# US 7,744,891 B2 · Soluble lymphotoxin-beta receptors and anti-lymphotoxin receptor and ligand antibodies as therapeutic agents for the treatment of immunological diseases

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- Number: US 7,744,891 B2
- Document ID: US7744891B2
- Status: Granted
- Kind: B2
- Application number: 11/891,847
- Filed: 2007-08-13
- Published: 2008-09-11
- Granted: 2010-06-29
- Earliest claimed: 1996-10-25
- Assignees: Biogen Idec MA Inc.
- Inventors: Jeffrey L. Browning; Paula S. Hochman; Paul D. Rennert; Fabienne Mackay
- Web page: https://patentgrep.com/patent/US7744891B2

## CPC

- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 7/06: Antianaemics
- A61P 19/04: for non-specific disorders of the connective tissue
- A61P 21/04: for myasthenia gravis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/00: Drugs for immunological or allergic disorders
- C07K 14/7151: {for tumor necrosis factor [TNF], for lymphotoxin [LT]}
- C07K 16/241: {Tumor Necrosis Factors}
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- 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)
- C07K 2319/00: Fusion polypeptide
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Compositions and methods comprising “lymphotoxin-β receptor blocking agents” which block lymphotoxin-β receptor signaling and are useful for altering immunological diseases, and particularly antibody mediated immune responses.

## Claims

### Claim 1

A method for reducing the humoral immune response in a subject comprising the step of
administering a pharmaceutical composition which comprises a therapeutically effective amount of a LT-β-R blocking agent selected from the group consisting of: a soluble lymphotoxin-β receptor, an antibody directed against LT-β receptor, and an antibody directed against surface LT ligand to a subject that would benefit from a reduced humoral response, such that a reduced humoral response occurs in the subject.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the LT-β-R blocking agent comprises a soluble lymphotoxin-β receptor having a ligand binding domain that can selectively bind to a surface LT ligand.

### Claim 3 (depends on 2)

The method according to claim 2, wherein the soluble lymphotoxin-β receptor comprises a human immunoglobulin Fc domain.

### Claim 4 (depends on 1)

The method of claim 1, wherein the LT-β-R blocking agent further comprises a pharmaceutically acceptable carrier or adjuvant.

### Claim 5

A method for reducing the association of immune complexes and B cell follicles in a subject comprising administering an amount of an LT-β-R blocking agent selected from the group consisting of: a soluble lymphotoxin-β receptor, an antibody directed against LT-β receptor, and an antibody directed against surface LT ligand to a subject that would benefit from a reduced association of immune complexes and B cell follicles, such that a reduced association of immune complexes and B cell follicles occurs in the subject.

### Claim 6 (depends on 5)

The method of claim 5 wherein the LT-β-R blocking agent comprises a soluble LT-β-R having a ligand binding domain that can selectively bind to a surface LT ligand.

### Claim 7 (depends on 6)

The method of claim 6, wherein said soluble LT-β-R comprises a human immunoglobulin Fc domain.

### Claim 8 (depends on 1)

The method of claim 1, wherein the subject is suffering from an autoimmune disorder.

### Claim 9 (depends on 2)

The method of claim 2, wherein the subject is suffering from an autoimmune disorder.

### Claim 10 (depends on 5)

The method of claim 5, wherein the subject is suffering from an autoimmune disorder.

### Claim 11 (depends on 6)

The method of claim 6, wherein the subject is suffering from an autoimmune disorder.

### Claim 12 (depends on 1)

The method of claim 1, wherein the presentation of antigen on follicular dendritic cells (FDCs) in the subject is reduced.

### Claim 13 (depends on 2)

The method of claim 2, wherein the presentation of antigen on follicular dendritic cells (FDCs) in the subject is reduced.

### Claim 14 (depends on 5)

The method of claim 5, wherein the presentation of antigen on follicular dendritic cells (FDCs) in the subject is reduced.

### Claim 15 (depends on 6)

The method of claim 6, wherein the presentation of antigen on follicular dendritic cells (FDCs) in the subject is reduced.

### Claim 16 (depends on 12)

The method of claim 12, wherein said reduction of the presentation of antigen on FDCs results in a reduction of the immune response in the subject.

### Claim 17 (depends on 16)

The method of claim 16, wherein the blocking agent is administered to the subject prior to the introduction of the antigen into the subject, such that the presentation of antigen on FDCs is reduced, thereby reducing the immune response in the subject.

### Claim 18 (depends on 16)

The method of claim 16, wherein the blocking agent is administered to the subject after association of the FDCs with the antigen, and wherein said blocking agent disrupts the association of the FDCs with the antigen, thereby reducing the immune response in the subject.

### Claim 19 (depends on 13)

The method of claim 13, wherein said reduction of the presentation of antigen on FDCs results in a reduction of the immune response in the subject.

### Claim 20 (depends on 19)

The method of claim 19, wherein the blocking agent is administered to the subject prior to the introduction of the antigen into the subject, such that the presentation of antigen on FDCs is reduced, thereby reducing the immune response in the subject.

### Claim 21 (depends on 19)

The method of claim 19, and wherein the blocking agent is administered to the subject after association of the FDCs with the antigen, wherein said blocking agent disrupts the association of the FDCs with the antigen, thereby reducing the immune response in the subject.

### Claim 22 (depends on 14)

The method of claim 14, wherein said reduction of the presentation of antigen on FDCs results in a reduction of the immune response in the subject.

### Claim 23 (depends on 22)

The method of claim 22, wherein the blocking agent is administered to the subject prior to the introduction of the antigen into the subject, such that the presentation of antigen on FDCs is reduced, thereby reducing the immune response in the subject.

### Claim 24 (depends on 22)

The method of claim 22, wherein the blocking agent is administered to the subject after association of the FDCs with the antigen, wherein said blocking agent disrupts the association of the FDCs with the antigen, thereby reducing the immune response in the subject.

### Claim 25 (depends on 15)

The method of claim 15, wherein said reduction of the presentation of antigen on FDCs results in a reduction of the immune response in the subject.

### Claim 26 (depends on 25)

The method of claim 25, wherein the blocking agent is administered to the subject prior to the introduction of the antigen into the subject, such that the presentation of antigen on FDCs is reduced, thereby reducing the immune response in the subject.

### Claim 27 (depends on 25)

The method of claim 25, wherein the blocking agent is administered to the subject after association of the FDCs with the antigen, and wherein said blocking agent disrupts the association of the FDCs with the antigen, thereby reducing the immune response in the subject.

### Claim 28 (depends on 1)

The method of claim 1, wherein the generation and maintenance of memory B cells in the subject is reduced.

### Claim 29 (depends on 2)

The method of claim 2, wherein the generation and maintenance of memory B cells in the subject is reduced.

### Claim 30 (depends on 5)

The method of claim 5, wherein the generation and maintenance of memory B cells in the subject is reduced.

### Claim 31 (depends on 6)

The method of claim 6, wherein the generation and maintenance of memory B cells in the subject is reduced.

### Claim 32 (depends on 1)

The method according to claim 1, wherein the LT-β-R blocking agent comprises an antibody directed against LT-β receptor.

### Claim 33 (depends on 1)

The method according to claim 1, wherein the LT-β-R blocking agent comprises an antibody directed against surface LT ligand.

### Claim 34 (depends on 5)

The method of claim 5, wherein the LT-β-R blocking agent comprises an antibody directed against LT-β receptor.

### Claim 35 (depends on 5)

The method of claim 5 wherein, wherein the LT-β-R blocking agent comprises an antibody directed against surface LT ligand.