# US 10,946,036 B2 · Use of myostatin inhibitors and combination therapies

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,946,036 B2
- Document ID: US10946036B2
- Status: Granted
- Kind: B2
- Application number: 16/308,007
- Filed: 2017-06-13
- Published: 2019-08-22
- Granted: 2021-03-16
- Earliest claimed: 2016-06-13
- Assignees: Scholar Rock, Inc.
- Applicants: Scholar Rock, Inc.
- Inventors: Kimberly Long; Adriana Donovan; Yung Chyung; Michelle Straub
- Web page: https://patentgrep.com/patent/US10946036B2

## CPC

- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 31/501: not condensed and containing further heterocyclic rings
- A61K 31/575: substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
- A61K 31/7125: Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- C07K 16/22: against growth factors {; against growth regulators}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/567: Framework region [FR]
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

The present disclosure relates to the treatment of muscle conditions, such as SMA, with the use of an agent that inhibits myostatin signaling. The disclosure includes combination therapies that include a myostatin inhibitor and a neuronal corrector.

## Claims

### Claim 1

A method of treating a neuromuscular disease in a subject, the method comprising administering to the subject a myostatin inhibitor and a neuronal corrector therapy in amounts effective to treat the neuromuscular disease,
wherein:
i) the neuromuscular disease affects a target muscle that is in an anabolic state;
ii) the subject has impaired neurological signaling between a motor neuron and a target muscle, wherein the target muscle has retained or regained at least partial functional innervation by the motor neuron; and
iii) the neuromuscular disease affects a target muscle that is enriched with type II fibers;
wherein the subject receives the myostatin inhibitor and the neuronal corrector therapy within six months of one another;
wherein the neuronal corrector therapy comprises an agent capable of correcting a neuronal defect in the motor neuron; and
wherein the neuromuscular disease is spinal muscular atrophy (SMA).

### Claim 2 (depends on 1)

The method of claim 1, wherein the SMA is type I SMA, type II SMA, or type III SMA.

### Claim 3 (depends on 1)

The method of claim 1, wherein the subject is a pediatric subject or a young adult who is still growing and anabolically active.

### Claim 4 (depends on 1)

The method of claim 1, wherein the myostatin inhibitor inhibits cleavage of a myostatin prodomain, inhibits release of a mature myostatin growth factor, and/or inhibits activation of a pro or latent myostatin to a mature myostatin.

### Claim 5 (depends on 1)

The method of claim 1, wherein the myostatin inhibitor is administered in an amount effective to:
a) delay or alleviate muscle atrophy;
b) delay loss of α-motor neurons;
c) prevent or delay expression of immature muscle markers;
d) prevent, alleviate, or delay intramuscular fat deposits characterized by fatty replacement of muscle tissue;
e) increase an Expanded Hammersmith Functional Motor Scale score by ≥1 points as compared to untreated control, or, by ≥1 points from baseline measured prior to treatment;
f) delay progressive decrease of an Expanded Hammersmith Functional Motor Scale over a period of 12 months, 24 months, or 36 months;
g) increase a CHOP INTEND score by ≥1 points as compared to untreated control; and/or
h) increase a MFM-32 score by at least 1 points as compared to untreated control.

### Claim 6 (depends on 1)

The method of claim 1, wherein the neuronal corrector therapy comprises an SMN corrector and/or an anabolic stimulator.

### Claim 7 (depends on 1)

The method of claim 1, wherein the neuronal defect in the motor neuron is a genetic defect.

### Claim 8

A method of treating spinal muscular atrophy (SMA) in a subject, the method comprising:
(i) selecting a subject, wherein the subject has SMA and is a pediatric subject or a young adult who is still growing and anabolically active; and
(ii) administering to the subject a selective myostatin inhibitor and an SMN corrector therapy in amounts effective to treat SMA.

### Claim 9 (depends on 8)

The method of claim 8, wherein the SMA is type I SMA, type II SMA, or type III SMA.

### Claim 10 (depends on 8)

The method of claim 8, wherein the myostatin inhibitor and the SMN corrector therapy are administered concurrently or within six months of one another.

### Claim 11 (depends on 8)

The method of claim 8, wherein the SMN corrector therapy comprises a splice modifier.

### Claim 12 (depends on 8)

The method of claim 8, wherein the SMN corrector therapy comprises an SMN gene replacement or gene therapy.

### Claim 13 (depends on 8)

The method of claim 8, wherein the SMN corrector therapy comprises an SMN transcription enhancer.

### Claim 14 (depends on 8)

The method of claim 8, wherein the SMN corrector therapy comprises an SMN protein translation enhancer.

### Claim 15 (depends on 8)

The method of claim 8, wherein the SMN corrector therapy comprises an SMN protein stabilizer.

### Claim 16

A method of treating spinal muscular atrophy (SMA) in a subject, the method comprising:
(i) selecting a subject, wherein the subject: (a) has SMA and is a pediatric subject or a young adult who is still growing and anabolically active; and (b) is on an SMN corrector therapy; and
(ii) administering to the subject a selective myostatin inhibitor in an amount effective to treat SMA.

### Claim 17 (depends on 16)

The method of claim 16, wherein the SMA is type I SMA, type II SMA, or type III SMA.

### Claim 18 (depends on 16)

The method of claim 16, wherein the SMN corrector therapy comprises a splice modifier.

### Claim 19 (depends on 16)

The method of claim 16, wherein the SMN corrector therapy comprises an SMN gene replacement or gene therapy.

### Claim 20 (depends on 16)

The method of claim 16, wherein the SMN corrector therapy comprises an SMN transcription enhancer.

### Claim 21 (depends on 16)

The method of claim 16, wherein the SMN corrector therapy comprises an SMN protein translation enhancer.

### Claim 22 (depends on 16)

The method of claim 16, wherein the SMN corrector therapy comprises an SMN protein stabilizer.