# US 2019/0161547 A1 · Methods for regulating endogenous production of checkpoint molecule antagonists

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- Number: US 2019/0161547 A1
- Document ID: US20190161547A1
- Status: Published application
- Kind: A1
- Application number: 15/826,267
- Filed: 2017-11-29
- Published: 2019-05-30
- Earliest claimed: 2017-11-29
- Assignees: Wyvern Pharmaceutical Inc.
- Applicants: Wyvern Pharmaceutical Inc.
- Inventors: Bradley G. THOMPSON
- Web page: https://patentgrep.com/patent/US20190161547A1

## CPC

- C07K 16/2818: {against CD28 or CD152}
- A61K 31/685: one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 38/1709: {from mammals}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present disclosure relates to one or more agents, therapies, treatments, and methods of use of the agents and/or therapies and/or treatments for decreasing production and/or functionality of one or more immune checkpoint molecules. Embodiments of the present disclosure can be used as a therapy or a treatment for a subject that has an infection or infections, or cancer or cancers

## Claims

### Claim 1

A method of making an agent/target cell complex, the method comprising a step of administering a therapeutically effective amount of an agent to a subject, wherein the agent/target cell complex increases the subject's endogenous production and/or a functionality of an antagonist of a checkpoint molecule.

### Claim 2 (depends on 1)

The method of claim 1, wherein the antagonist is an inhibitory checkpoint antagonist.

### Claim 3 (depends on 1)

The method of claim 1, wherein the antagonist is a checkpoint protein antagonist and/or a phosphatidylserine antagonist.

### Claim 4 (depends on 2)

The method of claim 2, wherein the antagonist is a regulatory molecule.

### Claim 5 (depends on 1)

The method of claim 1, wherein the checkpoint molecule is at least one of cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), programmed death ligand 2 (PD-L2), indoleamine 2,3-dioxygenase 1 (IDO1) and phosphatidylserine.

### Claim 6 (depends on 1)

The method of claim 1, wherein the agent is at least one of a gene vector used for gene therapy, one or more selected nucleotides, a sequence of nucleotides, one or more nucleosides, a sequence of nucleosides, a DNA complex, one or more amino acids, a sequence of amino acids, a live microorganism, an attenuated microorganism, a dead microorganism, a recombinant virus and a non-recombinant virus.

### Claim 7 (depends on 1)

The method of claim 1, wherein the agent/target cell complex comprises a target cell that is at least one of an adrenal gland cell; a B cell; a bile duct cell; a chondrocyte; a cochlear cell; a corneal cell; an endocardium cell; an endometrial cell; an endothelial cell; an epithelial cell; an eosinophil; a fibroblast; a hair follicle cell; a hepatocyte; a lymph node cell; a macrophage; a mucosal cell; a myocyte; a neuron; a glomeruli cell; an optic nerve cell; an osteoblast; an ovarian tissue cell; a pancreatic islet beta cell; a pericardium cell; a platelet; a red blood cell (RBC); a retinal cell; a scleral cell; a Schwann cell; a T cell; a testicular tissue cell; a thyroid gland cell; and a uveal cell.

### Claim 8 (depends on 1)

The method of claim 1, wherein the agent/target cell complex comprises a target cell that is at least one of a lung cancer cell, a small cell lung cancer cell, a non-small cell lung cancer cell, a large cell lung cancer cell, a renal cancer cell, a colorectal cancer cell, a penile cancer cell, a bile duct cancer cell, a melanoma cancer cell, a non-melanoma skin cancer cell, a pancreatic cancer cell, a breast cancer cell, a cervical cancer cell, an endometrial cancer cell, a fallopian tube cancer cell, a throat cancer cell, an oral cancer cell, a prostate cancer cell, a brain cancer cell, a glioma cell, an astrocytoma cancer cell, a neuroblastoma cancer cell, an adrenal cancer cell, an anal cancer cell, a thyroid cancer cell, a bone cancer cell, an osteosarcoma sarcoma cell, a soft tissue sarcoma cell, a uterine cancer cell, a spinal cancer cell, a testicular cancer cell, a head and neck cancer cell, an ovarian cancer cell, a vaginal cancer cell, a vulvar cancer cell, a stomach cancer cell, a squamous cell cancer cell, a sinus cancer cell, a throat cancer cell, an ocular cancer cell, a liver cancer cell, an intestinal cancer cell, a lymph node cancer cell, a gall bladder cancer cell, and an esophageal cancer cell.

### Claim 9 (depends on 1)

The method of claim 1, further comprising a step of administering a second agent that decreases a production and/or a functionality of a second checkpoint molecule.

### Claim 10 (depends on 9)

The method of claim 9, wherein the second agent second increases a production and/or a functionality of a regulatory molecule that decreases the production and/or the functionality of the second checkpoint molecule.

### Claim 11 (depends on 9)

The method of claim 9, further comprising a step of administering a third agent that decreases a production and/or a functionality of a third checkpoint molecule.

### Claim 12 (depends on 11)

The method of claim 11, wherein the third agent increases the production and/or functionality of a regulatory molecule that decreases the production and/or the functionality of the third checkpoint molecule.

### Claim 13 (depends on 11)

The method of claim 11, further comprising a step of administering a fourth agent that decreases a production and/or a functionality of a fourth checkpoint molecule.

### Claim 14 (depends on 13)

The method of claim 13, wherein the fourth agent increases the production and/or functionality of a regulatory molecule that decreases the production and/or the functionality of the fourth checkpoint molecule.

### Claim 15 (depends on 13)

The method of claim 13, further comprising a step of administering a fifth agent that decreases a production and/or a functionality of a fifth checkpoint molecule.

### Claim 16 (depends on 15)

The method of claim 15, wherein the fifth agent increases the production and/or functionality of a regulatory molecule that decreases the production and/or the functionality of the fifth checkpoint molecule.

### Claim 17 (depends on 15)

The method of claim 15, further comprising a step of administering a sixth agent that decreases a production and/or a functionality of a sixth checkpoint molecule.

### Claim 18 (depends on 17)

The method of claim 17, wherein the sixth agent increases the production and/or functionality of a regulatory molecule that decreases the production and/or the functionality of the sixth checkpoint molecule.

### Claim 19

A pharmaceutical composition comprising:
a. an agent that decreases a production and/or a functionality of one or more checkpoint molecules and/or the agent increases a production and/or a functionality of one or more regulatory molecules that decrease a production and/or a functionality of the one or more checkpoint molecules;
b. a pharmaceutically acceptable carrier; and/or
c. an excipient.

### Claim 20 (depends on 19)

The pharmaceutical composition according to claim 19, wherein the one or more checkpoint molecules is an inhibitory checkpoint molecule.

### Claim 21 (depends on 19)

The pharmaceutical composition according to claim 19, wherein the one or more checkpoint molecules is at least one of cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), programmed death ligand 2 (PD-L2), indoleamine 2,3-dioxygenase 1 (IDO1) and phosphatidylserine.

### Claim 22 (depends on 19)

The pharmaceutical composition of claim 19, further comprising a second agent that decreases a production and/or a functionality of a second checkpoint molecule.

### Claim 23 (depends on 22)

The pharmaceutical composition of claim 22, wherein the second agent increases a production and/or a functionality of a second regulatory molecule that decreases the production and/or the functionality of the second checkpoint molecule.

### Claim 24 (depends on 22)

The pharmaceutical composition of claim 22, further comprising a third agent that decreases a production and/or a functionality of a third checkpoint molecule.

### Claim 25 (depends on 24)

The pharmaceutical composition of claim 24, wherein the third agent increases a production and/or a functionality of a regulatory molecule that decreases the production and/or the functionality of the third checkpoint molecule.

### Claim 26 (depends on 24)

The pharmaceutical composition of claim 24, further comprising a fourth agent that decreases a production and/or a functionality of a fourth checkpoint molecule.

### Claim 27 (depends on 26)

The pharmaceutical composition of claim 26, wherein the fourth agent increases a production and/or a functionality of a regulatory molecule that decreases the production and/or the functionality of the fourth checkpoint molecule.

### Claim 28 (depends on 26)

The pharmaceutical composition of claim 26, further comprising a fifth agent that decreases a production and/or a functionality of a fifth checkpoint molecule.

### Claim 29 (depends on 28)

The pharmaceutical composition of claim 28, wherein the fifth agent increases a production and/or a functionality of a regulatory molecule that decreases the production and/or the functionality of the fifth checkpoint molecule.

### Claim 30 (depends on 28)

The pharmaceutical composition of claim 28, further comprising a sixth agent that decreases a production and/or a functionality of a sixth checkpoint molecule.

### Claim 31 (depends on 30)

The pharmaceutical composition of claim 30, wherein the sixth agent increases a production and/or a functionality of a regulatory molecule that decreases the production and/or the functionality of the sixth checkpoint molecule.

### Claim 32 (depends on 19)

The pharmaceutical composition according to claim 19, wherein the pharmaceutical composition is in a solid form or a liquid form.

### Claim 33

A method of treating an infection, the method comprising a step of administering to a subject a therapeutically effective amount of an agent that decreases a production and/or a functionality of three or more checkpoint molecules.

### Claim 34 (depends on 33)

The method according to claim 33, wherein the infection is at least one of a chronic viral infection, a chronic bacterial infection, a chronic mycoplasma infection, a chronic plasmodium infection, a chronic amoeba infection, a chronic fungus infection, and a chronic parasite infection.

### Claim 35 (depends on 33)

The method according to claim 33, wherein the agent decreases the production and/or the functionality of four or more checkpoint molecules.

### Claim 36 (depends on 33)

The method according to claim 33, wherein the agent decreases the production and/or the functionality of five or more checkpoint molecules.

### Claim 37 (depends on 33)

The method according to claim 33, wherein the agent decreases the production and/or the functionality of six or more checkpoint molecules.

### Claim 38 (depends on 33)

The method according to claim 33, wherein the three or more checkpoint molecules are inhibitory checkpoint molecules.

### Claim 39 (depends on 33)

The method according to claim 33, wherein at least one of the three or more checkpoint molecules are a checkpoint protein.

### Claim 40 (depends on 33)

The method according to claim 33, wherein at least one of the three or more checkpoint molecules are a checkpoint lipid.

### Claim 41

A method of treating a cancer, the method comprising a step of administering to a subject a therapeutically effective amount of an agent that decreases a production and/or a functionality of three or more checkpoint molecules.

### Claim 42 (depends on 41)

The method according to claim 41, wherein the cancer is at least one of lung cancer, small cell lung cancer, non-small cell lung cancer, large cell lung cancer, renal cancer, colorectal cancer, bile duct cancer, penile cancer, melanoma cancer, non-melanoma skin cancer, cervical cancer, endometrial cancer, pancreatic cancer, breast cancer, oral cancer, brain cancer, glioma, astrocytoma, neuroblastoma, prostate cancer, adrenal cancer, anal cancer, thyroid cancer, bone cancer, osteosarcoma, soft tissue sarcoma, uterine cancer, fallopian tube cancer, spinal cancer, testicular cancer, head and neck cancer, ovarian cancer, vaginal cancer, vulvar cancer, stomach cancer, squamous cell cancer, sinus cancer, throat cancer, oral cancer, ocular cancer, liver cancer, intestinal cancer, gall bladder cancer, cancers of the lymph node, and esophageal cancer.

### Claim 43 (depends on 41)

The method of treating cancer of claim 41, wherein the agent decreases the production and/or functionality of four or more checkpoint molecules.

### Claim 44 (depends on 41)

The method of treating cancer of claim 41, wherein the agent decreases the production and/or functionality of five or more checkpoint molecules.

### Claim 45 (depends on 41)

The method of treating cancer of claim 41, wherein the agent decreases the production and/or functionality of six or more checkpoint molecules.

### Claim 46 (depends on 41)

The method according to claim 41, wherein the step of administering occurs by at least one of an intravenous route, an intramuscular route, an intraperitoneal route, an intrathecal route, an intravesical route, a topical route, an intranasal route, a transmucosal route, and a pulmonary route.

### Claim 47 (depends on 41)

The method according to claim 41, wherein each of the three or more checkpoint molecules is cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), programmed death ligand 2 (PD-L2), indoleamine 2,3-dioxygenase 1 (IDO1) and phosphatidylserine and combinations thereof.

### Claim 48 (depends on 41)

The method according to claim 41, wherein the agent increases a production and/or a functionality of a regulatory molecule that decreases the production of or the functionality of at least one of the three or more checkpoint molecules.

### Claim 49 (depends on 48)

The method according to claim 48, wherein the regulatory molecule is a sequence of DNA and/or a sequence of RNA that decreases production of at least one of the three or more checkpoint molecules.

### Claim 50 (depends on 41)

The method according to claim 41, wherein the agent is a vector containing a gene or genes for decreasing the levels of at least one of CTLA-4, PD-1, PD-L1, PD-L2, IDO1 and PS.

### Claim 51 (depends on 41)

The method according to claim 41, wherein the therapeutically effective amount is between about 10 to about 1×1016 TCID50/kg of the patient's body weight.

### Claim 52 (depends on 41)

The method according to claim 41, wherein the therapeutically effective amount is between about 10 to about 1×1016 total particles of the agent.