# US 12,600,795 B2 · Oligomeric IgG for immunotherapeutics and diagnostics

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- Number: US 12,600,795 B2
- Document ID: US12600795B2
- Status: Granted
- Kind: B2
- Application number: 18/821,716
- Filed: 2024-08-30
- Published: 2025-06-26
- Granted: 2026-04-14
- Earliest claimed: 2023-12-26
- Assignees: Medicovestor, Inc.
- Applicants: Medicovestor, Inc.
- Inventors: Seah Lim
- Web page: https://patentgrep.com/patent/US12600795B2

## CPC

- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate}
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/32: against translation products of oncogenes
- C07K 16/468: {Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies}
- C07K 2317/14: Specific host cells or culture conditions, e.g. components, pH or temperature
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/35: Valency
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/565: Complementarity determining region [CDR]
- 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

This disclosure relates to dimeric immunotherapeutics that comprise an IgG that is crosslinked with a disulfide bond. The IgG may include two heavy chains including a cysteine mutation that forms the disulfide bond. The dimeric immunotherapeutics are formed by increasing the concentration of the IgG such that spontaneous dimerization via the formation of disulfide bonds between the IgG molecules occurs over time.

## Claims

### Claim 1

An oligomeric immunotherapeutic, comprising:
at least two first IgGs that each comprise a first light chain, a first heavy chain, a second light chain, and a second heavy chain, which each have an amino acid sequence numbered according to the EU numbering system;
the amino acid sequences of the at least two first IgGs are identical;
the amino acid sequences of the first heavy chain of the at least two first IgGs each include a mutation of a native amino acid to a cysteine;
the cysteine of the amino acid sequence of the first heavy chain of the at least two first IgGs form a disulfide bond with each other;
the amino acid sequences of the second heavy chain of the at least two first IgGs each lack the mutation;
the at least two first IgGs are both chimeric human IgG1s;
the native amino acid is S444; and
the mutation is S444C.

### Claim 2

An oligomeric immunotherapeutic, comprising:
at least two first IgGs that each comprise a first light chain, a first heavy chain, a second light chain, and a second heavy chain, which each have an amino acid sequence numbered according to the EU numbering system;
the amino acid sequences of the at least two first IgGs are identical;
the amino acid sequences of the first heavy chain of the at least two first IgGs each include a mutation of a native amino acid to a cysteine;
the cysteine of the amino acid sequence of the first heavy chain of the at least two first IgGs form a disulfide bond with each other; and
the amino acid sequences of the second heavy chain of the at least two first IgGs each lack the mutation.

### Claim 3 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the at least two first IgGs are both chimeric human IgG1s;
the native amino acid is S444;
the mutation is S444C.

### Claim 4 (depends on 3)

The oligomeric immunotherapeutic of claim 3, wherein:
the amino acid sequences of the first heavy chain of the at least two first IgGs each include a F405L mutation;
the amino acid sequences of the second heavy chain of the at least two first IgGs each include a K409R mutation;
the first heavy chain of the at least two first IgGs and the second heavy chain of the at least two first IgGs each comprise a heavy chain variable region that has an identical amino acid sequence; and
the first light chain of the at least two first IgGs and the second light chain of the at least two first IgGs each comprise a light chain variable region that has an identical amino acid sequence.

### Claim 5 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the first heavy chain of the at least two first IgGs and the second heavy chain of the at least two first IgGs each comprise a VH CDR1 region comprising an amino acid sequence that is identical to SEQ ID NO: 5;
the first heavy chain of the at least two first IgGs and the second heavy chain of the at least two first IgGs each comprise a VH CDR2 region comprising an amino acid sequence that is identical to SEQ ID NO: 6;
the first heavy chain of the at least two first IgGs and the second heavy chain of the at least two first IgGs each comprise a VH CDR3 region comprising an amino acid sequence that is identical to SEQ ID NO: 7;
the first light chain of the at least two first IgGs and the second heavy chain of the at least two first IgGs each comprise a VL CDR1 region comprising an amino acid sequence that is identical to SEQ ID NO: 8;
the first light chain of the at least two first IgGs and the second heavy chain of the at least two first IgGs each comprise a VL CDR2 region comprising an amino acid sequence that is identical to SEQ ID NO: 9; and
the first light chain of the at least two first IgGs and the second heavy chain of the at least two first IgGs each comprise a VL CDR3 region comprising an amino acid sequence that is identical to SEQ ID NO: 10.

### Claim 6 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the amino acid sequence of the first light chain of the at least two first IgGs is identical to SEQ ID NO: 4;
the amino acid sequence of the second light chain of the at least two first IgGs is identical to SEQ ID NO: 4;
the amino acid sequence of the first heavy chain of the at least two first IgGs is identical to SEQ ID NO: 3; and
the amino acid sequence of the second heavy chain of the at least two first IgGs is identical to SEQ ID NO: 3.

### Claim 7 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the amino acid sequences of the first light chain of the at least two first IgGs and the second light chain of the at least two first IgGs are identical; and
the amino acid sequences of the first heavy chain of the at least two first IgGs and the second heavy chain of the at least two first IgGs each have at least 90 percent sequence identity.

### Claim 8 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein the amino acid sequences of the first light chain of the at least two first IgGs and the second light chain of the at least two first IgGs are identical.

### Claim 9 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein the amino acid sequences of the first heavy chain of the at least two first IgGs and the second heavy chain of the at least two first IgGs each have at least 90 percent sequence identity.

### Claim 10 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the first heavy chain of the at least two first IgGs and the second heavy chain of the at least two first IgGs each comprise a heavy chain variable region that has an identical amino acid sequence; and
the first light chain of the at least two first IgGs and the second light chain of the at least two first IgGs each comprise a light chain variable region that has an identical amino acid sequence.

### Claim 11 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the at least two first IgGs are both chimeric human IgG4s;
the amino acid sequences of the first heavy chain of the at least two first IgGs each include an arginine at amino acid position 409 and a leucine at amino acid position 405; and
the amino acid sequences of the second heavy chain of the at least two first IgGs each include a lysine at amino acid position 409 and a phenylalanine at amino acid position 405.

### Claim 12 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the at least two first IgGs are both chimeric human IgG4s;
the amino acid sequences of the first heavy chain of the at least two first IgGs each include a lysine at amino acid position 409 and a phenylalanine at amino acid position 405; and
the amino acid sequences of the second heavy chain of the at least two first IgGs each include an arginine at amino acid position 409 and a leucine at amino acid position 405.

### Claim 13 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the at least two first IgGs are both chimeric human IgG1s;
the native amino acid is S444;
the mutation is S444C;
the amino acid sequences of the first light chain of the at least two first IgGs and the second light chain of the at least two first IgGs are identical; and
the amino acid sequences of the first heavy chain of the at least two first IgGs and the second heavy chain of the at least two first IgGs each have at least 90 percent sequence identity.

### Claim 14 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the at least two first IgGs are both chimeric human IgG1s;
the native amino acid is S444;
the mutation is S444C;
the amino acid sequences of the first heavy chain of the at least two first IgGs each include a F405L mutation; and
the amino acid sequences of the second heavy chain of the at least two first IgGs each include a K409R mutation.

### Claim 15 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the at least two first IgGs are both chimeric human IgG1s;
the native amino acid is S444;
the mutation is S444C;
the amino acid sequences of the first heavy chain of the at least two first IgGs each include a K409R mutation; and
the amino acid sequences of the second heavy chain of the at least two first IgGs each include a F405L mutation.

### Claim 16 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the at least two first IgGs are both chimeric human IgG1s;
the amino acid sequences of the first heavy chain of the at least two first IgGs each include a F405L mutation; and
the amino acid sequences of the second heavy chain of the at least two first IgGs each include a K409R mutation.

### Claim 17 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the at least two first IgGs are both chimeric human IgG1s;
the amino acid sequences of the first heavy chain of the at least two first IgGs each include a K409R mutation; and
the amino acid sequences of the second heavy chain of the at least two first IgGs each include a F405L mutation.

### Claim 18 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the at least two first IgGs are both chimeric human IgG1s;
the native amino acid is S444; and
the mutation is S444C.

### Claim 19 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the amino acid sequences of the first heavy chain of the at least two first IgGs each include an arginine at amino acid position 409 and a leucine at amino acid position 405; and
the amino acid sequences of the second heavy chain of the at least two first IgGs each include a lysine at amino acid position 409 and a phenylalanine at amino acid position 405.

### Claim 20 (depends on 2)

The oligomeric immunotherapeutic of claim 2, wherein:
the amino acid sequences of the first heavy chain of the at least two first IgGs each include a lysine at amino acid position 409 and a phenylalanine at amino acid position 405; and
the amino acid sequences of the second heavy chain of the at least two first IgGs each include an arginine at amino acid position 409 and a leucine at amino acid position 405.
