# US 2014/0193413 A1 · Antibodies binding to phosphorylcholine (pc) and/or pc conjugates

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- Number: US 2014/0193413 A1
- Document ID: US20140193413A1
- Status: Published application
- Kind: A1
- Application number: 14/235,970
- Filed: 2012-08-08
- Published: 2014-07-10
- Earliest claimed: 2011-08-09
- Assignees: Dyax Corp.; Athera Biotechnologies AB
- Inventors: Knut Pettersson; Ola Camber; Dan Sexton; Andrew E. Nixon
- Web page: https://patentgrep.com/patent/US20140193413A1

## CPC

- C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids}
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 37/02: Immunomodulators
- C07K 16/18: against material from animals or humans
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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)

## Abstract

The present disclosure relates to an antibody or antibody fragment capable of binding to phosphorylcholine and/or a phosphorylcholine conjugate, wherein the antibody or antibody fragment comprises a variable heavy chain (VH) domain and/or a variable light chain (VL) domain, and wherein (a) the VH domain comprises complementarity determining regions (CDRs) selected from the group consisting of: a CDR1 sequence having identity to the sequence of SEQ ID NO: 7; a CDR2 sequence having identity to the sequence of SEQ ID NO: 8; and a CDR3 sequence having identity to the sequence of SEQ ID NO: 9 or 10; and/or (b) the VL domain comprises CDRs selected from the group consisting of: a CDR4 sequence having identity to the sequence of SEQ ID NO: 11; a CDR5 sequence having identity to the sequence of SEQ ID NO: 12; a CDR6 sequence having identity to the sequence of SEQ ID NO: 13.

## Claims

### Claim 1

An antibody or antibody fragment capable of binding to phosphorylcholine and/or a phosphorylcholine conjugate,
wherein the antibody or antibody fragment comprises a variable heavy chain (VH) domain and/or a variable light chain (VL) domain, and wherein—
(a) the VH domain comprises an amino acid sequence that includes one, two or three complementarity determining regions (CDRs) selected from the group consisting of
a CDR1 sequence comprising an amino acid sequence having at least 20%, 40%, 60%, 80% or 100% sequence identity to the sequence of SEQ ID NO: 7;
a CDR2 sequence comprising an amino acid sequence having at least 5%, 11%, 17%, 23%, 29%, 35%, 41%, 47%, 52%, 58%, 64%, 70%, 76%, 82%, 88%, 94%, or 100% sequence identity to the sequence of SEQ ID NO: 8; and
a CDR3 sequence comprising an amino acid sequence having at least 11%, 22%, 33%, 44%, 55%, 66%, 77%, 88% or 100% sequence identity to the sequence of SEQ ID NO: 9 or 10; and/or
(b) the VL domain comprises an amino acid sequence that includes one, two or three complementarity determining regions (CDRs) selected from the group consisting of:
a CDR4 sequence comprising an amino acid sequence having at least 7.5%, 15%, 23%, 30%, 38%, 46%, 53%, 61%, 69%, 76% 84%, 92% or 100% sequence identity to the sequence of SEQ ID NO: 11;
a CDR5 sequence comprising an amino acid sequence having at least 14%, 28%, 42%, 57%, 71%, 85% or 100% sequence identity to the sequence of SEQ ID NO: 12;
a CDR6 sequence comprising an amino acid sequence having at least 9%, 18%, 27%, 36%, 45%, 54%, 63%, 72%, 81%, 90% or 100% sequence identity to the sequence of SEQ ID NO: 13.

### Claim 2 (depends on 1)

The antibody or antibody fragment of claim 1 wherein the VH domain comprises an amino acid sequence that includes a CDR1 sequence, a CDR2 and a CDR3 sequence as defined by claim 1, and/or the VL domain comprises an amino acid sequence that includes a CDR4 sequence, a CDR5 and a CDR6 sequence as defined by claim 1.

### Claim 3 (depends on 1)

The antibody or antibody fragment of claim 1 wherein:
the VH domain comprises an amino acid sequence that includes the CDR1, CDR2 and CDR3 sequences present in an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 3 or 5 or an amino acid sequence having at least 80%, 85%, 90%, or 95% sequence identity to an amino acid sequence of any of SEQ ID NOs: 1, 3 or 5; and/or
the VL domain comprises an amino acid sequence that includes the CDR4, CDR5 and CDR6 sequences present in an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 4 or 6 or an amino acid sequence having at least 80%, 85%, 90%, or 95% sequence identity to an amino acid sequence of any of SEQ ID NOs: 2, 4 or 6.

### Claim 4 (depends on 1)

The antibody or antibody fragment of claim 1 wherein:
the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 3, or 5 or an amino acid sequence having at least 80%, 85%, 90%, or 95% sequence identity to an amino acid sequence of any of SEQ ID NOs: 1, 3, or 5; and
the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 4, or 6 or an amino acid sequence having at least 80%, 85%, 90%, or 95% sequence identity to an amino acid sequence of any of SEQ ID NOs: 2, 4, or 6.

### Claim 5 (depends on 1)

The antibody or antibody fragment according to claim 1, wherein:
the VH domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity SEQ ID NO:1; and
the VL domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity SEQ ID NO: 2.

### Claim 6 (depends on 1)

The antibody or antibody fragment according to claim 1, wherein:
the VH domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity SEQ ID NO:3; and
the VL domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity SEQ ID NO: 4.

### Claim 7 (depends on 1)

The antibody or antibody fragment according to claim 1, wherein:
the VH domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95% or 100% sequence identity SEQ ID NO:5; and
the VL domain comprises an amino acid sequence having at least 80%, 85%, 95% or 00% sequence identity SEQ ID NO: 6.

### Claim 8 (depends on 1)

The antibody or antibody fragment according to claim 1, wherein the VH domain, the VL domain, or preferably both of the VH and VL domains, comprise an amino acid sequence having 100% sequence identity to the, or one or more (such as all) of each, stated SEQ ID NO.

### Claim 9 (depends on 1)

The antibody or antibody fragment according to claim 1, wherein the VH domain, the VL domain, or both of the VH and VL domains, comprise an amino acid sequence having less than 100%, but at least 80%, 85%, 90%, 95%, sequence identity to the, or one or more (such as all) of each, stated SEQ ID NO.

### Claim 10 (depends on 1)

The antibody or antibody fragment according to claim 1,
wherein the VH domain, the VL domain, or both of the VH and VL domains, comprise an amino acid sequence having less than 100%, but at least 80%, 85%, 90%, 95%, sequence identity to the, or one or more (such as all) of each, stated SEQ ID NC), and wherein
the ability of the antibody or antibody fragment to bind to phosphorylcholine and/or a phosphorylcholine conjugate is equivalent to (that is, at least 80%, 85%, 90% or 95%, of), or greater than, the ability of a corresponding antibody or antibody fragment, wherein the VH domain and the VL domain of the corresponding antibody or antibody fragment each comprise an antigen-binding sequence comprising an amino acid sequence having 100% sequence identity to the, or each, stated SEQ. ID NO.

### Claim 11 (depends on 1)

The antibody or antibody fragment according to claim 1, wherein the VH domain and the VL domain are present in a linear polypeptide sequence.

### Claim 12 (depends on 1)

The antibody or antibody fragment according to claim 1, wherein the VH domain and the VL domain are each present in a separate polypeptide sequence, and preferably wherein the separate polypeptide sequence are directly or indirectly bound together (such as by one or more disulphide bonds between the separate polypeptide sequence).

### Claim 13 (depends on 1)

The antibody according to claim 1, wherein the antibody is a monoclonal antibody.

### Claim 14 (depends on 1)

The antibody fragment according to claim 1, wherein the antibody fragment is a single chain antibody, Fv, scFv, Fab, F(ab′)2, Fab′, Fd, dAb, CDR, or scFv-Fc fragment, a nanobody, and diabody, or any such fragment that has been stabilized such as by PEGylation.

### Claim 15 (depends on 1)

The antibody or antibody fragment according to claim 1, which is a human or humanized antibody or antibody fragment, such as a human or humanized monoclonal antibody.

### Claim 16 (depends on 1)

The antibody or antibody fragment according to claim 1, which is capable of binding to a phosphorylcholine conjugate.

### Claim 17 (depends on 16)

The antibody or antibody fragment according to claim 16, wherein the phosphorylcholine conjugate is a phosphorylcholine moiety linked to a carrier, optionally via a spacer, and preferably the antibody or antibody fragment binds specifically to the phosphorylcholine moiety in the phosphorylcholine conjugate.

### Claim 18

A pharmaceutical composition comprising or consisting essentially of an antibody or an antibody fragment according to any of the preceding claims and a pharmaceutically acceptable carrier or excipient, optionally wherein the only antibodies or antibody fragments present in the composition are those defined by any of the preceding claims.

### Claim at position 19

19-22. (canceled)

### Claim 23 (depends on 1)

A method for prevention, prophylaxis and/or treatment of a mammal, including a human, against atherosclerosis, an atherosclerotic related disease, or ischemic cardiovascular disease, the method comprising the step of administering to the mammal an antibody or antibody fragment according to claim 1.

### Claim 24 (depends on 1)

A method for immunization and prophylaxis, prevention and/or treatment of a subject against Alzheimer's disease, the method comprising the step of administering to the subject an antibody or antibody fragment according to claim 1.

### Claim 25 (depends on 1)

A method for the immunization or prophylaxis against, or the treatment of, metabolic diseases in a mammal, such as a human, the method comprising the step of administering to the mammal an antibody or antibody fragment according to claim 1.

### Claim 26 (depends on 25)

The method according to claim 25, wherein the metabolic disease is a condition selected from the group consisting of metabolic syndrome, insulin resistance, glucose intolerance, hyperglycemia, type I diabetes, type II diabetes, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, and polycystic ovary syndrome (PCOS).

### Claim 27 (depends on 1)

A nucleic acid sequence encoding an antibody or an antibody fragment according to claim 1.

### Claim 28 (depends on 27)

A vector or plasmid comprising the nucleic acid sequence of claim 27.

### Claim 29 (depends on 27)

A host cell comprising the nucleic acid sequence of claim 27.

### Claim 30 (depends on 29)

The host cell of claim 29, wherein the cell is a prokaryotic cell, such as an Escherichia coli cell, or a eukaryotic cell, such as animal, plant, or fungal cell.

### Claim 31 (depends on 29)

The host cell of claim 29, which expresses the nucleic acid sequence to produce an antibody or an antibody fragment.

### Claim 32 (depends on 31)

A method of producing an antibody or an antibody fragment comprising culturing a host cell according to claim 31, and recovering therefrom said antibody or antibody fragment.

### Claim 33 (depends on 1)

A method of preparing a variant of the antibody or antibody fragments of according to claim 1, which variant retains the ability to bind to phosphorylcholine and/or a phosphorylcholine conjugate, the method comprising:
(i) providing a nucleic acid according to encoding the antibody or antibody fragment of claim 1;
introducing one or more nucleotide mutations into the amino acid coding regions of the nucleic acid sequence, optionally within the regions encoding the VH and/or VL domain(s), such that the mutated nucleic acid encodes a variant antibody or antibody fragment having a different amino acid sequence compared to the parent antibody or antibody fragment;
(iii) expressing the variant antibody or antibody fragment that is encoded by the mutated nucleic acid sequence; and
(iv) comparing the ability of the variant antibody or antibody fragment and the parent antibody or antibody fragment to bind to phosphorylcholine and/or a phosphorylcholine conjugate.

### Claim 34 (depends on 33)

The method of claim 33, wherein the step of assessing the ability of the variant antibody or antibody fragment to bind to phosphorylcholine and/or a phosphorylcholine conjugate further comprises selecting those variants that have substantially equal or enhanced ability to bind to phosphorylcholine and/or a phosphorylcholine conjugate compared to the parent.

### Claim 35 (depends on 33)

The method of claim 33, further comprising recovering a nucleic acid molecule that comprises the mutated nucleic acid sequence that encodes the variant antibody or antibody fragment, and optionally transforming a host cell with a composition comprising the recovered nucleic acid molecule and further optionally expressing the variant antibody or antibody fragment from the host cell, and yet further optionally recovering the thus-expressed variant antibody or antibody fragment from the host cell.

### Claim 36 (depends on 35)

The method of claim 35, comprising the step of recovering the thus-expressed variant antibody or antibody fragment from the host cell, and further comprises the step of formulating the recovered variant antibody or antibody fragment into a pharmaceutically acceptable composition.

### Claim 37 (depends on 33)

A variant antibody or antibody fragment obtained or obtainable by the method of claim 33.