Stem cell growth factor-like polypeptide

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues

Reexamination Certificate

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C530S351000, C530S399000, C536S023100, C536S023500, C435S810000, C435S975000

Reexamination Certificate

active

06667391

ABSTRACT:

TECHNICAL FIELD
The present invention provides novel polynucleotides and proteins encoded by such polynucleotides, along with uses for these polynucleotides and proteins, for example in therapeutic, diagnostic and research methods. In particular, the invention relates to a novel human stem cell growth factor-like protein.
BACKGROUND ART
Technology aimed at the discovery of protein factors (including e.g., cytokines, such as lymphokines, interferons, CSFs, chemokines, and interleukins) has matured rapidly over the past decade. The now routine hybridization cloning and expression cloning techniques clone novel polynucleotides “directly” in the sense that they rely on information directly related to the discovered protein (i.e., partial DNA/amino acid sequence of the protein in the case of hybridization cloning; activity of the protein in the case of expression cloning). More recent “indirect” cloning techniques such as signal sequence cloning, which isolates DNA sequences based on the presence of a now well-recognized secretory leader sequence motif, as well as various PCR-based or low stringency hybridization-based cloning techniques, have advanced the state of the art by making available large numbers of DNA/amino acid sequences for proteins that are known to have biological activity, for example, by virtue of their secreted nature in the case of leader sequence cloning, by virtue of their cell or tissue source in the case of PCR-based techniques, or by virtue of structural similarity to other genes of known biological activity.
Identified polynucleotide and polypeptide sequences have numerous applications in, for example, diagnostics, forensics, gene mapping; identification of mutations responsible for genetic disorders or other traits, to assess biodiversity, and to produce many other types of data and products dependent on DNA and amino acid sequences.
SUMMARY OF THE INVENTION
The compositions of the present invention include novel isolated polypeptides, novel isolated polynucleotides encoding such polypeptides, including recombinant DNA molecules, cloned genes or degenerate variants thereof, especially naturally occurring variants such as allelic variants, antisense polynucleotide molecules, and antibodies that specifically recognize one or more epitopes present on such polypeptides, as well as hybridomas producing such antibodies. Specifically, the polynucleotides of the present invention are based on polynucleotides isolated from cDNA libraries prepared from human fetal liver spleen (Hyseq clone identification number 6118092), ovary (Hyseq clone identification number 8375786), adult brain (Hyseq clone identification numbers 701734, 15327638, 15741682, 15954941, 15955015), lung tumor (Hyseq clone identification number 11047146 and 10280328), spinal cord (Hyseq clone identification number 10102150), cervix (Hyseq clone identification numbers 10022437 and 14029194), ovary (Hyseq clone identification number 8319153), endothelial cells (Hyseq clone identification number 13815744), umbilical cord (Hyseq clone identification number 18568149), lymphocyte (Hyseq clone identification number 10257378), lung fibroblast (Hyseq clone identification number 17116257), fetal brain (Hyseq clone identification number 15266959), and testis.
Using Hyseq's sequencing by hybridization signature analysis, very closely related polynucleotides are expected to be isolated from human fetal liver-spleen (Hyseq clone identification numbers 6118092, 6118141, 324694, 139790, 388618), stomach (Hyseq clone identification number 11423449), endothelial cells (Hyseq clone identification numbers 13773559, 13815744, 13841093), adult brain (Hyseq clone identification numbers 737767, 701734, 16127344, 15198141, 15208858, 15554838, 15946615, 15296366, 15321434, 15741682, 15841267, 15855073, 15726537, 15955015, 15327638, 15954941, 16344372), bone marrow (Hyseq clone identification numbers 114762120625288, 20798194, 16463779), adult kidney (Hyseq clone identification numbers 2405528 and 2305428), adult spleen (Hyseq clone identification numbers 2972973, 2956887, 14377989, 14476605, 14417776, 14541649), ovary (Hyseq clone identification numbers 7634122, 8319153, 8494602, 8265358, 8375786), lung tumor (Hyseq clone identification numbers 11047146, 7760706, 7774431, 9236436, 10280328, 11000820), leukocytes (Hyseq clone identification numbers 2251685 and 2357232), adult lung (Hyseq clone identification number 3394875), adrenal gland (Hyseq clone identification number 14066103), fetal lung (Hyseq clone identification numbers 15521916 and 11902971), thyroid gland (Hyseq clone identification number 10080227), fetal skin (Hyseq clone identification numbers 17941214, 18028270, 18060622, 18189205, 20576265), small intestine (Hyseq clone identification numbers 18431269 and 18356960), fetal muscle (Hyseq clone identification number 20887519), fetal kidney (Hyseq clone identification number 21990692), spinal cord (Hyseq clone identification numbers 9923443 and 10102150), thymus (Hyseq clone identification number 14992102), fetal brain (Hyseq clone identification number 15266959), cervix (Hyseq clone identification numbers 14029194, 14244274, 10022437), fetal heart (Hyseq clone identification number 21913716), umbilical cord (Hyseq clone identification number 18568149), lymphocyte (Hyseq clone identification number 10257378), lung fibroblast (Hyseq clone identification number 17116257).
The compositions of the present invention additionally include vectors, including expression vectors, containing the polynucleotides of the invention, cells genetically engineered to contain such polynucleotides and cells genetically engineered to express such polynucleotides.
The isolated polynucleotides of the invention include, but are not limited to, a polynucleotide comprising any one of the nucleotide sequences set forth in the SEQ ID NO: 1-22 and SEQ ID NO: 24; a polynucleotide comprising any of the full length protein coding sequences of the SEQ ID NO: 1-22 and SEQ ID NO: 24; and a polynucleotide comprising any of the nucleotide sequences of the mature protein coding sequences of the SEQ ID NO: 1-22 and SEQ ID NO: 24. The polynucleotides of the present invention also include, but are not limited to, a polynucleotide that hybridizes under stringent hybridization conditions to (a) the complement of any one of the nucleotide sequences set forth in the SEQ ID NO: 1-22 and SEQ ID NO: 24; (b) a nucleotide sequence encoding any one of SEQ ID NO: 23 or 25 or the amino acid sequences set forth in Table A; a polynucleotide which is an allelic variant of any polynucleotides recited above; a polynucleotide which encodes a species homolog (e.g. orthologs) of any of the proteins recited above; or a polynucleotide that encodes a polypeptide comprising a specific domain or truncation of any of the polypeptides comprising SEQ ID NO: 23 or 25 or set forth in Table A.
The nucleic acid sequences of the present invention also include the sequence information from the nucleic acid sequences of SEQ ID NO: 1-22 and SEQ ID NO: 24. The sequence information can be a segment of any one of SEQ ID NO: 1-22 and SEQ ID NO: 24 that uniquely identifies or represents the sequence information of SEQ ID NO: 1-22 and SEQ ID NO: 24. One such segment can be a twenty-mer nucleic acid sequence because the probability that a twenty-mer is fully matched in the human genome is 1 in 300. In the human genome, there are three billion base pairs in one set of chromosomes. Because 4
20
possible twenty-mers exist, there are 300 times more twenty-mers than there are base pairs in a set of human chromosome. Using the same analysis, the probability for a seventeen-mer to be fully matched in the human genome is approximately 1 in 5. When these segments are used in arrays for expression studies, fifteen-mer segment can be used. The probability that the fifteen-mer is fully matched in the expressed sequences is also approximately one in five because expressed sequences in one tissue comprise approximately 5% of the entire genome sequence.
Similarly, when using a sequence information for

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