# US 10,117,944 B2 · Targeted therapeutics

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- Number: US 10,117,944 B2
- Document ID: US10117944B2
- Status: Granted
- Kind: B2
- Application number: 15/222,145
- Filed: 2016-07-28
- Published: 2017-01-19
- Granted: 2018-11-06
- Earliest claimed: 2014-01-29
- Assignees: Madrigal Pharmaceuticals, Inc.
- Applicants: Madrigal Pharmaceuticals, Inc.
- Inventors: Dinesh U. Chimmanamada; Weiwen Ying
- Web page: https://patentgrep.com/patent/US10117944B2

## CPC

- A61K 47/55: the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug
- A61K 31/365: Lactones
- A61K 31/395: having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K 31/56: Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K 31/69: Boron compounds
- A61P 35/00: Antineoplastic agents
- A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
- 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

## Abstract

The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

## Claims

### Claim 1

A binding moiety-drug conjugate (SDC-TRAP) comprising a binding moiety and an effector moiety, wherein the effector moiety is a proteasome inhibitor selected from the group consisting of bortezomib, ixazomib, and delanzomib, or fragment thereof, the binding moiety binds to HSP90, and the binding moiety and the effector moiety are covalently attached.

### Claim 2 (depends on 1)

The SDC-TRAP of claim 1, wherein the binding moiety is an Hsp90 ligand or a prodrug thereof.

### Claim 3 (depends on 2)

The SDC-TRAP of claim 2, wherein the Hsp90 ligand is an Hsp90 inhibitor.

### Claim 4 (depends on 3)

The SDC-TRAP of claim 3, wherein the Hsp90 inhibitor is selected from the group consisting of ganetespib, geldanamycins, macbecins, tripterins, tanespimycins, and radicicols.

### Claim 5 (depends on 2)

The SDC-TRAP of claim 2, wherein the molecular weight of the SDC-TRAP is less than about 1600 Daltons, less than about 1200 Daltons, less than about 800 Daltons, less than about 600 Daltons or less than about 200 Daltons.

### Claim 6 (depends on 1)

The SDC-TRAP of claim 1, wherein the binding moiety and the effector moiety are covalently attached by a linker.

### Claim 7 (depends on 6)

The SDC-TRAP of claim 6, wherein the linker comprises a cleavable linker.

### Claim 8 (depends on 1)

The SDC-TRAP of claim 1, wherein the SDC-TRAP is able to enter a cell by passive diffusion.

### Claim 9 (depends on 1)

The SDC-TRAP of claim 1, wherein the SDC-TRAP is able to enter a cell by active transport.

### Claim 10

A binding moiety-drug conjugate (SDC-TRAP) or its pharmaceutically acceptable salt, wherein the SDC-TRAP is selected from the group consisting of SDC-TRAP-0236, SDC-TRAP-0237, SDC-TRAP-0238, SDC-TRAP-0239, SDC-TRAP-0240, SDC-TRAP-0241, SDC-TRAP-0242, SDC-TRAP-0243, SDC-TRAP-0244, SDC-TRAP-0245, SDC-TRAP-0246, SDC-TRAP-0247, SDC-TRAP-0248, SDC-TRAP-0249, SDC-TRAP-0250, SDC-TRAP-0251, and SDC-TRAP-0252.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of at least one SDC-TRAP of claim 1, and at least one pharmaceutical excipient.

### Claim 12 (depends on 10)

A pharmaceutical composition comprising a therapeutically effective amount of at least one SDC-TRAP of claim 10, and at least one pharmaceutical excipient.