Compositions and methods for adjoining type I and type II extracellular domains as heterologous chimeric proteins
First Claim
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1. A heterologous chimeric protein comprising:
- (a) a first domain comprising a portion of PD-1 that is at least 95% identical to SEQ ID NO;
32 and is capable of binding a PD-1 ligand,(b) a second domain comprising a portion of OX-40 ligand (OX40L) that is at least 95% identical to SEQ ID NO;
56 and is capable of binding an OX-40L receptor, and(c) a linker linking the first domain and the second domain and comprising a hinge-CH2-CH3 Fc domain.
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Abstract
The present invention relates to, inter alia, compositions and methods, including chimeric proteins that find use in the treatment of disease, such as immunotherapies for cancer and autoimmunity. In part, the invention provides, in various embodiments, fusions of extracellular domains of transmembrane proteins that can have stimulatory or inhibitory effects.
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Citations
25 Claims
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1. A heterologous chimeric protein comprising:
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(a) a first domain comprising a portion of PD-1 that is at least 95% identical to SEQ ID NO;
32 and is capable of binding a PD-1 ligand,(b) a second domain comprising a portion of OX-40 ligand (OX40L) that is at least 95% identical to SEQ ID NO;
56 and is capable of binding an OX-40L receptor, and(c) a linker linking the first domain and the second domain and comprising a hinge-CH2-CH3 Fc domain. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
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22. A method for treating cancer comprising administering an effective amount of a pharmaceutical composition to a subject in need thereof, the pharmaceutical composition comprising:
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(a) a first domain comprising a portion of PD-1 that is at least 95% identical to SEQ ID NO;
32 and is capable of binding a PD-1 ligand,(b) a second domain comprising a portion of OX-40 ligand (OX40L) that is at least 95% identical to SEQ ID NO;
56 and is capable of binding an OX-40L receptor, and(c) a linker linking the first domain and the second domain. - View Dependent Claims (23)
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24. A recombinant fusion protein comprising:
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(a) a first domain comprising a portion of PD-1 that is at least 95% identical to the amino acid sequence of SEQ ID NO;
32 and is capable of binding a PD-1 ligand,(b) a second domain comprising a portion of OX-40 ligand (OX40L) that is at least 95% identical to the amino acid sequence of SEQ ID NO;
56 and is capable of binding an OX-40L receptor, and(c) a linker comprising an amino acid sequence that is at least 95% identical to SEQ ID NO;
72 and links the first domain and the second domain.
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25. A heterologous chimeric protein comprising:
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(a) a first domain comprising the amino acid sequence of SEQ ID NO;
32,(b) a second domain comprising the amino acid sequence of SEQ ID NO;
56, and(c) a linker linking the first domain and the second domain and comprising the amino acid sequence of SEQ ID NO;
72.
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Specification