Compositions and methods for the inhibition of phagocytes
AssigneeResearch Corporation Technologies, Inc.
InventorJ. Allen D. Cooper, Jr.
Life of this patent
Estimating the term…
Abstract
The present invention relates to the identification, purification and characterization of novel factors which inhibit phagocyte activation, such as inhibiting polymorphonuclear neutrophil chemotaxis, degranulation and superoxide production. Disclosed are natural peptides purified from the bronchial environment and a variety synthetic peptides and analogues designed to have enhanced or longer-lasting phagocyte-inhibiting activity. The peptides and compositions of the present invention are contemplated for use in modulating inflammatory responses in a number of clinical settings, such as in the treatment of asthma, bronchitis, acute lung injury, rheumatoid arthritis, psoriasis, dermatitis and inflammatory bowel disease, and for use as anti-proliferative agents such as in the treatment of cancer.
Claims38
A peptide of between five and about 100 amino acid residues in length including within its sequence an amino acid sequence comprising AA.sub.1 -AA.sub.2 -AA.sub.3 -Phe-Phe, wherein
- AA.sub.1 is glycine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, leucine, isoleucine, threonine, serine or tyrosine;
- AA.sub.2 is serine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, threonine, or tyrosine;
- AA.sub.3 is tyrosine, alanine, glycine, tryptophan, proline, histidine, asparagine, glutamine, cysteine, methionine, valine, phenylalanine, leucine, isoleucine, serine or threonine;
- when said peptide is 5 amino acids in length and AA.sub.2 is Ala, either AA.sub.1 is not Gly or AA.sub.3 is not Ala;
- and
- wherein said peptide lacks an N-Terminal Lys-Thr-Lys contiguous to AA.sub.1.
A peptide of between five and about 100 amino acid residues in length including within its sequence an amino acid sequence comprising AA.sub.1 -AA.sub.2 -AA.sub.3 -Phe-Phe, wherein
- AA.sub.1 is glycine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, leucine, isoleucine, threonine, serine or tyrosine;
- AA.sub.2 is serine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, threonine, or tyrosine;
- AA.sub.3 is tyrosine, alanine, glycine, tryptophan, proline, histidine, asparagine, glutamine, cysteine, methionine, valine, phenylalanine, leucine, isoleucine, serine or threonine;
- when said peptide is 32 amino acids in length and AA.sub.2 is Ala, either AA.sub.1 or AA.sub.3 is not Gly;
- and wherein said peptide lacks an N-Terminal Lys-Thr-Lys contiguous to AA.sub.1.
A peptide of between five and about 100 amino acid residues in length including within its sequence an amino acid sequence comprising AA.sub.1 -AA.sub.2 -AA.sub.3 -Phe-Phe, wherein
- AA.sub.1 is glycine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, leucine, isoleucine, threonine, serine or tyrosine;
- AA.sub.2 is serine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, threonine, or tyrosine;
- AA.sub.3 is tyrosine, alanine, glycine, tryptophan, proline, histidine, asparagine, glutamine, cysteine, methionine, valine, phenylalanine, leucine, isoleucine, serine or threonine;
- when said peptide is 10 amino acids in length and AA.sub.2 is Ser, either AA.sub.1 or AA.sub.3 is not Gly;
- and wherein said peptide lacks an N-Terminal Lys-Thr-Lys contiguous to AA.sub.1.
A peptide of between 5 and about 100 amino acid residues in length comprising the amino acid sequence Gly-Ser-Tyr-Phe-Phe (SEQ ID NO:3).
A peptide of between 5 and about 100 amino acid residues in length comprising the amino acid sequence Gly-Ser-Ala-Phe-Phe (SEQ ID NO:13).
A peptide of between 5 and about 100 amino acid residues in length comprising the amino acid sequence Gly-Ala-Tyr-Phe-Phe (SEQ ID NO:14).
A peptide of between 5 and about 100 amino acid residues in length comprising the amino acid sequence Arg-Glu-Gly-Ser-Tyr-Phe-Phe-Gly-Asp-Asn-Ala (SEQ ID NO:1).
A composition which comprises a peptide of between five and about 100 amino acid residues in length including within its sequence an amino acid sequence comprising AA.sub.1 -AA.sub.2 -AA.sub.3 -Phe-Phe, when
- (a) AA.sub.1 is glycine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, leucine, isoleucine, threonine, serine or tyrosine;
- (b) AA.sub.2 is serine, alanine, glycine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, threonine or tyrosine;
- (c) AA.sub.3 is tyrosine, alanine, glycine, tryptophan, proline, histidine, asparagine, glutamine, cysteine, methionine, valine, phenylalanine, leucine, isoleucine, serine or threonine;
- wherein said peptide lacks an N-Terminal Lys-Thr-Lys contiguous to AA.sub.1 ;
- and
- a pharmaceutically acceptable carrier.
A peptide of between 5 and about 100 amino acid residues in length comprising AA.sub.1 -AA.sub.2 -AA.sub.3 -Phe-Phe, wherein:
- AA.sub.1 is glycine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, leucine, isoleucine, threonine, serine or tyrosine;
- AA.sub.2 is serine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, threonine, or tyrosine;
- AA.sub.3 is tyrosine, alanine, glycine, tryptophan, proline, histidine, asparagine, glutamine, cysteine, methionine, valine, phenylalanine, leucine, isoleucine, serine, or threonine;
- wherein said peptide lacks an N-Terminal Lys-Thr-Lys contiguous to AA.sub.1 ;
- and wherein said peptide is biologically protected.
A peptide of between five and about 100 amino acid residues in length comprising AA.sub.1 -AA.sub.2 -AA.sub.3 -Phe-Phe, wherein
- AA.sub.1 is glycine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, leucine, isoleucine, threonine, serine or tyrosine;
- AA.sub.2 is serine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, threonine, or tyrosine;
- AA.sub.3 is tyrosine, alanine, glycine, tryptophan, proline, histidine, asparagine, glutamine, cysteine, methionine, valine, phenylalanine, leucine, isoleucine, serine or threonine;
- when said peptide is 8 amino acids in length and AA.sub.2 is Ala, either AA.sub.1 is not Gly or AA.sub.3 is not Ala;
- and
- wherein said peptide lacks an N-Terminal Lys-Thr-Lys contiguous to AA.sub.1.
A peptide of between five and about 100 amino acid residues in length comprising AA.sub.1 -AA.sub.2 -AA.sub.3 -Phe-Phe, wherein
- AA.sub.1 is glycine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, leucine, isoleucine, threonine, serine or tyrosine;
- AA.sub.2 is serine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, threonine, or tyrosine;
- AA.sub.3 is tyrosine, alanine, glycine, tryptophan, proline, histidine, asparagine, glutamine, cysteine, methionine, valine, phenylalanine, leucine, isoleucine, serine or threonine;
- when said peptide is 9 amino acids in length and AA.sub.2 is Ala, either AA.sub.1 is not Gly or AA.sub.3 is not Ala;
- and
- wherein said peptide lacks an N-Terminal Lys-Thr-Lys contiguous to AA.sub.1.
A peptide of between five and about 100 amino acid residues in length comprising AA.sub.1 -AA.sub.2 -AA.sub.3 -Phe-Phe, wherein
- AA.sub.1 is glycine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, leucine, isoleucine, threonine, serine or tyrosine;
- AA.sub.2 is serine, alanine, tryptophan, proline, asparagine, glutamine, histidine, cysteine, methionine, valine, threonine, or tyrosine;
- AA.sub.3 is tyrosine, alanine, glycine, tryptophan, proline, histidine, asparagine, glutamine, cysteine, methionine, valine, phenylalanine, leucine, isoleucine, serine or threonine;
- when said peptide is 12 amino acids in length and AA.sub.2 is Ala, either AA.sub.1 is not Gly or AA.sub.3 is not Ala;
- and
- wherein said peptide lacks an N-Terminal Lys-Thr-Lys contiguous to AA.sub.1 .
Dependencies are inferred from the claim text.