Novel nicotine-binding antibodies

Abstract

Described are novel nicotine-binding antibodies and methods of using them for treating nicotine addiction and/or facilitating smoking cessation, or for treating nicotine overdose or nicotine poisoning.

1 . A nicotine-binding antibody or nicotine-binding fragment thereof, comprising a heavy chain sequence and a light chain sequence selected from:
 a. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 1 and a light chain sequence with at least about 95% identity to of SEQ ID NO: 2;   b. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 3 and a light chain sequence with at least about 95% identity to SEQ ID NO: 4;   c. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 5 and a light chain sequence with at least about 95% identity to SEQ ID NO: 6;   d. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 7 and a light chain sequence with at least about 95% identity to SEQ ID NO: 8;   e. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 9 and a light chain sequence with at least about 95% identity to SEQ ID NO: 10;   f. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 11 and a light chain sequence with at least about 95% identity to SEQ ID NO: 12;   g. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 13 and a light chain sequence with at least about 95% identity to SEQ ID NO: 14;   h. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 15 and a light chain sequence with at least about 95% identity to SEQ ID NO: 16;   i. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 17 and a light chain sequence with at least about 95% identity to SEQ ID NO: 18;   j. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 19 and a light chain sequence with at least about 95% identity to SEQ ID NO: 20   k. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 21 and a light chain sequence with at least about 95% identity to of SEQ ID NO: 22;   l. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 23 and a light chain sequence with at least about 95% identity to SEQ ID NO: 24;   m. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 25 and a light chain sequence with at least about 95% identity to SEQ ID NO: 26;   n. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 27 and a light chain sequence with at least about 95% identity to SEQ ID NO: 28;   o. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 29 and a light chain sequence with at least about 95% identity to SEQ ID NO: 30;   p. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 31 and a light chain sequence with at least about 95% identity to SEQ ID NO: 32;   q. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 33 and a light chain sequence with at least about 95% identity to SEQ ID NO: 34;   r. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 35 and a light chain sequence with at least about 95% identity to SEQ ID NO: 36;   s. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 37 and a light chain sequence with at least about 95% identity to SEQ ID NO: 38; and   t. a heavy chain sequence with at least about 95% identity to SEQ ID NO: 39 and a light chain sequence with at least about 95% identity to SEQ ID NO: 40.   
     
     
         2 . The nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 1 , wherein:
 a. the heavy chain sequence has at least about 98% identity to SEQ ID NO: 1 and the light chain sequence has at least about 98% identity to SEQ ID NO: 2;   b. the heavy chain sequence has at least about 98% identity to SEQ ID NO: 3 and the light chain sequence has at least about 98% identity to SEQ ID NO: 4;   c. the heavy chain sequence has at least about 98% identity to SEQ ID NO: 5 and the light chain sequence has at least about 98% identity to SEQ ID NO: 6;   d. the heavy chain sequence has at least about 98% identity to SEQ ID NO: 7 and the light chain sequence has at least about 98% identity to SEQ ID NO: 8;   e. the heavy chain sequence has at least about 98% identity to SEQ ID NO: 9 and the light chain sequence has at least about 98% identity to SEQ ID NO: 10;   f. the heavy chain sequence has at least about 98% identity to SEQ ID NO: 11 and the light chain sequence has at least about 98% identity to SEQ ID NO: 12;   g. the heavy chain sequence has at least about 98% identity to SEQ ID NO: 13 and the light chain sequence has at least about 98% identity to SEQ ID NO: 14;   h. the heavy chain sequence has at least about 98% identity to SEQ ID NO: 15 and the light chain sequence has at least about 98% identity to SEQ ID NO: 16;   i. the heavy chain sequence has at least about 98% identity to SEQ ID NO: 17 and the light chain sequence has at least about 98% identity to SEQ ID NO: 18;   j. the heavy chain sequence has at least about 98% identity to SEQ ID NO: 19 and the light chain sequence has at least about 98% identity to SEQ ID NO: 20;   k. a heavy chain sequence with at least about 98% identity to SEQ ID NO: 21 and a light chain sequence with at least about 98% identity to of SEQ ID NO: 22;   l. a heavy chain sequence with at least about 98% identity to SEQ ID NO: 23 and a light chain sequence with at least about 98% identity to SEQ ID NO: 24;   m. a heavy chain sequence with at least about 98% identity to SEQ ID NO: 25 and a light chain sequence with at least about 98% identity to SEQ ID NO: 26;   n. a heavy chain sequence with at least about 98% identity to SEQ ID NO: 27 and a light chain sequence with at least about 98% identity to SEQ ID NO: 28;   o. a heavy chain sequence with at least about 98% identity to SEQ ID NO: 29 and a light chain sequence with at least about 98% identity to SEQ ID NO: 30;   p. a heavy chain sequence with at least about 98% identity to SEQ ID NO: 31 and a light chain sequence with at least about 98% identity to SEQ ID NO: 32;   q. a heavy chain sequence with at least about 98% identity to SEQ ID NO: 33 and a light chain sequence with at least about 98% identity to SEQ ID NO: 34;   r. a heavy chain sequence with at least about 98% identity to SEQ ID NO: 35 and a light chain sequence with at least about 98% identity to SEQ ID NO: 36;   s. a heavy chain sequence with at least about 98% identity to SEQ ID NO: 37 and a light chain sequence with at least about 98% identity to SEQ ID NO: 38; or   t. a heavy chain sequence with at least about 98% identity to SEQ ID NO: 39 and a light chain sequence with at least about 98% identity to SEQ ID NO: 40; and   wherein nicotine-binding antibody or nicotine-binding fragment thereof has a K D  for S-(−)-nicotine of less than about 100 nM.   
     
     
         3 . The nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 2 , wherein the nicotine-binding antibody or nicotine-binding fragment thereof has a K D  for S-(−)-nicotine between 90 nM and 0.05 nM. 
     
     
         4 . The nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 3 , wherein the antibody or fragment is an IgG4. 
     
     
         5 . The nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 4 , wherein the antibody or fragment comprises the substitution S228P. 
     
     
         6 . The nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 3 , wherein the antibody or fragment is a long-acting variant. 
     
     
         7 . The nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 6 , wherein the antibody or fragment is PEGylated. 
     
     
         8 . The nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 1 , wherein the antibody or fragment has a K D  for S-(−)-nicotine of less than about 100 nM. 
     
     
         9 . The nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 1 , wherein the antibody or fragment has a K D  for S-(−)-nicotine of less than about 60 nM. 
     
     
         10 . The nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 1 , wherein the antibody or fragment has a K D  for S-(−)-nicotine of less than about 30 nM. 
     
     
         11 . The nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 1 , wherein the antibody or fragment has a K D  for S-(−)-nicotine of less than about 10 nM. 
     
     
         12 . The nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 1 , wherein the antibody or fragment has a K D  for S-(−)-nicotine of less than about 5 nM. 
     
     
         13 . The nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 1 , wherein the antibody or fragment is substantially not cross-reactive with cotinine. 
     
     
         14 . The nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 3 , wherein the antibody or fragment is substantially not cross-reactive with one or more nicotine-related compounds selected from cotinine, nicotinamide, B-nicotinamide adenine dinucleotide and nornicotine. 
     
     
         15 . A pharmaceutical composition comprising a nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 3  and a pharmaceutically acceptable carrier. 
     
     
         16 . The pharmaceutical composition according to  claim 15 , wherein the composition is formulated for injection or infusion. 
     
     
         17 . A method of treating nicotine addiction or facilitating smoking cessation, comprising administering to a human subject in need thereof a therapeutically effective amount of a nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 3 . 
     
     
         18 . A method of treating nicotine overdose or nicotine poisoning, comprising administering to a mammalian subject in need thereof a therapeutically effective amount of a nicotine-binding antibody or nicotine-binding fragment thereof according to  claim 3 . 
     
     
         19 . The method of  claim 18 , wherein the subject is a human child.