# US 10,117,955 B2 · Methods of aiding in the diagnosis of diseases using anti-IL-6 antibodies

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- Number: US 10,117,955 B2
- Document ID: US10117955B2
- Status: Granted
- Kind: B2
- Application number: 15/276,272
- Filed: 2016-09-26
- Published: 2017-04-27
- Granted: 2018-11-06
- Earliest claimed: 2008-11-25
- Assignees: Alderbio Holdings LLC
- Applicants: Alderbio Holdings LLC
- Inventors: Leon Garcia-Martinez; Anne Elisabeth Carvalho Jensen; Katie Olson Anderson; Benjamin H. Dutzar; John A. Latham; Brian R. Kovacevich; Jeffrey T. L. Smith; Mark Litton; Randall C. Schatzman
- Web page: https://patentgrep.com/patent/US10117955B2

## CPC

- A61K 51/1033: {against receptors for cytokines, lymphokines or interferons}
- A61K 49/0058: {Antibodies}
- C07K 16/248: {IL-6}
- G01N 33/6869: {Interleukin}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/515: Complete light chain, i.e. VL + CL
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- G01N 2333/5412: IL-6
- G01N 2800/7095: Inflammation
- 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
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention is directed to therapeutic methods using IL-6 antagonists such as an Ab1 antibody or antibody fragment having binding specificity for IL-6 to prevent or treat disease or to improve survivability or quality of life of a patient in need thereof. In preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level, reduced serum albumin level, elevated D-dimer or other coagulation cascade related protein(s), cachexia, fever, weakness and/or fatigue prior to treatment. The subject therapies also may include the administration of other actives such as chemotherapeutics, anti-coagulants, statins, and others.

## Claims

### Claim 1

A method of aiding in the diagnosis of a disease or condition associated with elevated interleukin 6 (“IL-6”), comprising detecting for the presence of elevated amounts of IL-6 in a biological sample of a subject, and if said biological sample is determined to comprise elevated IL-6 levels identifying said subject as one having or suspected of having a disease associated with elevated IL-6, wherein said detection is effected by:
(i) contacting a biological sample of the patient putatively having a condition associated with elevated IL-6 with an amount of an anti-IL-6 antibody or antibody fragment, whereby said amount of antibody or antibody fragment binds to any IL-6 in the biological sample, wherein the antibody or antibody fragment comprises: a variable light chain polypeptide comprising: a polypeptide having at least 90% identity to SEQ ID NO: 709, and a variable heavy chain polypeptide comprising: a polypeptide having at least 90% identity to SEQ ID NO: 657, further wherein said anti-IL-6 antibody or antibody fragment comprises the variable light chain complementarity determining region (CDR) polypeptides of SEQ ID NO:4, 5 and 6 and comprises the variable heavy chain complementarity determining region (CDR) polypeptides of SEQ ID NO:7, 8 or 120, and 9 and
(ii) detecting the binding of any IL-6 present in the sample to said anti-IL-6 antibody or antibody fragment in order to determine whether the subject putatively has a condition associated with elevated IL-6.

### Claim 2 (depends on 1)

The method of claim 1, wherein the light chain possesses at least 95% sequence identity to the light chain polypeptide comprised in SEQ ID NO: 709.

### Claim 3 (depends on 1)

The method of claim 1, wherein the heavy chain possesses at least 95% sequence identity to the heavy chain polypeptide comprised in SEQ ID NO: 657.

### Claim 4 (depends on 1)

The method of claim 1, wherein the light chain possesses at least 97% sequence identity to the light chain polypeptide comprised in SEQ ID NO: 709.

### Claim 5 (depends on 1)

The method of claim 1, wherein the heavy chain possesses at least 97% sequence identity to the heavy chain polypeptide comprised in SEQ ID NO: 657.

### Claim 6 (depends on 1)

The method of claim 1, wherein the light chain possesses at least 99% sequence identity to the light chain polypeptide comprised in SEQ ID NO: 709.

### Claim 7 (depends on 1)

The method of claim 1, wherein the heavy chain possesses at least 99% sequence identity to the heavy chain polypeptide comprised in SEQ ID NO: 657.

### Claim 8 (depends on 1)

The method of claim 1, wherein the light chain possesses 100% sequence identity to the light chain polypeptide comprised in SEQ ID NO: 709.

### Claim 9 (depends on 1)

The method of claim 1, wherein the heavy chain possesses 100% sequence identity to the heavy chain polypeptide comprised in SEQ ID NO: 657.

### Claim 10 (depends on 1)

The method of claim 1 wherein said antibody comprises light chain CDR1, CDR2 and CDR3 polypeptides and heavy chain CDR1, CDR2 and CDR3 identical to those on SEQ ID NO:4, 5 and 6 and SEQ ID NO:7, 120 and 9 respectively.

### Claim 11 (depends on 1)

The method of claim 1 wherein said antibody comprises light chain CDR1, CDR2 and CDR3 polypeptides and heavy chain CDR1, CDR2 and CDR3 polypeptides identical to those on SEQ ID NO:4, 5 and 6 and SEQ ID NO:7, 8 and 9 respectively.

### Claim 12 (depends on 1)

The method of claim 1 wherein said biological sample is selected from sera, plasma, urine, saliva, mucous, pleural fluid, synovial fluid and spinal fluid.

### Claim 13 (depends on 1)

The method of claim 1 wherein said biological sample is sera or plasma.

### Claim 14 (depends on 1)

The method of claim 1 wherein said detection is effected in vitro.

### Claim 15 (depends on 1)

The method of claim 1 wherein said detection is effected in vivo.

### Claim 16 (depends on 1)

The method of claim 1 wherein said method further includes the detection of a clinical marker other than IL-6.

### Claim 17 (depends on 16)

The method of claim 16, wherein the other clinical marker is a compound correlated to inflammation.

### Claim 18 (depends on 1)

The method of claim 1 wherein the antibody is selected from a human, humanized, single chain, or chimeric antibody and the antibody fragment is selected from a Fab, Fab′, F(ab′)2, Fv, or scFv.

### Claim 19 (depends on 1)

The method claim 1 wherein the disease or condition associated with elevated IL-6 is selected from cancer, a disease or condition associated with hypercoagulation, a disease or condition associated with elevated serum CRP, a disease or condition associated with hypoalbuminemia, an inflammatory disorder, a viral disorder, a wasting syndrome, an autoimmune disorder or any combination thereof.