US 10,870,709 B2Granted

Specific murine and humanized monoclonal antibodies detecting pathology associated secondary structure changes in proteins and peptides

AssigneeNew York University

InventorsThomas M. Wisniewski, Fernando Goni

Life of this patent

Estimating the term…

Abstract

The present invention relates to antibodies and binding fragments thereof that bind the β-sheet secondary structure of a pathological monomeric or oligomeric non-fibrillar proteins without binding to the non-toxic, non-pathological forms of these proteins or peptides These antibodies and binding fragments thereof are suitable for the diagnosis, prevention, and treatment of protein conformational disorders including all amyloid diseases.

Claims19

Dependent claims

An antibody or binding fragment thereof that binds β-sheet secondary structure of pathologic monomeric or oligomeric non-fibrillar proteins/peptides, said antibody or binding fragment thereof comprising:

(a) a heavy chain variable region, wherein said heavy chain variable region comprises a complementarity-determining region 1 (H-CDR1) comprising the amino acid sequence of SEQ ID NO:
23, a complementarity-determining region 2 (H-CDR2) comprising the amino acid sequence of SEQ ID NO:
27, and a complementarity-determining region 3 (H-CDR3) comprising the amino acid sequence of SEQ ID NO:
31;
and a light chain variable region, wherein said light chain variable region comprises a complementarity-determining region 1 (L-CDR1) comprising the amino acid sequence of SEQ ID NO:
35, a complementarity-determining region 2 (L-CDR2) comprising the amino acid sequence of SEQ ID NO:
40, and a complementarity-determining region 3 (L-CDR3) comprising the amino acid sequence of SEQ ID NO:
45;
(b) a heavy chain variable region, wherein said heavy chain variable region comprises a H-CDR1 comprising the amino acid sequence of SEQ ID NO:
24, a H-CDR2 comprising the amino acid sequence of SEQ ID NO:
28, and a H-CDR3 comprising the amino acid sequence of SEQ ID NO:
32;
and a light chain variable region, wherein said light chain variable region comprises a L-CDR1 comprising the amino acid sequence of SEQ ID NO:
36, a L-CDR2 comprising the amino acid sequence of SEQ ID NO:
41, and a L-CDR3 comprising the amino acid sequence of SEQ ID NO:
46;
(c) a heavy chain variable region, wherein said heavy chain variable region comprises a H-CDR1 comprising the amino acid sequence of SEQ ID NO:
25, a H-CDR2 comprising the amino acid sequence of SEQ ID NO:
29, and a H-CDR3 comprising the amino acid sequence of SEQ ID NO:
33;
and a light chain variable region, wherein said light chain variable region comprises a L-CDR1 comprising the amino acid sequence of SEQ ID NO:
37, a L-CDR2 comprising the amino acid sequence of SEQ ID NO:
42, and a L-CDR3 comprising the amino acid sequence of SEQ ID NO:
47;
(d) a heavy chain variable region, wherein said heavy chain variable region comprises a H-CDR1 comprising the amino acid sequence of SEQ ID NO:
26, a H-CDR2 comprising the amino acid sequence of SEQ ID NO:
30, and a H-CDR3 comprising the amino acid sequence of SEQ ID NO:
34;
and a light chain variable region, wherein said light chain variable region comprises a L-CDR1 comprising the amino acid sequence of SEQ ID NO:
39, a L-CDR2 comprising the amino acid sequence of SEQ ID NO:
44, and a L-CDR3 comprising the amino acid sequence of SEQ ID NO:
49;
(e) a heavy chain variable region, wherein said heavy chain variable region comprises a H-CDR1 comprising the amino acid sequence of SEQ ID NO:
50, a H-CDR2 comprising the amino acid sequence of SEQ ID NO:
51, and a H-CDR3 comprising the amino acid sequence of SEQ ID NO:
52;
and a light chain variable region, wherein said light chain variable region comprises a L-CDR1 comprising the amino acid sequence of SEQ ID NO:
53, a L-CDR2 comprising the amino acid sequence of SEQ ID NO:
54, and a L-CDR3 comprising the amino acid sequence of SEQ ID NO:
55;
(f) a heavy chain variable region comprising the H-CDR1 comprises the amino acid sequence of SEQ ID NO:
23, the H-CDR2 comprising the amino acid sequence of SEQ ID NO:
27, and the H-CDR3 comprising the amino acid sequence of SEQ ID NO:
31;
a light chain variable region, wherein said light chain variable region comprises a L-CDR1 comprising the amino acid sequence of SEQ ID NO:
38, a L-CDR2 comprising the amino acid sequence of SEQ ID NO:
43, and a L-CDR3 comprising the amino acid sequence of SEQ ID NO:
48;
and
(g) a heavy chain variable region, wherein said heavy chain variable region comprises a H-CDR1 comprising the amino acid sequence of SEQ ID NO:
50, a H-CDR2 comprising the amino acid sequence of SEQ ID NO:
51, and a H-CDR3 comprising the amino acid sequence of SEQ ID NO:
52;
and a light chain variable region, wherein said light chain variable region comprises a L-CDR1 comprising the amino acid sequence of SEQ ID NO:
53, a L-CDR2 comprising the amino acid sequence of SEQ ID NO:
112, and a L-CDR3 comprising the amino acid sequence of SEQ ID NO:
55.

54 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/319,682Filed 22 Jul 2017 · us provisional application
Priority: 22 Jul 2016
Published: US 2019/0256612 A122 Aug 2019
Granted: 22 Dec 2020
Term ends: Not estimatedThe source records don’t support an estimate.

Classification12 codes

C07K 16/44
Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies: against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA,…
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…
C07K 7/06
Linear peptides containing only normal peptide links: having 5 to 11 amino acids
C07K 14/00
Peptides having more than 20 amino acids

Family

Application62/365,465Us provisional application · filed 22 Jul 2016
US 2019/0256612 A1Pre-grant publication · published 22 Aug 2019
US 10,870,709 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

(a) a heavy chain variable region, wherein said heavy chain variable region comprises a complementarity-determining region 1 (H-CDR1) comprising the amino acid sequence of SEQ ID NO:
23, a complementarity-determining region 2 (H-CDR2) comprising the amino acid sequence of SEQ ID NO:
27, and a complementarity-determining region 3 (H-CDR3) comprising the amino acid sequence of SEQ ID NO:
31;
and a light chain variable region, wherein said light chain variable region comprises a complementarity-determining region 1 (L-CDR1) comprising the amino acid sequence of SEQ ID NO:
35, a complementarity-determining region 2 (L-CDR2) comprising the amino acid sequence of SEQ ID NO:
40, and a complementarity-determining region 3 (L-CDR3) comprising the amino acid sequence of SEQ ID NO:
45;
(b) a heavy chain variable region, wherein said heavy chain variable region comprises a H-CDR1 comprising the amino acid sequence of SEQ ID NO:
24, a H-CDR2 comprising the amino acid sequence of SEQ ID NO:
28, and a H-CDR3 comprising the amino acid sequence of SEQ ID NO:
32;
and a light chain variable region, wherein said light chain variable region comprises a L-CDR1 comprising the amino acid sequence of SEQ ID NO:
36, a L-CDR2 comprising the amino acid sequence of SEQ ID NO:
41, and a L-CDR3 comprising the amino acid sequence of SEQ ID NO:
46;
(c) a heavy chain variable region, wherein said heavy chain variable region comprises a H-CDR1 comprising the amino acid sequence of SEQ ID NO:
25, a H-CDR2 comprising the amino acid sequence of SEQ ID NO:
29, and a H-CDR3 comprising the amino acid sequence of SEQ ID NO:
33;
and a light chain variable region, wherein said light chain variable region comprises a L-CDR1 comprising the amino acid sequence of SEQ ID NO:
37, a L-CDR2 comprising the amino acid sequence of SEQ ID NO:
42, and a L-CDR3 comprising the amino acid sequence of SEQ ID NO:
47;
(d) a heavy chain variable region, wherein said heavy chain variable region comprises a H-CDR1 comprising the amino acid sequence of SEQ ID NO:
26, a H-CDR2 comprising the amino acid sequence of SEQ ID NO:
30, and a H-CDR3 comprising the amino acid sequence of SEQ ID NO:
34;
and a light chain variable region, wherein said light chain variable region comprises a L-CDR1 comprising the amino acid sequence of SEQ ID NO:
39, a L-CDR2 comprising the amino acid sequence of SEQ ID NO:
44, and a L-CDR3 comprising the amino acid sequence of SEQ ID NO:
49;
(e) a heavy chain variable region, wherein said heavy chain variable region comprises a H-CDR1 comprising the amino acid sequence of SEQ ID NO:
50, a H-CDR2 comprising the amino acid sequence of SEQ ID NO:
51, and a H-CDR3 comprising the amino acid sequence of SEQ ID NO:
52;
and a light chain variable region, wherein said light chain variable region comprises a L-CDR1 comprising the amino acid sequence of SEQ ID NO:
53, a L-CDR2 comprising the amino acid sequence of SEQ ID NO:
54, and a L-CDR3 comprising the amino acid sequence of SEQ ID NO:
55;
(f) a heavy chain variable region comprising the H-CDR1 comprises the amino acid sequence of SEQ ID NO:
23, the H-CDR2 comprising the amino acid sequence of SEQ ID NO:
27, and the H-CDR3 comprising the amino acid sequence of SEQ ID NO:
31;
a light chain variable region, wherein said light chain variable region comprises a L-CDR1 comprising the amino acid sequence of SEQ ID NO:
38, a L-CDR2 comprising the amino acid sequence of SEQ ID NO:
43, and a L-CDR3 comprising the amino acid sequence of SEQ ID NO:
48;
and
(g) a heavy chain variable region, wherein said heavy chain variable region comprises a H-CDR1 comprising the amino acid sequence of SEQ ID NO:
50, a H-CDR2 comprising the amino acid sequence of SEQ ID NO:
51, and a H-CDR3 comprising the amino acid sequence of SEQ ID NO:
52;
and a light chain variable region, wherein said light chain variable region comprises a L-CDR1 comprising the amino acid sequence of SEQ ID NO:
53, a L-CDR2 comprising the amino acid sequence of SEQ ID NO:
112, and a L-CDR3 comprising the amino acid sequence of SEQ ID NO:
55.

54 more elements

Facts

Application

16/319,682Filed 22 Jul 2017 · us provisional application

Priority

22 Jul 2016

Published

US 2019/0256612 A122 Aug 2019

Granted

22 Dec 2020

Term ends

Not estimatedThe source records don’t support an estimate.

Classification12 codes

C07K 16/44
Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies: against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA,…
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…
C07K 7/06
Linear peptides containing only normal peptide links: having 5 to 11 amino acids
C07K 14/00
Peptides having more than 20 amino acids