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Title:  18891, a novel human lipase

United States Patent:  6,337,187

Inventors:  Kapeller-Libermann; Rosana (Chestnut Hill, MA)

Assignee:  Millennium Pharmaceuticals, Inc. (Cambridge, MA)

Appl. No.:  434613

Filed:  November 5, 1999

Abstract

The present invention relates to a newly identified human lipase belonging to the family of mammalian lipases. The invention also relates to polynucleotides encoding the lipase. The invention further relates to methods using the lipase polypeptides and polynucleotides as a target for diagnosis and treatment in lipase-mediated or -related disorders. The invention further relates to drug-screening methods using the lipase polypeptides and polynucleotides to identify agonists and antagonists for diagnosis and treatment. The invention further encompasses agonists and antagonists based on the lipase polypeptides and polynucleotides. The invention further relates to procedures for producing the lipase polypeptides and polynucleotides.

SUMMARY OF THE INVENTION

It is an object of the invention to identify novel lipases.

It is a further object of the invention to provide novel lipase polypeptides that are useful as reagents or targets in assays applicable to treatment and diagnosis of lipase-mediated or -related disorders, especially disorders mediated by or related to lipase enzymes.

It is a further object of the invention to provide polynucleotides corresponding to the novel lipase polypeptides that are useful as targets and reagents in assays applicable to treatment and diagnosis of lipase or lipase-mediated or -related disorders and useful for producing novel lipase polypeptides by recombinant methods.

A specific object of the invention is to identify compounds that act as agonists and antagonists and modulate the expression of the novel lipase.

A further specific object of the invention is to provide compounds that modulate expression of the lipase for treatment and diagnosis of lipase and lipase-related disorders.

The invention is thus based on the identification of a novel human lipase. The amino acid sequence is shown in SEQ ID NO 1. The nucleotide sequence is shown in SEQ ID NO 2.

The invention provides isolated lipase polypeptides, including a polypeptide having the amino acid sequence shown in SEQ ID NO:1 or the amino acid sequence encoded by the cDNA deposited as ATCC Patent Deposit No. PTA-1915 May 24,2000 ("the deposited cDNA").

The invention also provides isolated lipase nucleic acid molecules having the sequence shown in SEQ ID NO 2 or in the deposited cDNA.

The invention also provides variant polypeptides having an amino acid sequence that is substantially homologous to the amino acid sequence shown in SEQ ID NO 1 or encoded by the deposited cDNA.

The invention also provides variant nucleic acid sequences that are substantially homologous to the nucleotide sequence shown in SEQ ID NO 2 or in the deposited cDNA.

The invention also provides fragments of the polypeptide shown in SEQ ID NO 1 and nucleotide sequence shown in SEQ ID NO 2, as well as substantially homologous fragments of the polypeptide or nucleic acid.

The invention further provides nucleic acid constructs comprising the nucleic acid molecules described herein. In a preferred embodiment, the nucleic acid molecules of the invention are operatively linked to a regulatory sequence.

The invention also provides vectors and host cells for expressing the lipase nucleic acid molecules and polypeptides, and particularly recombinant vectors and host cells.

The invention also provides methods of making the vectors and host cells and methods for using them to produce the lipase nucleic acid molecules and polypeptides.

The invention also provides antibodies or antigen-binding fragments thereof that selectively bind the lipase polypeptides and fragments.

The invention also provides methods of screening for compounds that modulate expression or activity of the lipase polypeptides or nucleic acid (RNA or DNA).

The invention also provides a process for modulating lipase polypeptide or nucleic acid expression or activity, especially using the screened compounds. Modulation may be used to treat conditions related to aberrant activity or expression of the lipase polypeptides or nucleic acids or aberrant activity resulting in the altered accumulation/degradation of lipids.

The invention also provides assays for determining the activity of or the presence or absence of the lipase polypeptides or nucleic acid molecules in a biological sample, including for disease diagnosis.

The invention also provides assays for determining the presence of a mutation in the polypeptides or nucleic acid molecules, including for disease diagnosis.

In still a further embodiment, the invention provides a computer readable means containing the nucleotide and/or amino acid sequences of the nucleic acids and polypeptides of the invention, respectively.

Claim 1 of 13 Claims

That which is claimed:

1. An isolated nucleic acid molecule having a nucleotide sequence selected from the group consisting of:

(a) the nucleotide sequence shown in SEQ ID NO:2;

(b) the nucleotide sequence of the cDNA insat contained in ATCC Deposit No. PTA-1915;

(c) a nucleotide sequence encoding the amino acid sequence shown in SEQ ID NO:1;

(d) a nucleotide sequence encoding the amino acid sequence encoded by the cDNA insert contained in ATCC Deposit No. PTA-1915; and

(e) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), or (d).

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If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.

 

 

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