US 11,945,858 B2
Antibodies and antibody fragments against HNAV1.7 channel and their use in pain and cancer indications
Marzia Martina, Ottawa (CA); Balu Chakravarthy, Ottawa (CA); Yves Durocher, Montreal (CA); Mehdi Arbabi-Ghahroudi, Ottawa (CA); Anne Marcil, Pierrefonds (CA); Danica Stanimirovic, Ottawa (CA); Traian Sulea, Kirkland (CA); Maria Moreno, Ottawa (CA); and Umberto Banderali, Ottawa (CA)
Assigned to NATIONAL RESEARCH COUNCIL OF CANADA, Ottawa (CA)
Appl. No. 17/056,243
Filed by NATIONAL RESEARCH COUNCIL OF CANADA, Ottawa (CA)
PCT Filed May 17, 2019, PCT No. PCT/CA2019/050676
§ 371(c)(1), (2) Date Nov. 17, 2020,
PCT Pub. No. WO2019/218082, PCT Pub. Date Nov. 21, 2019.
Claims priority of provisional application 62/673,210, filed on May 18, 2018.
Prior Publication US 2021/0206842 A1, Jul. 8, 2021
Int. Cl. A61K 39/395 (2006.01); A61P 29/00 (2006.01); C07K 16/00 (2006.01); C07K 16/18 (2006.01); C07K 16/46 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/18 (2013.01) [A61P 29/00 (2018.01); A61K 2039/505 (2013.01); C07K 2317/22 (2013.01); C07K 2317/33 (2013.01); C07K 2317/565 (2013.01); C07K 2317/569 (2013.01); C07K 2317/92 (2013.01)] 18 Claims
 
1. An antibody or antigen-binding fragment that binds specifically to loop 3 of a domain I (DI) of a Nav 1.7 polypeptide, and which inhibits the flux of Na+ through an hNAv 1.7 channel,
wherein the antibody comprises three variable heavy domain complementarity determining regions (CDR)(CDR H1, H2 and H3), and three variable light domain CDR (CDR L1, L2 and L3), said CDR H1, H2, H3, L1, L2, and L3 comprising the amino acid sequences:
CDR H1: GYTFTNYW (SEQ ID NO:7),
CDR H2: INPSNGRA (SEQ ID NO:8),
CDR H3: ARSPYGYYDY (SEQ ID NO:9),
CDR L1: QSLLHSNGNTY (SEQ ID NO:13),
CDR L2: KVS (SEQ ID NO:14), and
CDR L3: SQITHVPLT (SEQ ID NO:15); respectively;
or
CDR H1: GFSLSRYN (SEQ ID NO:75),
CDR H2: IWGGGST (SEQ ID NO:76),
CDR H3: ARNGANWDWFAY (SEQ ID NO:77),
CDR L1: QSLLYSSNQKNY (SEQ ID NO:80),
CDR L2: WAS (SEQ ID NO:81), and
CDR L3: QQYYSYPFT (SEQ ID NO:82), respectively;
or
CDR H1: GYTFTTYW (SEQ ID NO: 85),
CDR H2: INPSNGRA (SEQ ID NO:86),
CDR H3: LRSLGYFDY (SEQ ID NO:87),
CDR L1: QSLVHSNGNTY (SEQ ID NO:90),
CDR L2: KVS (SEQ ID NO:91), and
CDR L3: SQSTHVPYT (SEQ ID NO:92), respectively;
or
CDR H1: GFTFRSYA (SEQ ID NO:95),
CDR H2: ISSGGST (SEQ ID NO:96),
CDR H3: ARGYDGYYERIWYYAMDY (SEQ ID NO:97),
CDR L1: QNVGTI (SEQ ID NO:100),
CDR L2: SAS (SEQ ID NO:101), and
CDR L3: QQYNTYPLT (SEQ ID NO:102), respectively;
and
wherein said antigen-binding fragment comprises three variable domain complementarity determining regions (CDR)(CDR 1, 2 and 3), comprising the amino acid sequences
CDR 1: GFAFSSAP (SEQ ID NO:39),
CDR 2: IESDQDHTI (SEQ ID NO:40), and
CDR 3: QKRGEKKT (SEQ ID NO:41), respectively.