# US 2019/0315876 A1 · Antigen Binding Molecules That Bind LIGHT

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- Number: US 2019/0315876 A1
- Document ID: US20190315876A1
- Status: Published application
- Kind: A1
- Application number: 16/256,688
- Filed: 2019-01-24
- Published: 2019-10-17
- Earliest claimed: 2018-01-24
- Assignees: Capella Bioscience Ltd
- Applicants: Capella Bioscience Ltd.
- Inventors: Steve Holmes
- Web page: https://patentgrep.com/patent/US20190315876A1

## CPC

- C07K 16/2875: {against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 (against NGF C07K16/22, against TNF C07K16/241)}
- A61K 39/001136: {Cytokines}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61K 2039/505: {comprising antibodies}
- 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 2317/55: Fab or Fab'
- 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
- 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)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to antigen binding molecules, including antibodies, fragments, and variants thereof, that bind to the TNF-related cytokine LIGHT (TNFSF14). The present invention also relates to methods of use of such antigen binding molecules in treating and/or preventing inflammatory disorders and immune disorders.

## Claims

### Claim 1

An anti-LIGHT antigen binding molecule or an affinity matured mutant, wherein the antigen binding molecule or an affinity matured mutant has a higher affinity for membrane-bound LIGHT compared to soluble LIGHT.

### Claim 2 (depends on 1)

The anti-LIGHT antigen binding molecule or an affinity matured mutant of claim 1, wherein the antigen binding molecule or an affinity matured mutant specifically binds to membrane-bound human LIGHT.

### Claim 3 (depends on 1)

The anti-LIGHT antigen binding molecule or an affinity matured mutant of claim 1, wherein the antigen binding molecule or an affinity matured mutant has from about 10 times to about 100 times higher affinity for membrane bound LIGHT compared to soluble LIGHT.

### Claim 4

An anti-LIGHT antigen binding molecule comprising:
a VHCDR3 having at least 80% identity to the amino acid sequence of any one of SEQ ID NOs 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104, 112 and 120; and/or
a VLCDR3 having at least 80% identity to the amino acid sequence of any one of SEQ ID NOs 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, and 116.

### Claim 5 (depends on 4)

The anti-LIGHT antigen binding molecule of claim 4 comprising:
a VHCDR3 having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104, 112 and 120; and/or
a VLCDR3 having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, and 116.

### Claim 6 (depends on 1)

The anti-LIGHT antigen binding molecule of claim 1 wherein the anti-LIGHT antigen binding molecule is an antibody selected from the group consisting of 2E08, 3A07, 3B04, 3C10, 3D12, 3E09, 2B11, 3B04_var1, 3B04_var2, 3B04_var3, 3B04_var4, 3B04_var5, 3B04_var6, 3B04_var7, 3B04_var8, 3B04_var9, 3B04_var10, 3B04_var11, 3B04_var12, 3B04_var13, 3B04_var14, 3B04_var15, 3B04_var16, 3D12_var1, 3D12_var2, 3D12_var3, 3D12_var4, 3D12_var5, 3D12_var6, 3D12_var7, 3D12_var8, 3D12_var9, 3D12_var10, 3D12_var11, 3D12_var12, 3D12_var13, 3D12_var14, 3D12_var15 and 3D12_var16.

### Claim 7 (depends on 6)

An affinity matured mutant antibody derived from the antigen binding molecule of claim 6.

### Claim 8 (depends on 1)

The anti-LIGHT antigen binding molecule or affinity matured mutant of claim 1 comprising:
a heavy chain variable region having at least 80% identity to the amino acid sequence selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 21, SEQ ID NO: 29, SEQ ID NO: 37, SEQ ID NO: 45, SEQ ID NO: 53, SEQ ID NO: 61, SEQ ID NO: 69, SEQ ID NO: 77, SEQ ID NO: 85, SEQ ID NO: 93, SEQ ID NO: 101, SEQ ID NO: 109, SEQ ID NO: 117;
and/or
a light chain variable region having at least 80% identity to the amino acid sequence selected from the group consisting of consisting SEQ ID NO: 1, SEQ ID NO: 9, SEQ ID NO: 17, SEQ ID NO: 25, SEQ ID NO: 33, SEQ ID NO: 41, SEQ ID NO: 49, SEQ ID NO: 57, SEQ ID NO: 65, SEQ ID NO: 73, SEQ ID NO: 81, SEQ ID NO: 89, SEQ ID NO: 97, SEQ ID NO: 105, SEQ ID NO: 113.

### Claim 9 (depends on 8)

The anti-LIGHT antigen binding or affinity matured mutant molecule of claim 8 comprising:
a heavy chain variable region having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 21, SEQ ID NO: 29, SEQ ID NO: 37, SEQ ID NO: 45, SEQ ID NO: 53, SEQ ID NO: 61, SEQ ID NO: 69, SEQ ID NO: 77, SEQ ID NO: 85, SEQ ID NO: 93, SEQ ID NO: 101, SEQ ID NO: 109, SEQ ID NO: 117;
and/or
a light chain variable region having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence selected from the group consisting of consisting SEQ ID NO: 1, SEQ ID NO: 9, SEQ ID NO: 17, SEQ ID NO: 25, SEQ ID NO: 33, SEQ ID NO: 41, SEQ ID NO: 49, SEQ ID NO: 57, SEQ ID NO: 65, SEQ ID NO: 73, SEQ ID NO: 81, SEQ ID NO: 89, SEQ ID NO: 97, SEQ ID NO: 105, SEQ ID NO: 113.

### Claim 10 (depends on 1)

The anti-LIGHT antigen binding molecule or affinity matured mutant of claim 1, wherein the antigen binding molecule or affinity matured mutant comprises:
a VHCDR1 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of any one of SEQ ID NOs 38, 125, 6, 46, 127, 14, 22, 30, 54, 62, 70, 78, 86, 94, 102, 110, 118;
a VHCDR2 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of any one of SEQ ID NOs 39, 126, 7, 47, 128, 15, 23, 31, 55, 63, 71, 79, 87, 95, 103, 111, 119; and
a VHCDR3 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of any one of SEQ ID NOs 40, 8, 48, 16, 24, 32, 56, 64, 72, 80, 88, 96, 104, 112 and 120;
and/or
a VLCDR1 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of any one of SEQ ID NOs 34, 2, 42, 10, 18, 26, 50, 58, 66, 74, 82, 90, 98, 106, 114;
a VLCDR2 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of any one of SEQ ID NOs; 35, 3, 43, 11, 19, 27, 51, 59, 67, 75, 83, 91, 99, 107, 115; and
a VLCDR3 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of any one of SEQ ID NOs 36, 4, 44, 12, 20, 28, 52, 60, 68, 76, 84, 92, 100, 108, and 116.

### Claim 11 (depends on 1)

The anti-LIGHT antigen binding molecule or affinity matured mutant of claim 1, wherein the antigen binding molecule or affinity matured mutant is selected from the group consisting of:
(a) an anti-LIGHT antigen binding molecule comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 38), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYSQKFQG (SEQ ID NO: 39) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 40); and
a light chain variable region comprising a VLCDR1 comprising the amino acid sequence RASENIYGALN (SEQ ID NO: 34), a VLCDR2 comprising the amino acid sequence GATNLAE (SEQ ID NO: 35) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 36);
(b) an anti-LIGHT antigen binding molecule comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 6), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYSQKFKG (SEQ ID NO: 7), a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 8); and
a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 2), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 3) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 4);
(c) an anti-LIGHT antigen binding molecule comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 46), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYNQKFKG (SEQ ID NO: 47), a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 48); and
a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 44);
(d) an anti-LIGHT antigen binding molecule comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYAIH (SEQ ID NO: 86), a VHCDR2 comprising the amino acid sequence VISTYYGDASYNQKFKG (SEQ ID NO: 87), a VHCDR3 comprising the amino acid SRGEYGNYDAMDY sequence (SEQ ID NO: 88); and
a light chain variable region comprising a VLCDR1 comprising the amino acid sequence KASQSVDYDGDSYMN (SEQ ID NO: 82), a VLCDR2 comprising the amino acid sequence AASNLES (SEQ ID NO: 83) and a VLCDR3 comprising the amino acid sequence QQSNEDPLT (SEQ ID NO: 84);
(e) an anti-LIGHT antigen binding molecule comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 94), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYNQKFKG (SEQ ID NO: 95), a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 96); and
a light chain variable region comprising a VLCDR1 comprising the amino acid sequence SASSSVSYMY (SEQ ID NO: 90), a VLCDR2 comprising the amino acid sequence DTSNLAS (SEQ ID NO: 91) and a VLCDR3 comprising the amino acid sequence QQWSSYPLT (SEQ ID NO: 92);
(f) an anti-LIGHT antigen binding molecule comprising heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 102), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYNQKFKG (SEQ ID NO: 103), a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 104); and
a light chain variable region comprising a VLCDR1 comprising the amino acid sequence SASSSVSYMY (SEQ ID NO: 98), a VLCDR2 comprising the amino acid sequence DTSNLAS (SEQ ID NO: 99) and a VLCDR3 comprising the amino acid sequence QQWSSYPLT (SEQ ID NO: 100);
(g) an anti-LIGHT antigen binding molecule comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYYMY (SEQ ID NO: 110), a VHCDR2 comprising the amino acid sequence AIGDGGIYTYYADTVKG (SEQ ID NO: 111), a VHCDR3 comprising the amino acid sequence GTGDGFAY (SEQ ID NO: 112); and
a light chain variable region comprising a VLCDR1 comprising the amino acid sequence RASESVDSYGNSFMH (SEQ ID NO: 106), a VLCDR2 comprising the amino acid sequence LASNLES (SEQ ID NO: 107) and a VLCDR3 comprising the amino acid sequence QQNNEDPYT (SEQ ID NO: 108);
(h) an anti-LIGHT antigen binding molecule comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYAIH (SEQ ID NO: 118), a VHCDR2 comprising the amino acid sequence VISTYYGDASYNQKFKG (SEQ ID NO: 119), a VHCDR3 comprising the amino acid sequence SRGEYGNYDAMDY (SEQ ID NO: 120); and
a light chain variable region comprising a VLCDR1 comprising the amino acid sequence RASESVDSYGNSFMH (SEQ ID NO: 114), a VLCDR2 comprising the amino acid sequence RASNLES (SEQ ID NO: 115) and a VLCDR3 comprising the amino acid sequence QQSNEDPYT (SEQ ID NO: 116);
(i) an anti-LIGHT antigen binding molecule comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence GYTFTDY (SEQ ID NO: 125), a VHCDR2 comprising the amino acid sequence DPETGDTA (SEQ ID NO: 126), a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 8); and
a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 2), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 3) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 4); and
(j) an anti-LIGHT antigen binding molecule comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYTFTDS (SEQ ID NO: 127), a VHCDR2 comprising the amino acid sequence DPETGGTA (SEQ ID NO: 128), a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 48); and
a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 44).

### Claim 12

An antigen-binding molecule that specifically binds to an epitope of human LIGHT wherein the epitope comprises the amino acids GRATSSSRVW (SEQ ID NO: 124).

### Claim 13 (depends on 1)

A nucleic acid encoding the antigen binding molecule or affinity matured mutant of claim 1.

### Claim 14 (depends on 13)

A plasmid comprising the nucleic acid of claim 13.

### Claim 15 (depends on 13)

A vector comprising the nucleic acid of claim 13.

### Claim 16 (depends on 1)

A pharmaceutical composition comprising an antigen binding molecule of claim 1 and a pharmaceutically acceptable excipient.

### Claim 17 (depends on 1)

A method of treating or preventing a LIGHT-mediated disease or disorder comprising administering to a patient an antigen binding molecule or affinity matured mutant of claim 1.

### Claim 18 (depends on 1)

A method of treating or preventing an inflammatory disorder or disease or an autoimmune disorder or disease comprising administering to a patient an antigen binding molecule or affinity matured mutant of claim 1.

### Claim 19 (depends on 1)

A method of inhibiting interferon-gamma release by administering to a patient an antigen binding molecule or affinity matured mutant of claim 1.

### Claim 20 (depends on 17)

The method of claim 17, wherein the antigen binding molecule or affinity matured mutant is 3B04, 3D12 or variants thereof.