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Last Updated: October 13, 2019

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Claims for Patent: 6,001,588

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Summary for Patent: 6,001,588
Title: Introns and exons of the cystic fibrosis gene and mutations thereof
Abstract:The identification, isolation and cloning of DNA sequences coding for mutant forms of the cystic fibrosis gene and their gene product are described. DNA sequence information and information relating to the genomic structure of the cystic fibrosis gene are provided. The mutant forms of the CF gene include specific sequence alterations in coding portions or of other genetic information at exon/intron boundaries and altered RNA transcripts and mutant protein products. Such DNA and protein information is useful in developing DNA or protein diagnosis for CF mutations, carrier and patient screening, as well as cloning of mutant genes and manufacturing of their proteins for investigation into therapies for cystic fibrosis.
Inventor(s): Tsui; Lap-Chee (Toronto, CA), Rommens; Johanna M. (Willowdale, CA), Kerem; Bat-sheva (Jerusalem, IL)
Assignee: HSC Research Development Corporation (Toronto, CA)
Application Number:07/890,609
Patent Claims:1. A DNA molecule comprising an intronless DNA sequence encoding a mutant CFTR polypeptide, said intronless DNA sequence varying from that of SEQ ID NO:1 in having nucleotide sequence variants resulting in a deletion or alteration of an amino acid in the encoded CFTR polypeptide, so that the sequence of said encoded CFTR polypeptide varies from that of SEQ ID NO:2 in an amino acid residue position selected from the group consisting of amino acid residues 85, 178, 455, 493, 507, 542, 549, 560, and 1092 of SEQ ID NO:2, and wherein an alteration at position 549 is either S549R or S549I.

2. A DNA molecule encoding a mutant CFTR polypeptide, said DNA molecule comprising a sequence which varies from that of SEQ ID NO:1 in having a deletion or alteration of a nucleotide selected from those nucleotides at:

(a) positions 556 and 3659 of SEQ ID NO:1;

(b) the first nucleotide in intron 4 following nucleotide position 621(+1) located in the 3' end of exon 4 of SEQ ID NO:1;

(c) the first nucleotide in intron 5 following nucleotide position 711(+1) located in the 3' end of exon 5 of SEQ ID NO:1; and

(d) the last nucleotide of intron 10 before nucleotide position 1717(-1) located in the 5' end of exon 11 of SEQ ID NO:1.

3. A DNA molecule comprising a DNA sequence selected from the group consisting of:

(a) a portion of a DNA sequence of claim 1, said portion including at least 16 sequential nucleotides and including a nucleotide sequence variant of claim 1 resulting in a deletion or alteration of an amino acid in the encoded CFTR polypeptide, so that the sequence of said encoded CFTR polypeptide varies from that of SEQ ID NO:2 in an amino acid residue position selected from the group consisting of amino acid residues 85, 178, 455, 493, 507, 542, 549, 560 and 1092 of SEQ ID NO:2, and wherein an alteration at position 549 is either S549R or S549I;

(b) a portion of a DNA sequence according to claim 2, said portion including at least 16 sequential nucleotides and including a nucleotide sequence variant which varies from that of SEQ ID NO:1 in having a deletion or alteration of a nucleotide selected from those nucleotides at:

(i) positions 556 and 3659 of SEQ ID NO:1;

(ii) the first nucleotide in intron 4 following nucleotide position 621(+1) located in the 3' end of exon 4 of SEQ ID NO:1;

(iii) the first nucleotide in intron 5 following nucleotide position 711(+1) located in the 3' end of exon 5 of SEQ ID NO:1; and

(iv) the last nucleotide of intron 10 before nucleotide position 1717(-1) located in the 5' end of exon 11 of SEQ ID NO:1;

(c) DNA sequences encoding an epitope comprising a mutant CFTR polypeptide encoded by at least 18 sequential nucleotides in the selected sequence of those sequences recited above in part (a) or part (b).

4. A probe comprising a nucleotide sequence selected from the group of DNA sequences consisting of:

(a) a portion of a DNA sequence of claim 1, said portion including at least 16 sequential nucleotides and including a nucleotide sequence variant of claim 1; and

(b) a portion of a DNA sequence of claim 2, said portion including at least 16 sequential nucleotides and including a nucleocide sequence variant of claim 2.

5. A recombinant cloning vector comprising the DNA molecule of claim 3.

6. A host cell transformed with the vector according to claim 5.

7. A method for producing mutant CFTR polypeptide comprising the steps of:

(a) culturing a host cell of claim 6 in a medium and under conditions favorable for expression of the mutant CFTR polypeptide;

(b) isolating the expressed mutant CFTR polypeptide.

8. A DNA molecule according to claim 1, wherein said alterations in amino acid residues of SEQ ID NO:2 are: G85E, G178R, A455E, Q493X, I507deletion, G542X, R560T, and Y1092X.

9. A DNA molecule according to claim 2, wherein said deletion or alteration of said nucleotides of SEQ ID NO:1 are: A556deleted, C3659deleted, 621(+1G>T), 711(+1G>T) and 1717(-1G>A).

Summary for Patent:   See Pricing

Foriegn Application Priority Data
Foreign Country Foreign Patent Number Foreign Patent Date
Canada2007699Jan 10, 1990
Canada2011253Mar 1, 1990
Canada2020817Jul 10, 1990
PCT Information
PCT FiledJanuary 11, 1991PCT Application Number:PCT/CA91/00009
PCT Publication Date:July 25, 1991PCT Publication Number:WO91/10734

Details for Patent 6,001,588

Applicant Tradename Biologic Ingredient Dosage Form BLA Number Approval Date Patent No. Assignee Estimated Patent Expiration Status Orphan Source
Schering INTRON A interferon alfa-2b VIAL 103132 001 1986-06-04   See Pricing HSC Research Development Corporation (Toronto, CA) 2016-12-14 RX search
Schering INTRON A interferon alfa-2b VIAL 103132 002 1986-06-04   See Pricing HSC Research Development Corporation (Toronto, CA) 2016-12-14 RX search
Schering INTRON A interferon alfa-2b VIAL 103132 003 1986-06-04   See Pricing HSC Research Development Corporation (Toronto, CA) 2016-12-14 RX search
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Number >Approval Date >Patent No. >Assignee >Estimated Patent Expiration >Status >Orphan >Source

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