Monoclonal Antibody

• US 20110070613A1
• Filed: 02/05/2010
• Published: 03/24/2011
• Est. Priority Date: 12/12/2005
• Status: Abandoned Application

• Current Assignee: AC Immune SA
• Original Assignee: AC Immune SA
• Inventors: NICOLAU, CLAUDE, HICKMAN, DAVID, GREFERATH, RUTH, PFEIFER, ANDREA, MUHS, ANDREAS
• Application Number:
  US12/701,199
• Publication Number:
  US 20110070613A1
• Time in Patent Office: Days
• US Class Current: 435/69.6
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: 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
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: G01N 2333/4709 Amyloid plaque core protein

Abstract

The present invention is related to methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer'"'"'s disease. The present invention provides novel methods and compositions comprising highly specific and highly effective antibodies having the ability to specifically recognize and bind to specific epitopes from a range of β-amyloid proteins. The antibodies enabled by the teaching of the present invention are particularly useful for the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis including, but not limited to, neurological disorders such as Alzheimer'"'"'s Disease (AD).

Claims

1-169. -169. (canceled)

170. A nucleic acid molecule comprising a nucleotide sequence encoding the heavy chain or the light chain of a monoclonal antibody that binds to at least two sites on β

-amyloid proteins, amyloid β

fibers, amyloid β

monomers or amyloid β

oligomers, wherein said at least two sites are selected from the group consisting of

(i) one H is residue within SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

16, SEQ ID NO;

18, or SEQ ID NO;

20;

(ii) -Phe-Phe- within SEQ ID NO;

14, SEQ ID NO;

15, SEQ ID NO;

16, SEQ ID NO;

17, SEQ ID NO;

18, SEQ ID NO;

19 or SEQ ID NO;

20, wherein said antibody or functional fragment thereof predominantly binds to said -Phe-Phe-; and

(iii) -Lys-Leu- within SEQ ID NO;

13, SEQ ID NO;

15, SEQ ID NO;

16, SEQ ID NO;

17, SEQ ID NO;

18, or SEQ ID NO;

20, wherein said antibody or functional fragment thereof predominantly binds to said -Lys-Leu-.

173. The nucleic acid of claim 170 encoding the monoclonal antibody produced by the hybridoma cell line FP 12H3, deposited as DSM ACC2752.

174. The nucleic acid of claim 170 encoding the monoclonal antibody produced by the hybridoma cell line FP 12H3-C2, deposited as DSM ACC2750.

175. The nucleic acid of claim 170 encoding the monoclonal antibody produced by the hybridoma cell line FP 12H3-G2, deposited as DSM ACC2751.

176. The nucleic acid of claim 170 encoding the monoclonal antibody produced by the hybridoma cell line ET 7E3, deposited as DSM ACC2755.

177. The nucleic acid of claim 170 encoding the monoclonal antibody produced by the hybridoma cell line EJ 7H3, deposited as DSM ACC2756.

182. A host cell comprising the nucleic acid molecule of any one of claims 170 to 181.

183. The host cell of claim 182, wherein the host cell is a bacterial cell, insect cell or mammalian cell.

184. A method for producing a monoclonal antibody, which specifically binds to monomeric, oligomeric or polymeric forms of amyloid-0, comprising culturing the host cell of claim 182.

171. A nucleic acid molecule comprising a nucleotide sequence encoding the light chain of a monoclonal antibody, which specifically binds to monomeric, oligomeric or polymeric forms of amyloid-β

, wherein;

(i) the CDR1 of the light chain variable region of the monoclonal antibody has the amino acid sequence of SEQ ID NO;

23;

(ii) the CDR2 of the light chain variable region of the monoclonal antibody has the amino acid sequence of SEQ ID NO;

24; and

(iii) the CDR3 of the light chain variable region of the monoclonal antibody has the amino acid sequence of SEQ ID NO;

25.

178. The nucleic acid molecule of claim 171 wherein the nucleotide sequence encodes the light chain variable region of SEQ ID NO:

7.

179. The nucleic acid molecule of claim 171, wherein the nucleotide sequence is SEQ ID NO:

9 or the complementary sequence of SEQ ID NO;

9.

172. A nucleic acid molecule comprising a nucleotide sequence encoding the heavy chain of a monoclonal antibody, which specifically binds to monomeric, oligomeric or polymeric forms of amyloid-β

, wherein;

(i) the CDR1 of the heavy chain variable region of the monoclonal antibody has the amino acid sequence of SEQ ID NO;

26;

(ii) the CDR2 of the heavy chain variable region of the monoclonal antibody has the amino acid sequence of SEQ ID NO;

27; and

(iii) the CDR3 of the heavy chain variable region of the monoclonal antibody has the amino acid sequence of SEQ ID NO;

28.

180. The nucleic acid molecule of claim 172 wherein the nucleotide sequence encodes the heavy chain variable region of SEQ ID NO:

8.

181. The nucleic acid molecule of claim 172, wherein the nucleotide sequence is SEQ ID NO:

11 or the complementary sequence of SEQ ID NO;

11.