Human anti-SOD1 antibodies

Patent metadata

Field	Value
Publication number	US-9283271-B2
Application number	US-201113992840-A
Country	US
Kind code	B2
Filing date	Dec 19, 2011
Priority date	Dec 17, 2010
Publication date	Mar 15, 2016
Grant date	Mar 15, 2016

Abstract

Provided are novel human copper-zinc superoxide dismutase, also known as superoxide dismutase 1 or SOD1, specific antibodies as well as fragments, derivatives and variants thereof as well as methods related thereto. Assays, kits, and solid supports related to antibodies specific for SOD1 are also disclosed. The antibody, immunoglobulin chain(s), as well as binding fragments, derivatives and variants thereof can be used in pharmaceutical and diagnostic compositions for SOD1 targeted immunotherapy and diagnosis, respectively.

First claim

The invention claimed is:

1. A cDNA molecule encoding a human anti-SOD1 antibody or an antigen-binding fragment thereof capable of binding to misfolded or aggregated SOD1; wherein the encoded antibody or antigen-binding fragment thereof comprises in its variable region the complementarity determining regions (CDRs) depicted in any one of FIGS. 1A-1L , and wherein the encoded antibody
(i) binds to physiological SOD1 dimers
(ii) preferentially recognizes the misfolded or aggregated SOD1 over physiological SOD1 dimers, or
(iii) does not substantially recognize physiological SOD1 dimers.

2. The cDNA of claim 1 , wherein the antibody or antigen binding fragment thereof selectively binds to human wildtype and murine SOD1.

3. The cDNA of claim 1 , wherein the antibody or antigen binding fragment thereof which binds to physiological SOD1, specifically binds an SOD1 epitope comprising or consisting of an amino acid sequence selected from the group consisting of:

(SEQ ID NO: 51)

GGPKDEERHVG,

(SEQ ID NO: 53)

IIGRTLV,

or

(SEQ ID NO: 55)

HEKADDLGKGGNEES.

4. The cDNA of claim 1 , wherein the antibody or antigen binding fragment thereof which preferentially recognizes misfolded or aggregated SOD1 over physiological SOD1 dimers, or which does not substantially recognize physiological SOD1 dimers, specifically binds an SOD1 epitope comprising or consisting of an amino acid sequence selected from the group consisting of:

(SEQ ID NO: 2)

DGVADVS,

(SEQ ID NO: 51)

GGPKDEERHVG,

(SEQ ID NO: 53)

IIGRTLV,

(SEQ ID NO: 54)

LGNVTADKDGV,

(SEQ ID NO: 55)

HEKADDLGKGGNEES,

(SEQ ID NO: 56)

EDSVISL,

(SEQ ID NO: 57)

KTGNAGS,

(SEQ ID NO: 58)

LGNVTADKDGV,

or

(SEQ ill NO: 59)

GGPKDEE.

5. The cDNA of claim 1 , which is derived from mRNA obtained from a human memory B-cell.

6. The cDNA of claim 5 , wherein the antibody or antigen binding fragment thereof further comprises a polypeptide sequence which is heterologous to at least one CDR.

7. The cDNA of claim 6 , wherein the human constant domain is of the IgG-type.

8. The cDNA of claim 5 , wherein the antibody or antigen-binding fragment thereof comprises in its variable region a set of complementarity determining regions (CDRs) selected from:
(i) VHCDR1: positions 31-35 of SEQ ID NO:60,
VHCDR2: positions 50-66 of SEQ ID NO:60,
VHCDR3: positions 99-115 of SEQ ID NO:60,
VKCDR1: positions 24-38 of SEQ ID NO:61,
VKCDR2: positions 54-60 of SEQ ID NO:61,
VKCDR3: positions 93-101 of SEQ ID NO:61;
(ii) VHCDRI: positions 31-35 of SEQ ID NO:62,
VHCDR2: positions 50-66 of SEQ ID NO:62,
VHCDR3: positions 109-132 of SEQ ID NO:62
VLCDRI: positions 23-33 of SEQ ID NO:63,
VLCDR2: positions 49-55 of SEQ ID NO:63,
VLCDR3: LSADSSGTWV positions 89-98 of SEQ ID NO:63;
(iii) VHCDRI: positions 31-35 of SEQ ID NO:64,
VHCDR2: positions 50-66 of SEQ ID NO:64,
VHCDR3: positions 99-110 of SEQ ID NO:64,
VKCDR1: positions 24-34 of SEQ ID NO:65,
VKCDR2: positions 50-56 of SEQ ID NO:65,
VKCDR3: positions 89-97 of SEQ ID NO:65;
(iv) VHCDRI: positions 31-35 of SEQ ID NO:66,
VHCDR2: positions 50-66 of SEQ ID NO:66,
VHCDR3: positions 100-115 of SEQ ID NO:66,
VLCDRI: positions 22-33 of SEQ ID NO:67,
VLCDR2: positions 49-55 of SEQ ID NO:67,
VLCDR3: positions 89-99 of SEQ ID NO:67;
(v) VHCDRI: positions 31-35 of SEQ ID NO:68,
VHCDR2: positions 50-66 of SEQ ID NO:68,
VHCDR3: positions 102-117 of SEQ ID NO:68,
VLCDR1: positions 24-33 of SEQ ID NO:69,
VLCDR2: positions 50-56 of SEQ ID NO:69,
VLCDR3: positions 90-98 of SEQ ID NO:69;
(vi) VHCDRI: positions 31-35 of SEQ ID NO:70,
VHCDR2: positions 50-66 of SEQ ID NO:70,
VHCDR3: positions 100-114 of SEQ ID NO:70,
VLCDR1: positions 24-34 of SEQ ID NO:71,
VLCDR2: positions 50-56 of SEQ ID NO:71,
VLCDR3: positions 90-98 of SEQ ID NO:71;
(vii) VHCDRI: positions 31-35 of SEQ ID NO:72,
VHCDR2: positions 50-60 of SEQ ID NO:72,
VHCDR3: positions 98-111 of SEQ ID NO:72,
VLCDRI: positions 23-33 of SEQ ID NO:73,
VLCDR2: positions 49-55 of SEQ ID NO:73,
VLCDR3: positions 88-98 of SEQ ID NO:73;
(viii) VHCDRI: positions 31-35 of SEQ ID NO:74,
VHCDR2: positions 50-66 of SEQ ID NO:74,
VHCDR3: positions 99-110 of SEQ ID NO:74,
VLCDRI: positions 23-33 of SEQ ID NO:75,
VLCDR2: positions 49-55 of SEQ ID NO:75,
VLCDR3: positions 88-97 of SEQ ID NO:75;
(ix) VHCDRI: positions 31-35 of SEQ ID NO:76,
VHCDR2: positions 50-66 of SEQ ID NO:76,
VHCDR3: positions 99-119 of SEQ ID NO:76
VLCDR1: positions 23-33 of SEQ ID NO:77,
VLCDR2: positions 49-55 of SEQ ID NO:77,
VLCDR3: positions 88-98 of SEQ ID NO:77;
(x) VHCDRI: positions 31-35 of SEQ ID NO:78,
VHCDR2: positions 50-66 of SEQ ID NO:78,
VHCDR3: positions 99-103 of SEQ ID NO:78,
VLCDRI: positions 23-33 of SEQ ID NO:79,
VLCDR2: positions 49-55 of SEQ ID NO:79,
VLCDR3: positions 88-97 of SEQ ID NO:79;
(xi) VHCDRI: positions 31-35 of SEQ ID NO:80,
VHCDR2: positions 50-68 of SEQ ID NO:80,
VHCDR3: positions 101-111 of SEQ ID NO:80,
VLCDR1: positions 23-33 of SEQ ID NO:81,
VLCDR2: positions 49-55 of SEQ ID NO:81,
VLCDR3: positions 88-98 of SEQ ID NO:81; or
(xii) VHCDRI: positions 31-35 of SEQ ID NO:82,
VHCDR2: positions 49-65 of SEQ ID NO:82,
VHCDR3: positions 98-108 of SEQ ID NO:82,
VLCDR1: positions 23-35 of SEQ ID NO:83,
VLCDR2: positions 51-57 of SEQ ID NO:83,
VLCDR3: positions 90-100 of SEQ ID NO:83.

9. The cDNA of claim 1 , wherein the antibody is selected from the group consisting of a chimeric murine-human or a murinized antibody.

Assignees

• Montrasio Fabio
• Barenco Montrasio Maria Grazia
• Grimm Jan
• Nitsch Roger
• Hock Christoph
• Maier Marcel
• Neurimmune Holding Ag
• Univ Zuerich

Inventors

• Montrasio Fabio
• Barenco Montrasio Maria Grazia
• Grimm Jan
• Nitsch Roger
• Hock Christoph
• Maier Marcel

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P21/02

  Muscle relaxants, e.g. for tetanus or cramps · CPC title

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• C12Y115/01001

  Superoxide dismutase (1.15.1.1) · CPC title

• C07K2317/30

  characterized by aspects of specificity or valency · CPC title