CD40 splice variants, compositions for making and methods of using the same
First Claim
1. An isolated protein having the amino acid sequence selected from the group consisting of:
- i) SEQ ID NO;
5;
ii) a fragment of SEQ ID NO;
5 comprising at least 10 amino acids including at least 4 amino acids of the unique tail of SEQ ID NO;
5;
iii) SEQ ID NO;
6;
iv) a fragment of SEQ ID NO;
6 comprising at least 10 amino acids including at least 4 amino acids of the unique tail of SEQ ID NO;
6;
v) SEQ ID NO;
7;
vi) an amino acid sequence having at least 10 amino acids and 90% identity with any one of the sequences of i)-v); and
vii) an amino acid sequence having at least about 95% identity with any one of the sequences of i)-v).
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Accused Products
Abstract
Provided are isolated CD40 splice variants that include altered internal sequences and unique tail sequences relative to previously described CD40 protein sequences. Also provided are fragments of the CD40 splice variants comprising at least 10 amino acids including at least 4 amino acids of the unique tail sequence; the unique tail sequences, and homologues thereof having at least 10 amino acids and 90% identity and antibodies which bind to an epitope on such proteins are disclosed. Pharmaceutical compositions comprising the protein, antibodies, isolated nucleic acid molecule that encode such proteins and pharmaceutical composition comprising such nucleic acid molecules are also disclosed. The present invention additionally relates to recombinant expression vectors that include the nucleic acid molecules and host cells which comprise such recombinant expression vectors are disclosed. In vitro methods of detecting in a sample the presence and/or quantity of such proteins or transcript which encodes such proteins are disclosed as are kits and reagents for performing the methods. Methods of modulating CD40-CD154 interactions in an individual are disclosed.
19 Citations
51 Claims
-
1. An isolated protein having the amino acid sequence selected from the group consisting of:
-
i) SEQ ID NO;
5;
ii) a fragment of SEQ ID NO;
5 comprising at least 10 amino acids including at least 4 amino acids of the unique tail of SEQ ID NO;
5;
iii) SEQ ID NO;
6;
iv) a fragment of SEQ ID NO;
6 comprising at least 10 amino acids including at least 4 amino acids of the unique tail of SEQ ID NO;
6;
v) SEQ ID NO;
7;
vi) an amino acid sequence having at least 10 amino acids and 90% identity with any one of the sequences of i)-v); and
vii) an amino acid sequence having at least about 95% identity with any one of the sequences of i)-v). - View Dependent Claims (2, 3, 4, 5, 6, 26, 27, 28, 29, 30, 31, 47)
-
-
7. An isolated nucleic acid molecule comprising the nucleotide sequence selected from the group consisting of:
-
i) SEQ ID NO;
1;
ii) a fragment of SEQ ID NO;
1 that encodes at least 10 amino acids of SEQ ID NO;
5 including at least 4 amino acids of the unique tail of SEQ ID NO;
5;
iii) SEQ ID NO;
2;
iv) SEQ ID NO;
3;
v) a fragment of SEQ ID NO;
3 that encodes at least 10 amino acids of SEQ ID NO;
6 including at least 4 amino acids of the unique tail of SEQ ID NO;
6;
vi) SEQ ID NO;
4; and
vii) a fragment of SEQ ID NO;
4 that encodes at least 10 amino acids of SEQ ID NO;
7;
- View Dependent Claims (8, 9, 10, 11, 12, 13, 14, 15)
-
-
16. An isolated antibody that specifically binds to an epitope on SEQ ID NOs:
- 5, 6 or 7
wherein the isolated antibody does not bind to an epitope consisting of an amino acid fragment of SEQ ID NO;
14.a. The antibody of claim 16, wherein said epitope includes at least 4 amino acids from the unique tail of SEQ ID NO;
5;
or at least 4 amino acids from the unique tail of SEQ ID NO;
6. - View Dependent Claims (17, 18, 19, 20, 21)
- 5, 6 or 7
-
22. A method of detecting whether an individual is expressing a protein, the method comprising
detecting in a sample from the individual a transcript that encodes a protein selected from the group consisting of SEQ ID NO: - 5-7,
wherein detection of the transcript in a sample is indicative of expression of said protein by said individual. - View Dependent Claims (23, 24, 25)
- 5-7,
-
32. An isolated chimeric polypeptide comprising a first amino acid sequence being at least 95% homologous to amino acids 1-135 of wild-type CD40 (SEQ ID NO:
- 14), and a second amino acid sequence being at least 95% homologous to a polypeptide having the sequence VRPKTWLCNRQAQTRLMLSVVSPGQWALEKA (SEQ ID NO;
20), wherein the first and said second amino acid sequences are contiguous and in a sequential order. - View Dependent Claims (33, 34, 35, 36, 48)
- 14), and a second amino acid sequence being at least 95% homologous to a polypeptide having the sequence VRPKTWLCNRQAQTRLMLSVVSPGQWALEKA (SEQ ID NO;
- 37. An isolated polypeptide comprising an amino acid sequence at least 95% identical to a polypeptide having the sequence VRPKTWLCNRQAQTRLMLSVVSPGQWALEKA (SEQ ID NO:
-
38. An isolated chimeric polypeptide, including a first amino acid sequence being at least 95% homologous to amino acids 1-134 of WT CD40 (SEQ ID NO:
- 14), and a second amino acid sequence being at least 95% homologous to a polypeptide having the sequence DICQPHFPKDRGLNLLM (SEQ ID NO;
24), wherein the first and said second amino acid sequences are contiguous and in a sequential order. - View Dependent Claims (39, 40, 41, 42, 43, 50, 51)
- 14), and a second amino acid sequence being at least 95% homologous to a polypeptide having the sequence DICQPHFPKDRGLNLLM (SEQ ID NO;
-
44. An isolated polypeptide comprising an amino acid sequence at least 95% identical to a polypeptide having the sequence
DICQPHFPKDRGLNLLM (SEQ ID NO: - 24).
-
45. An isolated chimeric polypeptide encoding for VAR3 (SEQ ID NO:
- 7), comprising a first amino acid sequence being at least 95% homologous to amino acids 1-186 of wild-type CD40 corresponding to GI;
15214587 (SEQ ID NO;
14), which also corresponds to amino acids 1-186 of SEQ ID NO;
7 corresponding to VAR3, bridged by E and a second amino acid sequence being at least 95% homologous to amino acids 215-177 of wild-type CD40 corresponding to GI;
15214587 (SEQ ID NO;
14), which also corresponds to amino acids 188-248 of SEQ ID NO;
7 corresponding to VAR3, wherein said first amino acid sequence is contiguous to said bridging amino acid and said second amino acid sequence is contiguous to said bridging amino acid, and wherein said first amino acid, said bridging amino acid and said second amino acid sequence are in a sequential order.
- 7), comprising a first amino acid sequence being at least 95% homologous to amino acids 1-186 of wild-type CD40 corresponding to GI;
-
46. An isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO:
- 7, comprising a polypeptide having a length “
n”
, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise CEK (where C is the last amino acid of the WT fragment before the edge and K is the first amino acid of the WT fragment after the edge, E is the bridging amino acid), having a structure as follows (numbering according to SEQ ID NO;
7);
a sequence starting from any of amino acid numbers 186−
x to; and
ending at any of amino acid numbers 188+((n−
2)−
x), in which x varies from 0 to n−
2, such that the fragment does not extend beyond the last amino acid of SEQ ID NO;
7.
- 7, comprising a polypeptide having a length “
Specification