US2023036052A1PendingUtilityA1

Modified protein

59
Assignee: PNEUMAGEN LTDPriority: Jan 9, 2018Filed: Sep 6, 2022Published: Feb 2, 2023
Est. expiryJan 9, 2038(~11.5 yrs left)· nominal 20-yr term from priority
Inventors:Helen ConnarisJane Alexandra Potter
C07K 14/315A61P 35/00C07K 14/3156A61K 39/39A61K 38/00A61K 2039/55516C07K 14/28A61P 37/02C07K 2319/00C12N 9/2402C07K 2319/20C07K 14/195Y02A50/30
59
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Claims

Abstract

The present disclosure a cohort of sialic acid binding molecules which comprise one or more modified carbohydrate binding modules (CBMs). The modified CBMs reduce the risk of adverse events related to the host immune response and/or the production of anti-drug antibodies (ADAs). The modified CBMs can be used in therapy or as medicaments and find specific application as molecules for the modulation of an immune response and/or cell growth. The modified CBMs may also be used as adjuvants, for example mucosal adjuvants and in the treatment and/or prevention of cancer, sepsis and/or diseases caused or contributed to by a pathogen that binds cell surface sialic acid-containing receptors.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A sialic acid binding molecule comprising one or more modified family 40 carbohydrate binding module(s) (CBM40(s)). 
     
     
         2 . The sialic acid binding molecule of  claim 1 , wherein the molecule comprises two modified CBM40s. 
     
     
         3 . The sialic acid binding molecule of  claim 1 , wherein each modified CBM40 comprises one or more mutations relative to a reference sequence. 
     
     
         4 . The sialic acid binding molecule of  claim 3 , wherein the reference sequence is selected from the group consisting of:
 (i) a wild type family 40 CBM sequence;   (ii) a wild type CBM40 sequence from  Vibrio cholerae;      (iii) the NanH sialidase sequence of  Vibrio cholerae;      (iv) a wild type CBM40 sequences from  Streptococcus pneumoniae;      (v) the NanA sialidase sequence of  Streptococcus pneumoniae;      (vi) the sequence of SEQ ID NO: 1;   (vii) the sequence of SEQ ID NO: 2;   (viii) the sequence of SEQ ID NO: 3; and   (ix) the sequence of SEQ ID NO: 4.   
     
     
         5 . The sialic acid binding molecule of  claim 3 , wherein the mutation is selected from the group consisting of:
 (i) one or more amino acid substitution(s);   (ii) one or more amino acid deletion(s);   (iii) one or more amino acid addition(s)/insertion(s);   (iv) one or more amino acid/sequence inversions; and   (v) one or more amino acid/sequence duplications.   
     
     
         6 . The sialic acid binding molecule of  claim 1 , wherein the sialic acid binding molecule further comprises a modified oligomerisation domain. 
     
     
         7 . The sialic acid binding molecule of  claim 6 , wherein the modified oligomerisation domain contains one or more mutations relative to a reference sequence. 
     
     
         8 . The sialic acid binding molecule of  claim 7 , wherein the reference sequence is selected from the group consisting of:
 (i) a wild type  Pseudomonas aeruginosa  pseudaminidase sequence;   (ii) the  Pseudomonas aeruginosa  pseudaminidase amino acid sequence deposited under accession number Q9L6G4;   (iii) the sequence of SEQ ID NO: 13; and   (iv) the sequence of SEQ ID NO: 14.   
     
     
         9 . The sialic acid binding molecule of  claim 1 , wherein the sialic acid molecule modulates IL-8 expression. 
     
     
         10 . The sialic acid binding molecule of  claim 1 , wherein the sialic acid binding molecule inhibits IL-8 expression. 
     
     
         11 . The sialic acid binding molecule of  claim 1 , wherein the sialic acid binding molecule inhibits IL-8 expression in A549 cells. 
     
     
         12 . The sialic acid binding molecule of  claim 1 , wherein relative to the CBM sequence of SEQ ID NO: 1, the modified CBM comprises amino acid substitution(s) within one or more of the amino acid regions selected from the group consisting of:
 aa 127-135 of SEQ ID NO: 1;   aa 146-178 of SEQ ID NO: 1;   aa 182-196 of SEQ ID NO: 1;   aa 204-228 of SEQ ID NO: 1;   aa 239-254 of SEQ ID NO: 1;   aa 257-265 of SEQ ID NO: 1;   aa 267-275 of SEQ ID NO: 1; and   aa 284-300 of SEQ ID NO: 1.   
     
     
         13 . The sialic acid binding molecule of  claim 1 , wherein the modified CBM40 is derived from the CBM sequence of SEQ ID NO: 1 and relative to the CBM sequence of SEQ ID NO:
 1 the modified CBM40 of the sialic acid binding molecule comprises amino acid substitution(s) at any one or more of”   aa 162 of SEQ ID NO: 1;   aa 239 of SEQ ID NO: 1; and   aa 246 of SEQ ID NO: 1.   
     
     
         14 . The sialic acid binding molecule of  claim 1 , wherein the modified CBM40 is derived from the CBM sequence of SEQ ID NO: 1 and relative to the CBM sequence of SEQ ID NO: 1 the modified CBM40 of the sialic acid binding molecule comprises a substitution of the alanine residue at position 162 with a proline residue. 
     
     
         15 . The sialic acid binding molecule of  claim 1 , wherein the modified CBM40 is derived from the CBM sequence of SEQ ID NO: 1 and relative to the CBM sequence of SEQ ID NO:
 1 the modified CBM40 of the sialic acid binding molecule comprises:   a substitution of the alanine residue at position 162 with a proline residue;   a substitution of the valine residue at position 239 with an alanine residue; and   a substitution of the valine residue at position 246 of with a glycine residue.   
     
     
         16 . The sialic acid binding molecule of  claim 7 , wherein the modified oligomerisation domain is derived from the oligomerisation domain sequence of SEQ ID NO: 13 and relative to the oligomerisation domain of SEQ ID NO: 13 the modified oligomerisation domain of the sialic acid binding molecule comprises:
 an amino acid substitution at position 342; and/or   an amino acid substitution at position 239.   
     
     
         17 . The sialic acid binding molecule of  claim 7 , wherein the modified oligomerisation domain is derived from the oligomerisation domain sequence of SEQ ID NO: 13 and relative to the oligomerisation domain of SEQ ID NO: 13 the modified oligomerisation domain of the sialic acid binding molecule comprises:
 a substitution of the serine residue at position 342 with an aspartate residue; and   a substitution of the valine residue at position 239 with a lysine residue.   
     
     
         18 . A method of modulating IL-8 expression, said method comprising administering a subject an IL-8 expression modulating amount of the sialic acid binding molecule of  claim 1 . 
     
     
         19 . A CBM variant of SEQ ID NO: 1, wherein said variant inhibits IL-8 expression and the amino acid sequence of said variant CBM differs from SEQ ID NO:1 by one or more amino acid mutations. 
     
     
         20 . The CBM variant of  claim 19 , wherein the variant CBM differs from SEQ ID NO: 1 by at least an A162P mutation. 
     
     
         21 . The CBM variant of  claim 19 , wherein the variant inhibits IL-8 expression in an A549 cell. 
     
     
         22 . A sialic acid binding molecule comprising the CBM variant of  claim 19 . 
     
     
         23 . The sialic acid binding molecule of  claim 22 , wherein the molecule comprises two modified CBM40s. 
     
     
         24 . The sialic acid binding molecule of  claim 22 , wherein the sialic acid binding molecule further comprises a modified oligomerisation domain. 
     
     
         25 . The sialic acid binding molecule of  claim 24 , wherein the modified oligomerisation domain contains one or more mutations relative to a reference oligomerisation domain sequence.

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