activation, proliferation and/or cytolytic activity relative to prior to the administration of the PD-1 axis binding antagonist and the taxane.

### Claim 34 (depends on 32)

The method of claim 32, wherein the number of CD8+ T cells is elevated relative to prior to administration of the combination.

### Claim 35 (depends on 34)

The method of claim 34, wherein the CD8+ T cell is an antigen-specific CD8+ T cell.

### Claim 36 (depends on 32)

The method of claim 32, wherein Treg function is suppressed relative to prior to the administration of the combination.

### Claim 37 (depends on 32)

The method of claim 32, wherein T cell exhaustion is decreased relative to prior to the administration of the combination.

### Claim 38 (depends on 32, 33, 34, 35, 36, 37)

The method of any one of claims 32-37, wherein the PD-1 axis binding antagonist is selected from the group consisting of a PD-1 binding antagonist, a PD-L1 binding antagonist and a PD-L2 binding antagonist.

### Claim 39 (depends on 38)

The method of claim 38, wherein the PD-1 axis binding antagonist is a PD-1 binding antagonist.

### Claim 40 (depends on 39)

The method of claim 39, wherein the PD-1 binding antagonist inhibits the binding of PD-1 to its ligand binding partners.

### Claim 41 (depends on 40)

The method of claim 40, wherein the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L1.

### Claim 42 (depends on 40)

The method of claim 40, wherein the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L2.

### Claim 43 (depends on 40)

The method of claim 40, wherein the PD-1 binding antagonist inhibits the binding of PD-1 to both PD-L1 and PD-L2.

### Claim 44 (depends on 40, 41, 42, 43)

The method of any one of claims 40-43, wherein the PD-1 binding antagonist is an antibody.

### Claim 45 (depends on 40)

The method of claim 40, wherein the PD-1 binding antagonist is selected from the group consisting of MDX-1106 (nivolumab), MK-3475 (lambrolizumab), CT-011 (pidilizumab), and AMP-224.

### Claim 46 (depends on 38)

The method of claim 38, wherein the PD-1 axis binding antagonist is a PD-L1 binding antagonist.

### Claim 47 (depends on 46)

The method of claim 46, wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to PD-1.

### Claim 48 (depends on 46)

The method of claim 46, wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to B7-1.

### Claim 49 (depends on 46)

The method of claim 46, wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to both PD-1 and B7-1.

### Claim 50 (depends on 46, 47, 48, 49)

The method of any one of claims 46-49, wherein the PD-L1 binding antagonist is an antibody.

### Claim 51 (depends on 50)

The method of claim 50, wherein antibody is selected from the group consisting of: YW243.55.570, MPDL3280A, MDX-1105, and MED14736.

### Claim 52 (depends on 50)

The method of claim 50, wherein the antibody comprises a heavy chain comprising HVR-H1 sequence of SEQ ID NO:19, HVR-H2 sequence of SEQ ID NO:20, and HVR-H3 sequence of SEQ ID NO:21; and a light chain comprising HVR-L1 sequence of SEQ ID NO:22, HVR-L2 sequence of SEQ ID NO:23, and HVR-L3 sequence of SEQ ID NO:24.

### Claim 53 (depends on 50)

The method of claim 50, wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:26 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:4.

### Claim 54 (depends on 38)

The method of claim 38, wherein the PD-1 axis binding antagonist is a PD-L2 binding antagonist.

### Claim 55 (depends on 54)

The method of claim 54, wherein the PD-L2 binding antagonist is an antibody.

### Claim 56 (depends on 54)

The method of claim 54, wherein the PD-L2 binding antagonist is an immunoadhesin.

### Claim 57 (depends on 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56)

The method of any one of claims 32-56, wherein the cancer is lung cancer, bladder cancer, breast cancer, renal cell carcinoma, melanoma, colorectal cancer, or a heme malignancy.

### Claim 58 (depends on 57)

The method of claim 57, wherein the lung cancer is non-small cell lung cancer (NSCLC).

### Claim 59 (depends on 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58)

The method of any one of claims 32-58, wherein the cancer cells in the individual express PD-L1.

### Claim 60 (depends on 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59)

The method of any one of claims 32-59, wherein the taxane is nab-paclitaxel (ABRAXANE®), paclitaxel, or docetaxel.

### Claim 61 (depends on 60)

The method of claim 60, wherein the taxane is nab-paclitaxel (ABRAXANE®).

### Claim 62 (depends on 60)

The method of claim 60, wherein the taxane is paclitaxel.

### Claim 63 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62)

The method of any one of claims 1-62, wherein the PD-1 axis binding antagonist and/or the taxane are administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, or intranasally.

### Claim 64 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63)

The method of any one of claims 1-63, further comprising administering an effective amount of a chemotherapeutic agent.

### Claim 65 (depends on 64)

The method of claim 64, wherein the chemotherapeutic agent is a platinum-based chemotherapeutic agent.

### Claim 66 (depends on 65)

The method of claim 65, wherein the platinum-based chemotherapeutic agent is carboplatin.

### Claim 67

Use of a human PD-1 axis binding antagonist in the manufacture of a medicament for treating or delaying progression of cancer in an individual, wherein the medicament comprises the human PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier, and wherein the treatment comprises administration of the medicament in combination with a composition comprising a taxane and an optional pharmaceutically acceptable carrier.

### Claim 68

Use of a taxane in the manufacture of a medicament for treating or delaying progression of cancer in an individual, wherein the medicament comprises the taxane and an optional pharmaceutically acceptable carrier, and wherein the treatment comprises administration of the medicament in combination with a composition comprising a human PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier.

### Claim 69

A composition comprising a human PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier for use in treating or delaying progression of cancer in an individual, wherein the treatment comprises administration of said composition in combination with a second composition, wherein the second composition comprises a taxane and an optional pharmaceutically acceptable carrier.

### Claim 70

A composition comprising a taxane and an optional pharmaceutically acceptable carrier for use in treating or delaying progression of cancer in an individual, wherein the treatment comprises administration of said composition in combination with a second composition, wherein the second composition comprises a human PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier.

### Claim 71

A kit comprising a medicament comprising a PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier, and a package insert comprising instructions for administration of the medicament in combination with a composition comprising a taxane and an optional pharmaceutically acceptable carrier for treating or delaying progression of cancer in an individual.

### Claim 72

A kit comprising a first medicament comprising a PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier, and a second medicament comprising a taxane and an optional pharmaceutically acceptable carrier.

### Claim 73 (depends on 72)

The kit of claim 72, wherein the kit further comprises a package insert comprising instructions for administration of the first medicament and the second medicament for treating or delaying progression of cancer in an individual.

### Claim 74

A kit comprising a medicament comprising a taxane and an optional pharmaceutically acceptable carrier, and a package insert comprising instructions for administration of the medicament in combination with a composition comprising a PD-1 axis binding antagonist and an optional pharmaceutically acceptable carrier for treating or delaying progression of cancer in an individual.