# US 12,118,414 B2 · BCL-2 proteins degraders for cancer treatment

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- Number: US 12,118,414 B2
- Document ID: US12118414B2
- Status: Granted
- Kind: B2
- Application number: 16/962,816
- Filed: 2019-01-22
- Published: 2021-03-25
- Granted: 2024-10-15
- Earliest claimed: 2018-01-22
- Assignees: BioVentures, LLC
- Applicants: BioVentures, LLC
- Inventors: Guangrong Zheng; Daohong Zhou; Xuan Zhang; Sajid Khan; Yonghan He; Peiyi Zhang
- Web page: https://patentgrep.com/patent/US12118414B2

## CPC

- A61K 31/635: having a heterocyclic ring, e.g. sulfadiazine
- G06J 1/00: Hybrid computing arrangements
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/14: containing three or more hetero rings
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: containing three or more hetero rings
- C07K 5/06034: {the side chain containing 2 to 4 carbon atoms}
- G06N 3/063: using electronic means
- G06N 5/01: Dynamic search techniques; Heuristics; Dynamic trees; Branch-and-bound
- G06N 5/04: Inference or reasoning models
- G06N 10/00: Quantum computing, i.e. information processing based on quantum-mechanical phenomena
- A61N 5/062: {Photodynamic therapy, i.e. excitation of an agent}
- A61N 5/10: X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence)
- G06N 3/044: Recurrent networks, e.g. Hopfield networks
- G06N 3/047: Probabilistic or stochastic networks
- 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)
- G06J: HYBRID COMPUTING ARRANGEMENTS (optical hybrid computing devices G06E3/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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)
- G06N: COMPUTING ARRANGEMENTS BASED ON SPECIFIC COMPUTATIONAL MODELS
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)

## Abstract

The present disclosure provides compositions and methods for selectively killing cancer cells, wherein the composition comprises a compound of Formula (I). The selective killing of cancer cells occurs with an improved potency and safety profile compared to similar compounds. In particular, the compositions and methods of the invention show reduced platelet toxicity and retained or improved toxicity in cancer cells.

## Claims

### Claim 1

A method of selectively killing one or more cancer cells in a subject in need thereof, the method comprising administering to the subject a composition comprising a therapeutically effective amount of a compound or a salt of the compound, wherein the compound has the following chemical structure:

### Claim 2 (depends on 1)

The method of claim 1 wherein the subject in need is a mammal.

### Claim 3

A method of degrading Bcl-2 proteins in a subject, the method comprising administering a composition comprising a therapeutically effective amount of a compound or a salt of the compound to a subject in need thereof, wherein the compound has the following chemical structure:

### Claim 4 (depends on 2)

The method of claim 2 wherein the composition further comprises a pharmaceutically acceptable excipient.

### Claim 5 (depends on 2)

The method of claim 2, wherein the method further comprises the step of administering a second cancer therapeutic agent.

### Claim 6 (depends on 5)

The method of claim 5, wherein the composition further comprises the second cancer therapeutic agent and wherein the second cancer therapeutic agent is simultaneously administered to the subject in need thereof.

### Claim 7 (depends on 5)

The method of claim 5, wherein the second cancer therapeutic agent is selected from the group consisting of: an alkylating agent, an anti-metabolite, an anti-tumor antibiotic, an anti-cytoskeletal agent, a topoisomerase inhibitor, an anti-hormonal agent, a targeted therapeutic agent, a photodynamic therapeutic agent, or a combination thereof.

### Claim 8

A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a composition comprising a pharmaceutically acceptable excipient and a therapeutically effective amount of a compound or a salt of the compound, wherein the compound has the following chemical structure:

### Claim 9 (depends on 8)

The method of claim 8 wherein the method further comprises administering cancer radiotherapy to the subject.

### Claim 10 (depends on 8)

The method of claim 8, wherein the pharmaceutically acceptable excipient is a diluent, a binder, a filler, a buffering agent, a pH modifying agent, a disintegrant, a dispersant, a preservative, a lubricant, a taste masking agent, a flavoring agent, or a coloring agent.

### Claim 11 (depends on 8)

The method of claim 8, wherein the composition is administered orally, parenterally, or topically.

### Claim 12 (depends on 8)

The method of claim 8, wherein the method further comprises the step of administering a second cancer therapeutic agent.

### Claim 13 (depends on 12)

The method of claim 12, wherein the composition further comprises the second cancer therapeutic agent and wherein the second cancer therapeutic agent is simultaneously administered to the subject in need thereof.

### Claim 14 (depends on 13)

The method of claim 13, wherein the second cancer therapeutic agent is selected from the group consisting of: an alkylating agent, an anti-metabolite, an anti-tumor antibiotic, an anti-cytoskeletal agent, a topoisomerase inhibitor, an anti-hormonal agent, a targeted therapeutic agent, a photodynamic therapeutic agent, or a combination thereof.

### Claim 15 (depends on 3)

The method of claim 3, wherein the method further comprises administering cancer radiotherapy to the subject.

### Claim 16 (depends on 4)

The method of claim 4, wherein the pharmaceutically acceptable excipient is a diluent, a binder, a filler, a buffering agent, a pH modifying agent, a disintegrant, a dispersant, a preservative, a lubricant, a taste masking agent, a flavoring agent, or a coloring agent.

### Claim 17 (depends on 3)

The method of claim 3, wherein the composition is administered orally, parenterally, or topically.

### Claim 18 (depends on 3)

The method of claim 3, wherein the method further comprises the step of administering an additional therapeutic agent, wherein the additional therapeutic agent is an agent for the treatment of cancer.

### Claim 19 (depends on 18)

The method of claim 18, wherein the composition further comprises the additional therapeutic and wherein the additional therapeutic agent is simultaneously administered to the subject in need thereof.

### Claim 20 (depends on 18)

The method of claim 18, wherein the additional therapeutic agent is selected from the group consisting of: an alkylating agent, an anti-metabolite, an anti-tumor antibiotic, an anti-cytoskeletal agent, a topoisomerase inhibitor, an anti-hormonal agent, a targeted therapeutic agent, a photodynamic therapeutic agent, or a combination thereof.