# US 10,369,195 B2 · Methods and compositions for preventing and treating damage to the heart

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- Number: US 10,369,195 B2
- Document ID: US10369195B2
- Status: Granted
- Kind: B2
- Application number: 15/666,456
- Filed: 2017-08-01
- Published: 2018-02-15
- Granted: 2019-08-06
- Earliest claimed: 2016-08-09
- Assignees: MandalMed, Inc.; The Regents of the University of California
- Applicants: MandalMed, Inc.; The Regents of the University of California
- Inventors: Constance M. John; Meenakshi Gaur; Matthew L. Springer; Xiaoyin Wang
- Web page: https://patentgrep.com/patent/US10369195B2

## CPC

- A61K 38/1732: {Lectins}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61K 9/0021: {Intradermal administration, e.g. through microneedle arrays or needleless injectors}
- 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

Provided herein are methods and compositions for preventing and treating damage to the heart subsequent to myocardial infarction (MI) resulting from harmful fibrotic remodeling, thereby improving cardiac function and reducing mortality from subsequent heart failure.

## Claims

### Claim 1

A method of reducing infarct size following myocardial infarction (MI) in a human subject comprising administering to the subject an effective dose of Galectin-3C (Gal-3C) beginning 4 days post MI, wherein the Gal-3C comprises the amino acid sequence of SEQ ID NO:3, wherein the effective dose of Gal-3C is 0.25 mg per kg to 0.35 mg per kg of body weight of the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein heart function is improved as shown by an improvement in at least one hemodynamic parameter selected from the group consisting of: ejection fraction (EF), end systolic volume (ESV), end diastolic volume (EDV), mean arterial blood pressure (ABP), left ventricular systolic pressure (LVSP), and left ventricular end diastolic pressure (LVEDP).

### Claim 3 (depends on 1)

The method of claim 1, wherein the administration reduces fibrosis.

### Claim 4 (depends on 1)

The method of claim 1, wherein the administration reduces excess collagen deposition in the heart.

### Claim 5 (depends on 1)

The method of claim 1, wherein the subject has elevated serum galectin-3.

### Claim 6 (depends on 1)

The method of claim 1, wherein the Gal-3C is administered daily.

### Claim 7 (depends on 1)

The method of claim 1, wherein the Gal-3C is administered daily for at least 7 days.

### Claim 8 (depends on 1)

The method of claim 1, wherein the Gal-3C is administered intravenously with a pump.

### Claim 9 (depends on 1)

The method of claim 1, wherein the Gal-3C is administered for a total of 7 days.

### Claim 10 (depends on 1)

The method of claim 1, wherein the effective dose of Gal-3C is 0.32 mg per kg of body weight of the subject.

### Claim 11

A method of reducing infarct size following myocardial infarction (MI) in a human subject, comprising administering to the subject an effective dose of Galectin-3C (Gal-3C) on a daily basis from 14 days to 28 days post MI, wherein the Gal-3C comprises the amino acid sequence of SEQ ID NO:3 and the effective dose of Gal-3C is 0.25 mg per kg to 0.35 mg per kg of body weight of the subject.

### Claim 12 (depends on 1)

The method of claim 1, wherein the Gal-3C is produced by a nucleic acid encoding SEQ ID NO:3.

### Claim 13 (depends on 12)

The method of claim 12, wherein the Gal-3C has not been produced by enzymatic cleavage of a polypeptide comprising SEQ ID NO:1.

### Claim 14 (depends on 1)

The method of claim 1, wherein the Gal-3C has not been produced by enzymatic cleavage of a polypeptide comprising SEQ ID NO:1.

### Claim 15 (depends on 11)

The method of claim 11, wherein the Gal-3C is produced by a nucleic acid encoding SEQ ID NO:3.

### Claim 16 (depends on 15)

The method of claim 15, wherein the Gal-3C has not been produced by enzymatic cleavage of a polypeptide comprising SEQ ID NO:1.

### Claim 17 (depends on 11)

The method of claim 11, wherein the Gal-3C has not been produced by enzymatic cleavage of a polypeptide comprising SEQ ID NO:1.

### Claim 18 (depends on 11)

The method of claim 11, wherein the effective dose of Gal-3C is 0.32 mg per kg of body weight of the subject.

### Claim 19 (depends on 1)

The method of claim 1, wherein the method further comprises measuring infarct size.