# US 2019/0169270 A1 · Compositions and methods for inhibiting endogenous immunoglobulin genes and producing transgenic human idiotype antibodies

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- Number: US 2019/0169270 A1
- Document ID: US20190169270A1
- Status: Published application
- Kind: A1
- Application number: 16/127,065
- Filed: 2018-09-10
- Published: 2019-06-06
- Earliest claimed: 2007-06-01
- Assignees: Open Monoclonal Technology, Inc.
- Applicants: Open Monoclonal Technology, Inc.
- Inventors: Roland BUELOW
- Web page: https://patentgrep.com/patent/US20190169270A1

## CPC

- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- A01K 67/0276: Knock-out vertebrates
- A01K 67/0278: Knock-in vertebrates, e.g. humanised vertebrates
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- C12N 5/0609: {Oocytes, oogonia (fertilised oocytes C12N5/0604)}
- C12N 9/22: Ribonucleases {[RNase]; Deoxyribonucleases [DNase]}
- C12N 15/8509: {for producing genetically modified animals, e.g. transgenic}
- A01K 2207/15: Humanized animals
- A01K 2217/072: maintaining or altering function, i.e. knock in
- A01K 2217/075: inducing loss of function, i.e. knock out
- A01K 2267/01: Animal expressing industrially exogenous proteins
- C07K 2317/14: Specific host cells or culture conditions, e.g. components, pH or temperature
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C12N 2015/8518: {expressing industrially exogenous proteins, e.g. for pharmaceutical use, human insulin, blood factors, immunoglobulins, pseudoparticles}
- C12N 2510/00: Genetically modified cells
- 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)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The invention relates to transgenic animals lacking endogenous Ig and capable of producing transgenic antibodies, as well as methods of making the same. The invention further relates to Methods for producing transgenic antibodies in such animals, and transgenic antibodies so produced.

## Claims

### Claim at position 1

1-34. (canceled)

### Claim 35

A chimeric monoclonal antibody comprising a non-human IgG constant region, a light chain and/or heavy chain, and a human idiotype, and wherein the non-human constant region comprises a rat IgG CH2 and CH3 domain.

### Claim 36 (depends on 35)

The chimeric monoclonal antibody of claim 35, wherein the non-human constant region further comprises a human IgG CH1 domain.

### Claim 37 (depends on 35)

The chimeric monoclonal antibody of claim 35, wherein the monoclonal antibody comprises a heavy chain and a light chain.

### Claim 38 (depends on 35)

The chimeric monoclonal antibody of claim 35, wherein the monoclonal antibody is a heavy chain only antibody.

### Claim 39 (depends on 35)

The chimeric monoclonal antibody of claim 35, wherein the non-human constant region comprises an IgG CH2 and CH3 domain and lacks a CH1 domain.

### Claim 40

A polyclonal antiserum comprising a plurality of chimeric antibodies, wherein the individual chimeric antibodies comprise a non-human IgG constant region, a heavy chain and/or light chain, and a human idiotype, and wherein the non-human constant region comprises a rat IgG CH2 and CH3 domain.

### Claim 41 (depends on 40)

The polyclonal antiserum of claim 40, wherein the non-human constant region further comprises a human IgG CH1 domain.

### Claim 42 (depends on 40)

The polyclonal antiserum of claim 40, wherein the individual chimeric antibodies comprise a heavy chain and a light chain.

### Claim 43 (depends on 40)

The polyclonal antiserum of claim 40, wherein the individual chimeric antibodies are heavy chain only antibodies.

### Claim 44 (depends on 40)

The polyclonal antiserum of claim 40, wherein the non-human constant region comprises an IgG CH2 and CH3 domain and lacks a CH1 domain.

### Claim 45 (depends on 40)

The polyclonal antiserum of claim 40, wherein the antiserum is:
a. a bird antiserum;
b. a chicken antiserum;
c. a weasel antiserum;
d. a rodent antiserum; or
e. a rat antiserum.

### Claim 46

A diversified repertoire of chimeric immunoglobulins, wherein the individual chimeric immunoglobulins comprise a non-human IgG constant region, a heavy chain and/or light chain, and a human idiotype, and wherein the non-human constant region comprises a rat IgG CH2 and CH3 domain.

### Claim 47 (depends on 46)

The diversified repertoire of claim 46, wherein the non-human constant region further comprises a human IgG CHI domain.

### Claim 48 (depends on 46)

The diversified repertoire of claim 46, wherein the individual chimeric antibodies comprise a heavy chain and a light chain.

### Claim 49 (depends on 46)

The diversified repertoire of claim 46, wherein the individual chimeric antibodies are heavy chain only antibodies.

### Claim 50 (depends on 46)

The diversified repertoire of claim 46, wherein the non-human constant region comprises an IgG CH2 and CH3 domain and lacks a CH1 domain.

### Claim 51 (depends on 46)

The diversified repertoire of claim 46, wherein the repertoire is in a transgenic non-human animal which is nullizygous for endogenous Ig light chain loci and/or endogenous heavy chain loci.

### Claim 52 (depends on 51)

The diversified repertoire of claim 51, wherein the transgenic non-human animal comprises an artificial Ig locus comprising:
a. an artificial constant region gene;
b. at least one human V gene segment;
c. one or more D gene segments; and
d. one or more J gene segments.

### Claim 53 (depends on 51)

The diversified repertoire of claim 51, wherein the transgenic non-human animal is selected from the group consisting of a bird, a rodent, a chicken, a weasel, a rat, and a mouse.

### Claim 54

A nucleic acid encoding a chimeric monoclonal antibody comprising a non-human IgG constant region, a heavy chain and/or light chain, and a human idiotype, and wherein the non-human constant region comprises a rat IgG CH2 and CH3 domain.

### Claim 55 (depends on 54)

The nucleic acid of claim 54, wherein the non-human IgG constant region encoded by the nucleic acid comprises a human IgG CH1 domain.

### Claim 56 (depends on 54)

The nucleic acid of claim 54, wherein the nucleic acid encodes a heavy chain only antibody.

### Claim 57 (depends on 54)

The nucleic acid of claim 54, wherein the nucleic acid encodes a non-human constant region that comprises an IgG CH2 and CH3 domain and lacks a CH1 domain.

### Claim 58 (depends on 54, 55, 56, 57)

A host cell comprising the nucleic acid of any one of claims 54 to 57.

### Claim 59 (depends on 35, 36, 37, 38, 39)

A chimeric antibody according to any one of claims 35 to 39, which is derived from a transgenic animal that comprises an artificial Ig locus comprising an artificial constant region (C) gene encoding a rat IgG CH2 and CH3 domain and optionally a human IgG CH1 domain.

### Claim 60 (depends on 59)

The chimeric monoclonal antibody of claim 59, wherein the transgenic animal from which the chimeric monoclonal antibody is derived comprises an inactivated endogenous Ig locus.

### Claim 61 (depends on 60)

The chimeric monoclonal antibody of claim 60, wherein the transgenic animal from which the chimeric monoclonal antibody is derived comprises at least one genomic meganuclease expression construct.

### Claim 62 (depends on 46, 47, 48, 49, 50, 51, 52, 53)

A diversified repertoire of chimeric immunoglobulins according to any one of claims 46 to 53, which is derived from a transgenic animal that comprises an artificial Ig locus comprising an artificial constant region (C) gene encoding a rat IgG CH2 and CH3 domain and optionally a human IgG CH1 domain.

### Claim 63 (depends on 62)

The diversified repertoire of claim 62, wherein the transgenic animal from which the individual chimeric antibodies are derived comprises an inactivated endogenous Ig locus.

### Claim 64 (depends on 62)

The diversified repertoire of claim 62, wherein the transgenic animal from which the individual chimeric antibodies are derived comprises at least one genomic meganuclease expression construct.