Compositions and methods for design of non-immunogenic proteins
First Claim
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1. A library of sequences of peptide motifs found in human proteins, comprising a set of all sequences of human peptides having more than 4 amino acid residues, and less than about 50 amino acid residues.
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Abstract
Provided are methods for de novo design of proteins that are non-immunogenic when administered for therapeutic purposes. The methods involve protein design based on combinations of peptide fragments naturally encountered by the immune system.
15 Citations
21 Claims
- 1. A library of sequences of peptide motifs found in human proteins, comprising a set of all sequences of human peptides having more than 4 amino acid residues, and less than about 50 amino acid residues.
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6. A library of sequences of peptide motifs found in human proteins, wherein the human proteins are members of a distinct class of molecules, said class defined by a structural motif or function.
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7. A library comprising isolated polynucleotides encoding a set of all human peptide sequences having more than 4 amino acid residues, and less than about 50 amino acid residues.
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8. A library comprising polynucleotides encoding peptide motifs found in human proteins, wherein the human proteins are members of a distinct class of molecules, said class defined by a structural motif or a function.
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9. A method of designing a novel protein comprising:
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(a) selecting a scaffold protein;
(b) identifying a partial structure of the scaffold protein to be replaced;
(c) computationally searching and identifying a human peptide, wherein the human peptide;
(i) is a member of a library comprising a set of all sequences of human peptides having more than 4 amino acid residues and less than about 50 amino acid residues; and
(ii) shares a structural motif with the partial structure of the scaffold protein;
(d) replacing a portion of the amino acid sequence of the scaffold protein corresponding to the partial structure with the amino acid sequence of the human peptide to produce a novel protein; and
(e) optimizing the structure of the novel protein to retain the structural motif.
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10. A method of producing a novel protein, comprising:
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(a) selecting a scaffold protein;
(b) identifying a partial structure of the scaffold protein to be replaced;
(c) computationally searching and identifying one or more human peptides, wherein the human peptides;
(i) are a member of library comprising a set of all sequences of human peptides having more than 4 amino acid residues and less than about 50 amino acid residues; and
(ii) share a structural motif with the partial structure; and
(d) replacing the partial structure sequence with the sequence of a human peptide to create a sequence of the novel protein;
(e) creating a polynucleotide that encodes the amino acid sequence of the novel protein; and
(f) expressing the polynucleotide to produce the novel protein. - View Dependent Claims (11, 12, 14)
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13. A protein which is non-immunogenic to humans, wherein the protein comprises human peptide segments, which peptide segments are recognized as self by the human immune system, and wherein the protein does not naturally occur in humans.
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15. A pharmaceutical composition comprising:
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(a) an isolated and purified protein comprising human peptide segments, which peptide segments are recognized as self by the human immune system, and wherein the protein does not naturally occur in humans; and
(b) a pharmaceutically acceptable excipient.
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16. A method of designing a novel protein comprising:
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(a) selecting a scaffold protein;
(b) identifying a partial structure or disordered region of the scaffold protein to be replaced;
(c) computationally searching and identifying one or more human peptides, wherein the human peptides;
(i) are a member of a library comprising a set of all sequences of human peptides having more than 4 amino acid residues and less than about 50 amino acid residues; and
(ii) share a structural motif with the partial structure of the scaffold protein or are disordered;
(d) replacing a portion of the amino acid sequence of the scaffold protein corresponding to the partial structure or disordered region with the amino acid sequence of a human peptide to produce a novel protein; and
(e) optimizing the structure of the novel protein to retain the overall structure of the scaffold protein. - View Dependent Claims (17, 18, 19, 20, 21)
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Specification