# US 12,324,826 B2 · Compositions and methods to mitigate or prevent an immune response to an immunogenic therapeutic molecule in non-human primates

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- Number: US 12,324,826 B2
- Document ID: US12324826B2
- Status: Granted
- Kind: B2
- Application number: 17/366,824
- Filed: 2021-07-02
- Published: 2021-10-28
- Granted: 2025-06-10
- Earliest claimed: 2015-12-04
- Assignees: JOMOCO, Corp
- Applicants: Jomoco, Corp
- Inventors: Jack A. Ragheb
- Web page: https://patentgrep.com/patent/US12324826B2

## CPC

- A61K 38/2013: {IL-2}
- C07K 14/7155: {for interleukins [IL]}
- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 2039/505: {comprising antibodies}
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- 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)
- 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 and compositions for preventing an immune response to an immunogenic therapeutic agent [i.e. anti-drug antibody (ADA), a.k.a. anti-therapeutic antibody (ATA)] are disclosed. One of the disclosed methods comprises administering an effective amount of an immunosuppressant such as an Interleukin-2 (IL-2) signaling pathway inhibitor, including an antagonist, super agonist or partial agonist to the cytokine IL-2, to the IL-2 receptor (IL-2R), or to IL-2R signal transduction molecules. Inhibitors can be in the form of antibodies or antibody fragments, peptide inhibitors, fusion molecule, small molecules, antibody/small molecule conjugates. Administration of a given inhibitor can decrease the incidence and/or magnitude of an immune response or prevent an immune response, including an antibody response, to a potentially immunogenic therapeutic agent in a non-human primate (NHP). Some of the disclosed methods produce a tolerizing effect in NHPs.

## Claims

### Claim 1

A method of mitigating formation of anti-drug antibodies (ADA) to an immunogenic therapeutic protein in a non-human primate (NHP), the method comprising administering to the NHP an effective amount of a recombinant anti-CD122 monoclonal antibody that inhibits the binding of IL-2 to its cognate receptor, or an antigen-binding fragment thereof, wherein the anti-CD122 monoclonal antibody is Mik-beta-1 (Mikβ1);
wherein at least one dose of the anti-CD122 antibody or antigen-binding fragment thereof is administered to the NHP within 1 day prior to administration of the immunogenic therapeutic protein, concurrently with the immunogenic therapeutic protein, and/or within 1 day after administration of the immunogenic therapeutic protein,
and
wherein administration of the antibody or antigen-binding fragment thereof decreases the formation of ADA to the immunogenic therapeutic protein in the NHP.

### Claim 2 (depends on 1)

The method of claim 1, wherein the anti-CD122 antibody comprises an antigen-binding fragment thereof of Mikβ1 and a NHP sequence.

### Claim 3 (depends on 1)

The method of claim 1 wherein the effective amount of the anti-CD122 antibody or antigen-binding fragment thereof is from about 0.1 mg/kg to about 100 mg/kg of the body weight of the NHP.

### Claim 4 (depends on 1)

The method of claim 1, wherein at least one additional dose of the anti-CD122 antibody or antigen-binding fragment thereof is administered 1 day before, during, and/or 1 day after an additional administration of the immunogenic therapeutic protein.

### Claim 5 (depends on 1)

The method of claim 1, wherein the anti-CD122 antibody or an antigen-binding fragment thereof is administered at an interval equal to or less than the apparent half-life of the antibody in NHPs.

### Claim 6 (depends on 1)

The method of claim 1, wherein the anti-CD122 antibody or antigen-binding fragment thereof is administered once a day or once a week.

### Claim 7 (depends on 1)

The method of claim 1, wherein the anti-CD122 antibody or antigen-binding fragment thereof is administered once bi-weekly, once every three weeks, or once every month.

### Claim 8 (depends on 1)

The method of claim 1, wherein the anti-CD122 antibody or antigen-binding fragment thereof is administered every other day, every three days, every 5 days, once every 10 days, every two weeks, or every 20 days.

### Claim 9 (depends on 1)

The method of claim 1, wherein the anti-CD122 antibody or antigen-binding fragment thereof is administered as often or as little as is necessary to maintain receptor occupancy at a level that mitigates or prevents formation of ADA.

### Claim 10 (depends on 1)

The method of claim 1, wherein the immunogenic therapeutic protein is administered in more than one dose, wherein subsequent doses are separated by hours, days, weeks, or months.

### Claim 11 (depends on 1)

The method of claim 1, wherein the anti-CD122 antibody or antigen-binding fragment thereof is administered to the NHP within 1 day prior to administration of each dose of the immunogenic therapeutic protein, concurrently with each dose of the immunogenic therapeutic protein, and/or within 1 day after administration of each dose of the immunogenic therapeutic protein.

### Claim 12 (depends on 1)

The method of claim 1, further comprising administering to the NHP an effective dose of rapamycin.

### Claim 13 (depends on 12)

The method of claim 12, wherein the rapamycin is administered daily or every other day.

### Claim 14 (depends on 12)

The method of claim 12, wherein the concentration of rapamycin is maintained at a trough level within the range of 4-12 ng/mL.