Treatment of ophthalmic conditions with angiopoietin-like 7 (ANGPTL7) inhibitors

Patent metadata

Field	Value
Publication number	US-11845989-B2
Application number	US-202017031523-A
Country	US
Kind code	B2
Filing date	Sep 24, 2020
Priority date	Jan 23, 2019
Publication date	Dec 19, 2023
Grant date	Dec 19, 2023

Abstract

The present disclosure provides methods of treating patients having an ophthalmic condition, methods of identifying subjects having an increased risk of developing an ophthalmic condition, methods of detecting human angiopoietin like 7 (ANGPTL7) variant nucleic acid molecules and variant polypeptides, and ANGPTL7 variant nucleic acid molecules and variant polypeptides.

First claim

What is claimed is:

1. A method of treating a patient having glaucoma or increased intraocular pressure (TOP), the method comprising administering an angiopoietin like 7 (ANGPTL7) inhibitor to the patient, wherein the ANGPTL7 inhibitor comprises an antisense molecule that hybridizes to a sequence within an ANGPTL7 mRNA or an ANGPTL7 genomic nucleic acid molecule and decreases expression of the ANGPTL7 polypeptide in a cell in the patient.

2. The method according to claim 1 , wherein the antisense molecule comprises an antisense nucleic acid molecule, a small interfering RNA (siRNA), or a short hairpin RNA (shRNA) that hybridizes to an ANGPTL7 mRNA.

3. The method according to claim 1 , further comprising detecting the presence or absence of an ANGPTL7 predicted loss-of-function variant nucleic acid molecule encoding ANGPTL7 Gln175His, ANGPTL7 Arg177Stop, ANGPTL7 Trp188Stop, ANGPTL7 Lys192Gln, ANGPTL7 Phe161Ile, ANGPTL7 Arg340His, ANGPTL7 Arg220His, ANGPTL7 Asn302Lys, or ANGPTL7 Arg220Cys in a biological sample from the patient;
wherein when the patient is ANGPTL7 reference, the patient is also administered a therapeutic agent that treats or inhibits glaucoma or TOP in a standard dosage amount, and when the patient is heterozygous for an ANGPTL7 predicted loss-of-function variant, the patient is also administered a therapeutic agent that treats or inhibits glaucoma or TOP in a dosage amount that is the same as or lower than the standard dosage amount.

4. The method according to claim 3 , wherein the ANGPTL7 predicted loss-of-function variant nucleic acid molecule is:
a genomic nucleic acid molecule having a nucleotide sequence comprising a thymine at a position corresponding to position 4,291 according to SEQ ID NO:2, a genomic nucleic acid molecule having a nucleotide sequence comprising a thymine at a position corresponding to position 4,287 according to SEQ ID NO:3, a genomic nucleic acid molecule having a nucleotide sequence comprising an adenine at a position corresponding to position 4,243 according to SEQ ID NO:132, a genomic nucleic acid molecule having a nucleotide sequence comprising an adenine at a position corresponding to position 4,325 according to SEQ ID NO:133, or a genomic nucleic acid molecule having a nucleotide sequence comprising a cytosine at a position corresponding to position 4,336 according to SEQ ID NO:134;
an mRNA molecule having a nucleotide sequence comprising a uracil at a position corresponding to position 529 according to SEQ ID NO:5, an mRNA molecule having a nucleotide sequence comprising a uracil at a position corresponding to position 525 according to SEQ ID NO:6, an mRNA molecule having a nucleotide sequence comprising an adenine at a position corresponding to position 481 according to SEQ ID NO:135, an mRNA molecule having a nucleotide sequence comprising an adenine at a position corresponding to position 563 according to SEQ ID NO:136, or an mRNA molecule having a nucleotide sequence comprising a cytosine at a position corresponding to position 574 according to SEQ ID NO:137; or
a cDNA molecule produced from an mRNA molecule, wherein the cDNA molecule has a nucleotide sequence comprising a thymine at a position corresponding to position 529 according to SEQ ID NO:8, a cDNA molecule produced from an mRNA molecule, wherein the cDNA molecule has a nucleotide sequence comprising a thymine at a position corresponding to position 525 according to SEQ ID NO:9, a cDNA molecule produced from an mRNA molecule, wherein the cDNA molecule has a nucleotide sequence comprising an adenine at a position corresponding to position 481 according to SEQ ID NO:138, a cDNA molecule produced from an mRNA molecule, wherein the cDNA molecule has a nucleotide sequence comprising an adenine at a position corresponding to position 563 according to SEQ ID NO:139, or a cDNA molecule produced from an mRNA molecule, wherein the cDNA molecule has a nucleotide sequence comprising a cytosine at a position corresponding to position 574 according to SEQ ID NO:140.

Assignees

• Regeneron Pharma

Inventors

• Praveen Kavita
• Schurmann Claudia
• Gurski Lauren
• Teslovich Dostal Tanya
• Abecasis Goncalo
• Baras Aris
• Coppola Giovanni
• Patel Gaurang
• Hu Ying
• Romano Carmelo
• Della Gatta Giusy
• Persaud Trikaldarshi

Classifications

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• C12N15/1096

  cDNA Synthesis; Subtracted cDNA library construction, e.g. RT, RT-PCR · CPC title

• C12N15/111

  General methods applicable to biologically active non-coding nucleic acids · CPC title