# US 6,852,693 B2 · Compositions and methods for promoting lipid mobilization in humans

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 6,852,693 B2
- Document ID: US6852693B2
- Status: Granted
- Kind: B2
- Application number: 10/072,419
- Filed: 2002-02-07
- Published: 2003-08-28
- Granted: 2005-02-08
- Earliest claimed: 2002-02-07
- Assignees: BLM Group
- Inventors: Bernice Schacter; Lee P. Schacter
- Web page: https://patentgrep.com/patent/US6852693B2

## CPC

- G01N 33/5038: {involving detection of metabolites per se}
- A61K 38/1767: {from invertebrates}
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 7/06: having 5 to 11 amino acids
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- G01N 33/5044: {involving specific cell types}
- G01N 33/5061: {Muscle cells}
- G01N 33/5067: {Liver cells}
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The invention provides methods of using polypeptide compounds based on the structures of insect peptides of the adipokinetic hormone family to mobilize lipids in humans. The compositions and methods described in the application are useful for modulating human body weight, such as inducing weight loss. The invention also includes screening methods for identifying other compounds effective for modulating lipid mobilization in humans.

## Claims

### Claim 1

A method of promoting lipid mobilization in a human, the method comprising administering an insect adipokinetic hormone to the human in an amount effective to mobilize lipids in the human.

### Claim 2 (depends on 1)

The method of claim 1, wherein the hormone has a molecular weight less than 2500.

### Claim 3 (depends on 1)

The method of claim 1, wherein the hormone is a polypeptide having a pyroglutamate residue at its amino terminus.

### Claim 4 (depends on 1)

The method of claim 1, wherein the hormone is a polypeptide having a blocked carboxyl terminus.

### Claim 5 (depends on 4)

The method of claim 4, wherein the carboxyl terminus of the polypeptide is amidated.

### Claim 6 (depends on 1)

The method of claim 1, wherein the hormone is a polypeptide that does not have internal disulfide bonds.

### Claim 7 (depends on 1)

The method of claim 1, wherein the hormone is characterized in that its ability to promote lipid mobilization is not significantly inhibited by propanolol.

### Claim 8 (depends on 1)

The method of claim 1, wherein the hormone is a polypeptide characterized in that:
i) it has a molecular weight less than 2500;
ii) it has a pyroglutamate residue at its amino terminus;
iii) it is amidated at its carboxyl terminus;
iv) it does not have internal disulfide bonds; and
v) its ability to promote lipid mobilization is not significantly inhibited by propanolol.

### Claim 9 (depends on 1)

The method of claim 1, wherein the hormone has the chemical structure
Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-X-Z,
wherein:
Xaa1 is a pyroglutamate residue;
Xaa2 is one of a leucine residue, an isoleucine residue, a valine residue, a phenylalanine residue, and a tyrosine residue;
Xaa3 is one of an asparagine residue and a threonine residue;
Xaa4 is one of a phenylalanine residue and a tyrosine residue;
Xaa5 is one of a threonine residue and a serine residue;
Xaa6 is one of a proline residue, a serine residue, a threonine residue, and an alanine residue;
Xaa7 is one of a glycine residue, an asparagine residue, a serine residue, an aspartate residue, a valine residue, and a tryptophan residue;
Xaa8 is a tryptophan residue;
X is from 0 to 10 amino acid residues; and
Z is one of a hydrogen radical and a carboxyl terminus-blocking moiety.

### Claim 10 (depends on 9)

The method of claim 9, wherein:
Xaa2 is one of a leucine residue and a valine residue;
Xaa6 is one of a proline residue, a serine residue, and a threonine residue;
Xaa7 is one of a glycine residue, an asparagine residue, and a serine residue;
Xaa8 is a tryptophan residue;
X is from 0 to 3 amino acid residues; and
Z is an (—NH2) radical.

### Claim 11 (depends on 10)

The method of claim 10, wherein Xaa4 is a phenylalanine residue.

### Claim 12 (depends on 9)

The method of claim 9, wherein:
X is 0 amino acid residues; and
Z is an (—NH2) radical.

### Claim 13 (depends on 9)

The method of claim 9, wherein X is a glycine residue.

### Claim 14 (depends on 13)

The method of claim 13, wherein Z is an (—NH2) radical.

### Claim 15 (depends on 9)

The method of claim 9, wherein X has the chemical structure
Xaa9-Xaa10
wherein:
Xaa9 is a glycine residue; and
Xaa10 is one of a threonine residue, a glycine residue, a tryptophan residue, a serine residue, and an asparagine residue.

### Claim 16 (depends on 15)

The method of claim 15, wherein Xaa10 a threonine residue.

### Claim 17 (depends on 15)

The method of claim 15, wherein Z is an (—NH2) radical.

### Claim 18 (depends on 9)

The method of claim 9, wherein X has the chemical structure
Xaa9-Xaa10-Xaa11
wherein:
Xaa9 is a glycine residue;
Xaa10 is one of a threonine residue, a glycine residue, a tryptophan residue, a serine residue, and an asparagine residue; and
Xaa11 is a lysine residue.

### Claim 19 (depends on 9)

The method of claim 9, wherein X has the chemical structure
Xaa9-Xaa10-Xaa11-(Xaa12)n
wherein
n is from 0 to 7
Xaa9 is a glycine residue,
Xaa10, when present, is one of a threonine residue, a glycine residue, a tryptophan residue, a serine residue, and an asparagine residue;
Xaa11, when present, is a lysine residue; and
each Xaa12, when present, is any amino acid residue.

### Claim 20 (depends on 9)

The method of claim 9, wherein X is a glycine residue and Z is a hydrogen radical.

### Claim 21 (depends on 9)

The method of claim 9, wherein the hormone is administered in an amount in the range from 100 milligrams to about 2 grams per day.

### Claim 22 (depends on 21)

The method of claim 21, wherein the hormone is administered in an amount in the range from 200 milligrams to 1.0 gram per day.

### Claim 23 (depends on 1)

The method of claim 1, wherein the hormone has the chemical structure
Xaa1-Xaa22-Xaa23-Xaa24-Xaa25-Xaa26-Xaa27-Xaa28-X-Z,
wherein:
Xaa1 is a pyroglutamate residue;
Xaa22 is an amino acid residue having a non-polar side chain;
Xaa23 is an amino acid residue having a non-ionic polar side chain;
Xaa24 is an amino acid residue having an aromatic side chain;
Xaa25 is an amino acid residue having a non-ionic polar side chain;
Xaa26 is any amino acid residue;
Xaa27 is any amino acid residue;
Xaa28 is an amino acid residue having an aromatic side chain;
X is from 0 to 10 amino acid residues; and
Z is one of a hydrogen radical and a carboxyl terminus-blocking moiety.

### Claim 24 (depends on 23)

The method of claim 23, wherein:
Xaa26 is one of a proline residue, a serine residue, a threonine residue, and an alanine residue.

### Claim 25 (depends on 23)

The method of claim 23, wherein:
Xaa27 is one of a glycine residue, an asparagine residue, a serine residue, a glutamate residue, a valine residue, and a tryptophan residue.

### Claim 26 (depends on 23)

The method of claim 23, wherein Z is an (—NH2) radical.

### Claim 27 (depends on 26)

The method of claim 26, wherein X is 0 amino acid residues.

### Claim 28 (depends on 23)

The method of claim 23, wherein X is a glycine residue and Z is a hydrogen radical.

### Claim 29

A method of promoting lipid mobilization in a human, the method comprising administering to the human, in an amount effective to mobilize lipids in the human, a compound having the chemical structure
Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-X-Z,
wherein:
Xaa1 is a pyroglutamate residue;
Xaa2 is one of a leucine residue, an isoleucine residue, a valine residue, a phenylalanine residue, and a tyrosine residue;
Xaa3 is one of an asparagine residue and a threonine residue;
Xaa4 is one of a phenylalanine residue and a tyrosine residue;
Xaa5 is one of a threonine residue and a seine residue;
Xaa6 is one of a proline residue, a serine residue, a threonine residue, and an alanine residue;
Xaa7 is one of a glycine residue, an asparagine residue, a seine residue, an aspartate residue, a valine residue, and a tryptophan residue;
Xaa8 is a tryptophan residue;
X is from 0 to 10 amino acid residues; and
Z is one of a hydrogen radical and a carboxyl terminus-blocking moiety.

### Claim 30

A method of promoting lipid mobilization in a human, the method comprising administering to the human, in an amount effective to mobilize lipids in the human, a compound having the chemical structure
Xaa1-Xaa22-Xaa23-Xaa24-Xaa25-Xaa26-Xaa27-Xaa28-X-Z,
wherein:
Xaa1 is a pyroglutamate residue;
Xaa22 is an amino acid residue having a non-polar side chain;
Xaa23 is an amino acid residue having a non-ionic polar side chain;
Xaa24 is an amino acid residue having an aromatic side chain;
Xaa25 is an amino acid residue having a non-ionic polar side chain;
Xaa26 is any amino acid residue;
Xaa27 is any amino acid residue;
Xaa28 is an amino acid residue having an aromatic side chain;
X is from 0 to 10 amino acid residues; and
Z is one of a hydrogen radical and a carboxyl terminus-blocking moiety.

### Claim 31

A method of promoting weight loss in a human, the method comprising administering an insect adipokinetic hormone to the human in an amount effective to mobilize lipids in the human.

### Claim 32 (depends on 11)

The method of claim 11, wherein the human is afflicted with obesity.

### Claim 33

A method of suppressing the appetite of a human, the method comprising administering an insect adipokinetic hormone to the human in an amount effective to mobilize lipids in the human, whereby the human's appetite is suppressed.

### Claim 34

A method of promoting lipid mobilization in a human, the method comprising administering an insect adipokinetic hormone to the human in an amount effective to mobilize lipids in the human, wherein the hormone has the chemical structure
Xaa1-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Z,
wherein:
Xaa1 is a pyroglutamate residue;
Xaa3 is one of an asparagine residue and a threonine residue;
Xaa4 is one of a phenylalanine residue and a tyrosine residue;
Xaa5 is one of a threonine residue and a serine residue;
Xaa6 is one of a proline residue, a serine residue, a threonine residue, and an alanine residue;
Xaa7 is one of a glycine residue, an asparagine residue, a serine residue, an aspartate residue, a valine residue, and a tryptophan residue;
Xaa8 is a tryptophan residue; and
Z is one of a hydrogen radical and a carboxyl terminus-blocking moiety.

### Claim 35

A method of promoting lipid mobilization in a human, the method comprising administering an insect adipokinetic hormone to the human in an amount effective to mobilize lipids in the human, wherein the hormone has the chemical structure
Xaa1-Xaa3-Xaa4 -Xaa5-Xaa6-Lys-Z,
wherein:
Xaa1 is a pyroglutamate residue;
Xaa3 is one of an asparagine residue and a threonine residue;
Xaa4 is one of a phenylalanine residue and a tyrosine residue;
Xaa5 is one of a threonine residue and a seine residue;
Xaa6 is one of a proline residue, a serine residue, a threonine residue, and an alanine residue; and
Z is one of a hydrogen radical and a carboxyl terminus-blocking moiety.

### Claim 36 (depends on 1)

The method of claim 1, wherein the hormone is a polypeptide having the amino acid sequence SEQ ID NO: 4.

### Claim 37 (depends on 31)

The method of claim 31, wherein the hormone is a polypeptide having the amino acid sequence SEQ ID NO: 4.

### Claim 38 (depends on 29)

The method of claim 29, wherein the compound is a polypeptide having the amino acid sequence SEQ ID NO: 4.

### Claim 39 (depends on 30)

The method of claim 30, wherein the compound is a polypeptide having the amino acid sequence SEQ ID NO: 4.

### Claim 40 (depends on 1)

The method of claim 1, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of locusts, bees, dragonflies, flies, butterflies, tobacco hornworm moths, beetles, grasshoppers, crickets, cockroaches, mantids, periodical cicadas, stick insects, firebugs, and corn ear worms.

### Claim 41 (depends on 1)

The method of claim 1, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of desert locusts, migratory locusts, honey bees, emperor dragonflies, damselflies, sawflies, fruit flies, horse flies, tenebrionid beetles, dung beetles, african pyrgomorphid grasshoppers, king crickets, ground crickets, american cockroaches, tropical cockroaches, and primitive cockroaches.

### Claim 42 (depends on 1)

The method of claim 1, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of Schistocera gregaria, Locusts migratoria, Apis mellifera, Libellula auripennis, Anax imperator, Pseudagrion inconspicuum, Ishnura senegalensis, Tenthredo arcuata, Drosophila melanogaster, Tabanus atratus, Phormia terraenova, Vanessa cardui, Manduca sexta, Melolontha melolontha, Geotrupes stercorosus, Tenebrio molitor, Zophobas rugipes, Phymateus leprosus, Melanoplus sanguinipes, Dictyophorus spumans, Phymateus morbillosus, Gryllodes sigillatus, Libanasidus vittatus, Heterodes namaqua, Acanthoproctus cervinus, Periplaneta americana, Leucophaea maderae, Gromphadorhina portenetosa, Blattella germanica, Blaberus discoidalis, Polyphaga aegyptiaca, Empusa pennata, Platypleura capensis, Cacama valavata, Diceroprocta semicinta, Extatosoma tiaratum, Pyrrhocoris apterus, and Heliothis zea.

### Claim 43 (depends on 1)

The method of claim 1, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of desert locusts, migratory locusts, honey bees, tobacco hornworm moths, grasshoppers, cockroaches, and corn ear worms.

### Claim 44 (depends on 1)

The method of claim 1, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of Schistocera gregaria, Locusta migratoria, Apis mellifera, Manduca sexta, Melanoplus sanguinipes, Gromphadorhina portenetosa, Blattella germanica, Blaberus discoidalis, and Heliothis zea.

### Claim 45 (depends on 31)

The method of claim 31, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of locusts, bees, dragonflies, flies, butterflies, tobacco hornworm moths, beetles, grasshoppers, crickets, cockroaches, mantids, periodical cicadas, stick insects, firebugs, and corn ear worms.

### Claim 46 (depends on 31)

The method of claim 31, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of desert locusts, migratory locusts, honey bees, emperor dragonflies, damselflies, sawflies, fruit flies, horse flies, tenebrionid beetles, dung beetles, african pyrgomorphid grasshoppers, king crickets, ground crickets, american cockroaches, tropical cockroaches, and primitive cockroaches.

### Claim 47 (depends on 31)

The method of claim 31, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of Schistocera gregaria, Locusta migratoria, Apis mellifera, Libellula auripennis, Anax imperator, Pseudagrion inconspicuum, Ishnura senegalensis, Tenthredo arcuata, Drosophila melanogaster, Tabanus atratus, Phormia terraenova, Vanessa cardui, Manduca sexta, Melolontha melolontha, Geotrupes stercorosus, Tenebrio molitor, Zophobas rugipes, Phymateus leprosus, Melanoplus sanguinipes, Dictyophorus spumans, Phymateus morbillosus, Gryllodes sigillatus, Libanasidus vittatus, Heterodes namaqua, Acanthoproctus cervinus, Periplaneta americana, Leucophaea maderae, Gromphadorhina portenetosa, Blattella germanica, Blaberus discoidalis, Polyphaga aegyptiaca, Empusa pennata, Platypleura capensis, Cacama valavata, Diceroprocta semicinta, Extatosoma tiaratum, Pyrrhocoris apterus, and Heliothis zea.

### Claim 48 (depends on 31)

The method of claim 31, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of desert locusts, migratory locusts, honey bees, tobacco hornworm moths, grasshoppers, cockroaches, and corn ear worms.

### Claim 49 (depends on 31)

The method of claim 31, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of Schistocera gregaria, Locusta migratoria, Apis mellifera, Manduca sexta, Melanoplus sanguinipes, Gromphadorhina portenetosa, Blattella germanica, Blaberus discoidalis, and Heliothis zea.

### Claim 50 (depends on 33)

The method of claim 33, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of locusts, bees, dragonflies, flies, butterflies, tobacco hornworm moths, beetles, grasshoppers, crickets, cockroaches, mantids, periodical cicadas, stick insects, firebugs, and corn ear worms.

### Claim 51 (depends on 33)

The method of claim 33, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of desert locusts, migratory locusts, honey bees, emperor dragonflies, damselflies, sawflies, fruit flies, horse flies, tenebrionid beetles, dung beetles, african pyrgomorphid grasshoppers, king crickets, ground crickets, american cockroaches, tropical cockroaches, and primitive cockroaches.

### Claim 52 (depends on 33)

The method of claim 33, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of Schistocera gregaria, Locusta migratoria, Apis mellifera, Libellula auripennis, Anax imperator, Pseudagrion inconspicuum, Ishnura senegalensis, Tenthredo arcuata, Drosophila melanogaster, Tabanus atratus, Phormia terraenova, Vanessa cardui, Manduca sexta, Melolontha melolontha, Geotrupes stercorosus, Tenebrio molitor, Zophobas rugipes, Phymateus leprosus, Melanoplus sanguinipes, Dictyophorus spumans, Phymateus morbillosus, Gryllodes sigillatus, Libanasidus vittatus, Heterodes namaqua, Acanthoproctus cervinus, Periplaneta americana, Leucophaea maderae, Gromphadorhina portenetosa, Blattella germanica, Blaberus discoidalis, Polyphaga aegyptiaca, Empusa pennata, Platypleura capensis, Cacama valavata, Diceroprocta semicinta, Extatosoma tiaratum, Pyrrhocoris apterus, and Heliothis zea.

### Claim 53 (depends on 33)

The method of claim 33, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of desert locusts, migratory locusts, honey bees, tobacco hornworm moths, grasshoppers, cockroaches, and corn ear worms.

### Claim 54 (depends on 33)

The method of claim 33, wherein the hormone is an adipokinetic hormone of an insect selected from the group consisting of Schistocera gregaria, Locusta migratoria, Apis mellifera, Manduca sexta, Melanoplus sanguinipes, Gromphadorhina portenetosa, Blattella germanica, Blaberus discoidalis, and Heliothis zea.