# US 4,400,376 A · Immunological preparations

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- Number: US 4,400,376 A
- Document ID: US4400376A
- Status: Granted
- Kind: A
- Application number: 06/224,565
- Filed: 1980-11-17
- Granted: 1983-08-23
- Earliest claimed: 1979-03-27
- Assignees: National Research Development Corporation
- Inventors: Arnold R. Sanderson
- Web page: https://patentgrep.com/patent/US4400376A

## CPC

- A61K 39/385: Haptens or antigens, bound to carriers
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules}
- A61K 2039/55516: {Proteins; Peptides}
- A61K 2039/6031: {Proteins}
- A61K 2039/605: {MHC molecules or ligands thereof}
- A61K 2039/622: {non-covalent binding}
- Y10S 424/809: involving immunoglobulin or antibody fragment, e.g. fab', fv, fc, heavy chain or light chain
- Y10S 530/806: Antigenic peptides or proteins
- Y10S 530/807: Hapten conjugated with peptide or protein
- Y10S 530/866: involving immunoglobulin or antibody fragment, e.g. fab', fab, fv, fc, heavy chain or light chain
- 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)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

An immunological preparation of an antigenic material in combination with a major histocompatibility complex antigen, which is itself in the form of complex with a protein with which it is normally associated in nature or with a modified form of such protein which retains the epitope thereof intact, said antigenic material being attached to the protein of the complex through antibody to that protein, is disclosed as being useful for the production of an immunogenic response in human or veterinary use.

## Claims

### Claim 1

An antigenic material in combination with a major histocompatibility complex antigen which is is itself in the form of a complex with a protein with which it is normally associated in nature or with a modified form of such protein which retains the epitope thereof intact, said antigenic material being attached to the protein of the complex through antibody to that protein.

### Claim 2

An antigenic material in combination with a human lymphocyte antigen or a non-human, major hostocompatibility complex antigen which is analogous thereto, said human lymphocyte antigen or other major histocompatibility complex antigen itself being in the form of a complex with its associated B2-microglobulin protein or with a modified form of such protein which retains the epitope thereof intact and said antigenic material being attached to the B2-microglobulin of the complex through antibody thereto.

### Claim 3 (depends on 1, 2)

A combination according to claim 1 or 2, wherein the antigenic material is attached to the antibody through a linking group.

### Claim 4 (depends on 1, 2)

A combination according to claim 1 or 2, wherein the antigenic material is a bacterial antigen.

### Claim 5 (depends on 1, 2)

A combination according to claim 1 or 2, wherein the antigenic material is a viral antigen.

### Claim 6 (depends on 1, 2)

A combination according to claim 1 or 2, wherein the antigenic material is a hormone peptide.

### Claim 7 (depends on 1, 2)

A combination according to claim 1 or 2, wherein the antigenic material is attached through antibody to the protein to a major histocompatibility complex antigen-protein complex containing the protein in unmodified form.

### Claim 8 (depends on 1, 2)

A combination according to claim 1 or 2, wherein the antigenic material is attached to the protein or modified protein through a Fab or F(ab').sub.2 fragment of antibody to the protein.

### Claim 9 (depends on 8)

A combination according to claim 8, wherein the attachment is through F (ab').sub.2.

### Claim 10 (depends on 2)

A combination according to claim 2, wherein the antibody is of the IgG type.

### Claim 11 (depends on 3)

A combination according to claim 3, wherein the linking group is derived from a heterobifunctional coupler.

### Claim 12 (depends on 11)

A combination according to claim 11, wherein the linking group is derived from N-(m-maleimidobenzoyl-oxy)-succinimide.

### Claim 13 (depends on 11)

A combination according to claim 11, wherein the antibody has sulphydryl groups which are blocked.

### Claim 14 (depends on 11)

A combination according to claim 11, wherein the major histocompatibility complex antigen has sulphydryl groups which are blocked.

### Claim 15

An immunological preparation for human or veterinary use comprising an antigenic material in combination with a major histocompatibility complex antigen which is itself in the form of a complex with a protein with which it is normally associated in nature or with a modified form of such protein which retains the epitope thereof intact, said antigenic material being attached to the protein of the complex through antibody to that protein, together with a physiologically acceptable diluent or carrier.

### Claim 16 (depends on 15)

A preparation according to claim 15, being for use in humans, wherein said complex is a human lymphocyte antigen-B2-microglobulin complex.

### Claim 17 (depends on 16)

A preparation according to claim 16, wherein the antigenic material is a bacterial toxin or toxoid.

### Claim 18 (depends on 17)

A preparation according to claim 17, wherein the toxoid is diphtheria toxoid.

### Claim 19 (depends on 16)

A preparation according to claim 16, wherein the antigenic material is an influenza virus antigen.

### Claim 20 (depends on 16)

A preparation according to claim 16, wherein the antigenic material is human chorionic gonadotropin.

### Claim 21 (depends on 15)

A preparation according to claim 15, being for veterinary use, wherein said complex is a major histocompatibility complex antigen-B2-microglobulin complex in which the major histocompatibility complex antigen is a non-human antigen analogous to human lymphocyte antigen.

### Claim 22 (depends on 21)

A preparation according to claim 21, wherein the antigenic material is a foot and mouth disease virus antigen and the major histocompatibility complex antigen is bovine or porcine lymphocyte antigen.

### Claim 23

A process for preparing a combination of an antigen with a major histocompatibility complex antigen which comprises reacting together (1) a complex of the major histocompatibility complex antigen with a protein with which it is normally associated in nature or with a modified form of such protein which retains the epitope thereof intact and (2) a combination of said antigenic material with antibody against said protein.

### Claim 24

A method for the production of an immunogenic response in a mammal or bird to an antigenic material which comprises administering thereto said antigenic material in combination with a major histocompatibility complex antigen which is itself in the form of a complex with a protein with which it is normally associated in nature or with a modified form of such protein which retains the epitope thereof intact, said antigenic material being attached to the protein of the complex through antibody to that protein.

### Claim 25 (depends on 24)

A method according to claim 24, wherein the major histocompatibility complex antigen is a human lymphocyte antigen or a non-human major histocompatibility complex antigen which is analogous thereto, said human lymphocyte antigen or other major histocompatibility complex antigen itself being in the form of a complex with its associated B2-microglobulin protein or with a modified form of that protein which retains the epitope thereof intact, and said antigenic material being attached to the B2-microglobulin through antibody thereto.

### Claim 26 (depends on 24, 25)

A method according to claim 24 or 25, wherein the antigenic material is a bacterial antigen.

### Claim 27 (depends on 24, 25)

A method according to claim 24 or 25, wherein the antigenic material is a viral antigen.

### Claim 28 (depends on 24, 25)

A method according to claim 24 or 25, wherein the antigenic material is a hormone peptide.
