# US 7,745,579 B1 · Inhibitor of NF-KB activation

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- Number: US 7,745,579 B1
- Document ID: US7745579B1
- Status: Granted
- Kind: B1
- Application number: 09/671,687
- Filed: 2000-09-28
- Granted: 2010-06-29
- Earliest claimed: 1998-09-01
- Inventors: David Wallach; Andrei Kovalenko; Giuseppina Cantarella
- Web page: https://patentgrep.com/patent/US7745579B1

## CPC

- C07K 14/4703: {Inhibitors; Suppressors}
- 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 present invention relates to a protein, designated NAP (Nemo Associated Protein), that was discovered to inhibit the activation of transcription factor NF-kB by various signals that are important in inflammatory and immune processes. The DNA and the recombinant production of this protein is also disclosed as well as methods of using the protein or encoding DNA.

## Claims

### Claim 1

An isolated protein which is capable of binding to tumor necrosis factor receptor-associated 2 protein (TRAF2), said protein comprising:
(A) a polypeptide of SEQ ID NO:3; or
(B) a variant that has no more than ten amino acid changes from the amino acid sequence of SEQ ID NO:3, wherein said variant is capable of binding to TRAF2.

### Claim 2 (depends on 1)

The isolated protein of claim 1, which is a protein comprising the amino acid sequence of SEQ ID NO:3.

### Claim 3 (depends on 1)

A composition comprising the isolated protein of claim 1 and a pharmaceutically acceptable excipient, diluent, or auxiliary agent.

### Claim 4 (depends on 1)

A molecule having the binding portion of an antibody capable of binding to the portion of said isolated protein of claim 1 that is said polypeptide of (A) or said variant of (B).

### Claim 5 (depends on 4)

The molecule of claim 4, which is an antibody.

### Claim 6 (depends on 5)

The molecule of claim 5, wherein said antibody is a monoclonal antibody.

### Claim 7 (depends on 4)

A composition comprising the molecule of claim 4, and a pharmaceutically acceptable excipient, diluent, or auxiliary agent.

### Claim 8 (depends on 1)

An isolated protein in accordance with claim 1, wherein said protein and said variant are each capable of binding to a component of the NF-κB complex selected from the group consisting of IKappaB kinase complex associated protein (IKAP), IKappaB kinase-alpha (IKK-alpha), IKappaB kinase-beta (IKK-beta), IKappaB kinase-gamma (IKK-gamma) and NF-κB inducing kinase (NIK).

### Claim 9 (depends on 1)

An isolated protein in accordance with claim 1, comprising a variant of the polypeptide of SEQ ID NO:3, which variant has no more than ten amino acid changes from the amino acid sequence of SEQ ID NO:3, and which variant is capable of binding to TRAF2.

### Claim 10 (depends on 1)

The isolated protein of claim 1, wherein said variant of (B) has no more than five amino acid changes from the amino acid sequence of SEQ ID NO:3.

### Claim 11 (depends on 1)

The isolated protein of claim 1, wherein each said change from the amino acid sequence of SEQ ID NO:3 is a conservative substitution selected from among the substitutions in the following list:
Original
Residue
Substitution
Ala
Gly; Ser
Arg
Lys
Asn
Gln; His
Asp
Glu
Cys
Ser
Gln
Asn
Glu
Asp
Gly
Ala; Pro
His
Asn; Gln
Ile
Leu; Val
Leu
Ile; Val
Lys
Arg; Gln; Glu
Met
Leu; Tyr; Ile
Phe
Met; Leu; Tyr
Ser
Thr
Thr
Ser
Trp
Tyr
Tyr
Trp; Phe
Val
Ile; Leu
or a conservative substitution that is an exchange within one of the following five groups:
Small aliphatic, nonpolar or
slightly polar residues:
Ala, Ser, Thr, Pro, Gly;
Polar negatively charged
Asp, Asn, Glu, Gln;
residues and their amides:
Polar, positively oharged residues:
His, Arg, Lys;
Large aliphatic nonpolar residues:
Met, Leu, Ile, Val, Cys;
and
Large aromatic residues:
Phe, Tyr, Trp.

### Claim 12 (depends on 11)

The isolated protein of claim 11, wherein said variant has no more than 5 of said amino acid changes from the amino acid sequence of SEQ ID NO:3.

### Claim 13

A molecule having the binding portion of an antibody capable of binding to the polypeptide of SEQ ID NO:3.

### Claim 14 (depends on 13)

The molecule of claim 13, which is an antibody.

### Claim 15 (depends on 14)

The molecule of claim 14, wherein said antibody is a monoclonal antibody.

### Claim 16

An isolated protein comprising:
A) a polypeptide of SEQ ID NO: 3; or
B) a variant that has no more than 10 amino acid changes from the amino acid sequence of SEQ ID NO:3.

### Claim 17 (depends on 16)

The isolated protein of claim 16, wherein said variant has no more than 5 of said amino acid changes from the amino acid sequence of SEQ ID NO:3.