Compounds and methods for modulating nonclassical cadherin-mediated functions
AssigneeAdherex Technologies, Inc.
InventorsOrest W. Blaschuk, Barbara J. Gour
Life of this patent
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Abstract
Modulating agents for inhibiting or enhancing nonclassical cadherin mediated cell adhesion are provided. The modulating agents comprise one or more of: (a) a peptide sequence that is at least 50% identical to a nonclassical cadherin CAR sequence; (b) a non-peptide mimetic of a nonclassical cadherin CAR sequence; (c) a substance, such as an antibody or antigen-binding fragment thereof, that specifically binds a nonclassical cadherin CAR sequence; and/or (d) a polynucleotide encoding a polypeptide that comprises a nonclassical cadherin CAR sequence or analogue thereof. Methods for using such modulating agents for modulating nonclassical cadherin-mediated cell adhesion in a variety of contexts are also provided.
Claims117
A modulating agent that:
- (a) comprises a nonclassical cadherin CAR sequence;
- and
- (b) contains 3-16 amino acid residues linked by peptide bonds.
A modulating agent that:
- (a) comprises at least five consecutive amino acid residues of a nonclassical cadherin CAR sequence having the formula:
- Aaa-Phe-Baa-Ile/Leu/Val-Asp/Asn/Glu-Caa-Daa-Ser/Thr/Asn-Gly (SEQ ID NO:3)
- wherein Aaa, Baa, Caa and Daa are independently selected amino acid residues;
- Ile/Leu/Val is an amino acid that is selected from the group consisting of isoleucine, leucine and valine, Asp/Asn/Glu is an amino acid that is selected from the group consisting of aspartate, asparagine and glutamate;
- and Ser/Thr/Asn is an amino acid that is selected from the group consisting of serine, threonine and asparagine;
- and
- (b) contains no more than 50 consecutive amino acid residues present within the nonclassical cadherin.
A modulating agent that:
- (a) comprises a nonclassical cadherin CAR sequence having the formula:
- Aaa-Phe-Baa-Ile/Leu/Val-Asp/Asn/Glu-Caa-Daa-Ser/Thr/Asn-Gly (SEQ ID NO:3)
- wherein Aaa, Baa, Caa and Daa are independently selected amino acid residues;
- Ile/Leu/Val is an amino acid that is selected from the group consisting of isoleucine, leucine and valine, Asp/Asn/Glu is an amino acid that is selected from the group consisting of aspartate, asparagine and glutamate;
- and Ser/Thr/Asn is an amino acid that is selected from the group consisting of serine, threonine or asparagine;
- and
- (b) contains no more than 50 consecutive amino acid residues present within the nonclassical cadherin.
A modulating agent that:
- (a) comprises at least nine consecutive amino acid residues of a nonclassical cadherin, wherein the nine consecutive amino acids comprise a nonclassical cadherin CAR sequence having the formula:
- Aaa-Phe-Baa-Ile/Leu/Val-Asp/Asn/Glu-Caa-Daa-Ser/Thr/Asn-Gly (SEQ ID NO:3)
- wherein Aaa, Baa, Caa and Daa are independently selected amino acid residues;
- Ile/Leu/Val is an amino acid that is selected from the group consisting of isoleucine, leucine and valine, Asp/Asn/Glu is an amino acid that is selected from the group consisting of aspartate, asparagine and glutamate;
- and Ser/Thr/Asn is an amino acid that is selected from the group consisting of serine, threonine and asparagine;
- and
- (b) contains no more than 50 consecutive amino acid residues present within the nonclassical cadherin.
A modulating agent comprising an antibody or antigen-binding fragment thereof that specifically binds to a nonclassical cadherin CAR sequence and modulates a nonclassical cadherin-mediated function, wherein the nonclassical cadherin CAR sequence has the formula:
- Aaa-Phe-Baa-Ile/Leu/Val-Asp/Asn/Glu-Caa-Daa-Ser/Thr/Asn-Gly (SEQ ID NO:3)
- wherein Aaa, Baa, Caa and Daa are independently selected amino acid residues;
- Ile/Leu/Val is an amino acid that is selected from the group consisting of isoleucine, leucine and valine, Asp/Asn/Glu is an amino acid that is selected from the group consisting of aspartate, asparagine and glutamate;
- and Ser/Thr/Asn is an amino acid that is selected from the group consisting of serine, threonine and asparagine;
- and
- wherein the modulating agent inhibits or enhances a function mediated by the nonclassical cadherin.
A modulating agent comprising a mimetic of a nonclassical cadherin CAR sequence that comprises at least three consecutive amino acid residues of a nonclassical cadherin CAR sequence having the formula
- Aaa-Phe-Baa-Ile/Leu/Val-Asp/Asn/Glu-Caa-Daa-Ser/Thr/Asn-Gly (SEQ ID NO:3)
- wherein Aaa, Baa, Caa and Daa are independently selected amino acid residues;
- Ile/Leu/Val is an amino acid that is selected from the group consisting of isoleucine, leucine and valine, Asp/Asn/Glu is an amino acid that is selected from the group consisting of aspartate, asparagine and glutamate;
- and Ser/Thr/Asn is an amino acid that is selected from the group consisting of serine, threonine and asparagine;
- wherein the mimetic is capable of modulating a nonclassical cadherin-mediated function.
A modulating agent comprising a mimetic of a nonclassical cadherin CAR sequence that comprises at least five consecutive amino acid residues of a nonclassical cadherin CAR sequence having the formula
- Aaa-Phe-Baa-Ile/Leu/Val-Asp/Asn/Glu-Caa-Daa-Ser/Thr/Asn-Gly (SEQ ID NO:3)
- wherein Aaa, Baa, Caa and Daa are independently selected amino acid residues;
- Ile/Leu/Val is an amino acid that is selected from the group consisting of isoleucine, leucine and valine, Asp/Asn/Glu is an amino acid that is selected from the group consisting of aspartate, asparagine and glutamate;
- and Ser/Thr/Asn is an amino acid that is selected from the group consisting of serine, threonine and asparagine;
- wherein the mimetic is capable of modulating a nonclassical cadherin-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to an OB-cadherin CAR sequence selected from the group consisting of IFVIDDKSG (SEQ ID NO:85), FFVIEEYTG (SEQ ID NO:99) and YFSVEAQTG (SEQ ID NO:113) and
- (b) modulates an OB-cadherin-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to the cadherin-5 CAR sequence VFRVDAETG (SEQ ID NO:127);
- and
- (b) modulates a cadherin-5-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to a cadherin-6 CAR sequence selected from the group consisting of FFLLEEYTG (SEQ ID NO:154), LFIINENTG (SEQ ID NO:141), YFSVESETG (SEQ ID NO:168) and IFNIDSGNG (SEQ ID NO:182);
- and
- (b) modulates a cadherin-6-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to a cadherin-7 CAR sequence selected from the group consisting of IFIIDENTG (SEQ ID NO:196), YFSVEPKTG (SEQ ID NO:210) and YFNIDANSG (SEQ ID NO:224);
- and
- (b) modulates a cadherin-7-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to a cadherin-8 CAR sequence selected from the group consisting of MFVLEEFSG (SEQ ID NO:252) and IFQINDVTG (SEQ ID NO:238);
- and
- (b) modulates a cadherin-8-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to a cadherin-12 CAR sequence selected from the group consisting of VFTIDETTG (SEQ ID NO:266) and YFSIDPKTG (SEQ ID NO:280);
- and
- (b) modulates a cadherin-12-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to a cadherin-14 CAR sequence selected from the group consisting of IFIIDDTTG (SEQ ID NO:294), YFSVDPKTG (SEQ ID NO:308) and FFNIDANTG (SEQ ID NO:319) and
- (b) modulates a cadherin-14-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to a cadherin-15 CAR sequence selected from the group consisting of VFSIDKFTG (SEQ ID NO:333) and LFSIDELTG (SEQ ID NO:347);
- and
- (b) modulates a cadherin-15-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to the T-cadherin CAR sequence IFRINENTG (SEQ ID NO:361);
- and
- (b) modulates a T-cadherin-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to a PB-cadherin CAR sequence selected from the group consisting of FFVVEEYTG (SEQ ID NO:375), IFLIDELTG (SEQ ID NO:389), HFTVDPKTG (SEQ ID NO:403) and IFDIDADTG (SEQ ID NO:417);
- and
- (b) modulates a PB-cadherin-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to the LI-cadherin CAR sequence YFQINNKTG (SEQ ID NO:431);
- and
- (b) modulates a LI-cadherin-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to a protocadherin CAR sequence selected from the group consisting of LFALDLVTG (SEQ ID NO:445), YFTINRDNG (SEQ ID NO:459), LFSIDPKTG (SEQ ID NO:473) and LFEIDPSSG (SEQ ID NO:489);
- and
- (b) modulates a protocadherin-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to a desmoglein CAR sequence selected from the group consisting of IFVINQKTG (SEQ ID NO:503), MFIINRNTG (SEQ ID NO:517) and VFYLNKDTG (SEQ ID NO:531);
- and
- (b) modulates a desmoglein-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to a desmocollin CAR sequence selected from the group consisting of LFYIEKDTG (SEQ ID NO:545), LFYVERDTG (SEQ ID NO:559) and LFYIERDTG (SEQ ID NO:571);
- and
- (b) modulates a desmocollin-mediated function.
A modulating agent comprising an antibody or antigen-binding fragment thereof that:
- (a) specifically binds to a cadherin-related neuronal receptor CAR sequence selected from the group consisting of KFHIDPVSG (SEQ ID NO:585), QFSIDADTG (SEQ ID NO:599), TFHIDSVSG (SEQ ID NO:613), AFNIDSNSG (SEQ ID NO:627), KFTIDSSSG (SEQ ID NO:641), LFTLDEKNG (SEQ ID NO:655) and KFLINEKTG (SEQ ID NO:4052);
- and
- (b) modulates a cadherin-related neuronal receptor-mediated function.
Dependencies are inferred from the claim text.