US 2003/0069408 A1Published application

Human nodal and lefty homologues

AssigneeHuman Genome Sciences, Inc.

InventorsReinhard Ebner, Daniel R. Soppet, Steven M. Ruben

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Abstract

The present invention relates to novel Nodal and Lefty proteins which are members of the TGF-β family. In particular, isolated nucleic acid molecules are provided encoding the human Nodal and Lefty proteins. Nodal and Lefty polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of Nodal and Lefty activity. Also provided are diagnostic methods for detecting cell growth and differentiation-related disorders and therapeutic methods for treating cell growth and differentiation-related disorders.

Claims36

Dependent claims

An isolated nucleic acid molecule nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of:

(a) a nucleotide sequence encoding the Nodal polypeptide having the complete amino acid sequence in SEQ ID NO:2 (i.e., positions 1 to 283 of SEQ ID NO:2);
(b) a nucleotide sequence encoding the predicted active Nodal polypeptide having the amino acid sequence at positions 173 to 283 of SEQ ID NO:2;
(c) a nucleotide sequence encoding the Nodal polypeptide having the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209092 or 209135;
(d) a nucleotide sequence encoding the active domain of the Nodal polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209092 or 209135;
(e) a nucleotide sequence encoding the Lefty polypeptide having the complete amino acid sequence in SEQ ID NO:4 (i.e., positions −18 to 348 of SEQ ID NO:4);
(f) a nucleotide sequence encoding the Lefty polypeptide having the complete amino acid sequence in SEQ ID NO:4 excepting the N-terminal methionine (i.e., positions −17 to 348 of SEQ ID NO:4);
(g) a nucleotide sequence encoding the predicted active domain of the Lefty polypeptide having the amino acid sequence at positions 60 to 348 of SEQ ID NO:4;
(h) a nucleotide sequence encoding the predicted active domain of the Lefty polypeptide having the amino acid sequence at positions 118 to 348 of SEQ ID NO:4;
(i) a nucleotide sequence encoding the predicted active domain of the Lefty polypeptide having the amino acid sequence at positions 125 to 348 of SEQ ID NO:4;
(j) a nucleotide sequence encoding the Lefty polypeptide having the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No.209091;
(k) a nucleotide sequence encoding the Lefty polypeptide having the complete amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone contained in ATCC Deposit No. 209091;
(l) a nucleotide sequence encoding the active domain of the Lefty polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209091;
and,
(m) a nucleotide sequence complementary to any of the nucleotide sequences in (a) through (l) above.

11 more elements

An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of:

(a) a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of residues n-348 of SEQ ID NO:4, where n is an integer in the range of 1-60;
(b) a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of residues n-348 of SEQ ID NO:4, where n is an integer in the range of 1-118;
(c) a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of residues n-348 of SEQ ID NO:4, where n is an integer in the range of 1-125;
(d) a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of residues 1-m of SEQ ID NO:4, where m is an integer in the range of 335-348;
(e) a nucleotide sequence encoding a polypeptide having the amino acid sequence consisting of residues n-m of SEQ ID NO:4, where n and m are integers as defined respectively in (a) through (d) above;
(f) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete Lefty amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209091 wherein said portion excludes from 1 to about 78 amino acids from the amino terminus of said complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209091;
(g) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete Lefty amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209091 wherein said portion excludes from 1 to about 136 amino acids from the amino terminus of said complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209091;
(h) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete Lefty amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209091 wherein said portion excludes from 1 to about 143 amino acids from the amino terminus of said complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209091;
(i) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete Lefty amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209091 wherein said portion excludes from 1 to about 13 amino acids from the carboxy terminus of said complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209091;
and
(j) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete Lefty amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209091 wherein said portion include a combination of any of the amino terminal and carboxy terminal deletions in (f) through (i), above.

8 more elements

An isolated Nodal and Lefty polypeptide comprising an amino acid sequence at least 95% identical to a sequence selected from the group consisting of:

(a) the amino acid sequence of the full-length Nodal polypeptide having the complete amino acid sequence shown in SEQ ID NO:2 (i.e., positions 1 to 283 of SEQ ID NO:2);
(b) the amino acid sequence of the predicted active Nodal polypeptide having the amino acid sequence at positions 173 to 283 of SEQ ID NO:2;
(c) the amino acid sequence of the Nodal polypeptide having the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209092 or 209135;
(d) the amino acid sequence of the active domain of the Nodal polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209092 or 209135;
(e) the amino acid sequence of the Lefty polypeptide having the complete amino acid sequence in SEQ ID NO:4 (i.e., positions −18 to 348 of SEQ ID NO:4);
(f) the amino acid sequence of the Lefty polypeptide having the complete amino acid sequence in SEQ ID NO:4 excepting the N-terminal methionine (i.e., positions −17 to 348 of SEQ ID NO:4);
(g) the amino acid sequence of the predicted active domain of the Lefty polypeptide having the amino acid sequence at positions 60 to 348 of SEQ ID NO:4;
(h) the amino acid sequence of the predicted active domain of the Lefty polypeptide having the amino acid sequence at positions 118 to 348 of SEQ ID NO:4;
(i) the amino acid sequence of the predicted active domain of the Lefty polypeptide having the amino acid sequence at positions 125 to 348 of SEQ ID NO:4;
(j) the amino acid sequence of the Lefty polypeptide having the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No.209091;
(k) the amino acid sequence of the Lefty polypeptide having the complete amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone contained in ATCC Deposit No. 209091, and;
(l) the amino acid sequence of the active domain of the Lefty polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209091.

9 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/166,183Filed 11 Jun 2002
Priority: 21 Aug 1997
Published: 10 Apr 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification12 codes

C07K 14/47
From vertebrates: from mammals
A61P 17/02
Drugs for dermatological disorders: for treating wounds, ulcers, burns, scars, keloids, or the like
A61P 35/00
Antineoplastic agents
C07K 14/495
Growth factors; Growth regulators: transforming growth factor [TGF]

Family

Application60/056,565Us provisional application · filed 21 Aug 1997
Application09/137,415Continuation · filed 20 Aug 1998
Application10/166,183Continuation · filed 11 Jun 2002
US 2002/0086351 A1Published application
US 2003/0069408 A1This patent

From the US filing history. Foreign family members aren’t listed.

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