# US 10,946,103 B2 · Methods of treatment using a branched amino terminal pegylated Il-11 composition

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- Number: US 10,946,103 B2
- Document ID: US10946103B2
- Status: Granted
- Kind: B2
- Application number: 16/418,850
- Filed: 2019-05-21
- Published: 2019-12-05
- Granted: 2021-03-16
- Earliest claimed: 2015-03-03
- Assignees: Nansha Biologics (Hong Kong) Limited
- Applicants: Nansha Biologics (Hong Kong) Limited
- Inventors: Kuo-Ming Yu; Qui-Lim Choo; Manson Fok; Johnson Yiu-Nam Lau
- Web page: https://patentgrep.com/patent/US10946103B2

## CPC

- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- 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)}
- A61K 38/2073: {IL-11}
- A61K 45/00: Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 5/38: of the suprarenal hormones
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 19/00: Drugs for skeletal disorders
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/5431: {IL-11}
- 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: 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

Methods are provided for treating an individual with a pharmaceutical preparation that includes a recombinant IL-11 PEGylated at equimolar to low molar excess of PEG to achieve a highly pure monoconjugate preparation, which provides improved half-life in serum while having desirable therapeutic activity and presenting fewer side-effects. Most preferably, the IL-11 is an N-terminally truncated human or humanized IL-11 and has a 20 Kd or 40 Kd branched PEG moiety, Y- or comb-shaped in particular, coupled to the N-terminal amino group. Such compounds are characterized by substantially increased stability in serum and sustained biological activity while exhibiting significantly reduced plasma expansion.

## Claims

### Claim 1

A method of treating a condition responsive to administration of IL-11, comprising:
providing a pharmaceutical composition comprising an IL-11 conjugate prepared by covalently coupling an IL-11 polypeptide chain to a PEG moiety by a process that selectively couples the PEG moiety to the N-terminus of the IL-11, wherein the PEG moiety has an average molecular weight of between 10-50Kd and has at least two branches, and wherein an equimolar to 2-fold molar excess of the PEG moiety relative to the IL-11 is present during coupling, wherein the IL-11 conjugate preparation comprises monosubstituted IL-11 PEG conjugate at a purity of greater than 93%, and wherein the IL-11 polypeptide chain is a human IL-11 or truncated human IL-11 polypeptide chain; and
administering the pharmaceutical composition to an animal.

### Claim 2 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition is formulated for injection.

### Claim 3 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition is provided in an amount to provide a dosage unit of between 10-100 μg/kg on IL-11 PEG conjugate for a pediatric or adult patient.

### Claim 4 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition is lyophilized.

### Claim 5 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition further comprises second pharmaceutically active compound.

### Claim 6 (depends on 5)

The method of claim 5, wherein the second pharmaceutically active compound is a steroid, an agent that stimulates platelet production in bone marrow, an antibody, an analgesic, or anti-inflammatory agent.

### Claim 7 (depends on 1)

The method of claim 1 wherein the pharmaceutical preparation is administered subcutaneously.