Non-human primate Fc receptors and methods of use
AssigneeGenentech, Inc.
InventorsLeonard G. Presta, Angela K. Namenuk
Life of this patent
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Abstract
The invention provides isolated non-human primate Fc receptor polypeptides, the nucleic acid molecules encoding the Fc receptor polypeptides, and the processes for production of recombinant forms of the Fc receptor polypeptides, including fusions, variants, and derivatives thereof. The invention also provides methods for evaluating the safety, efficacy and biological properties of Fc region containing molecules using the non-human primate Fc receptor polypeptides.
Claims90
An isolated nucleic acid comprising a polynucleotide sequence that encodes a non-human primate Fc receptor polypeptide with an amino acid sequence of SEQ ID NO:
- 9, SEQ ID NO:
- 11, SEQ ID NO:
- 15, SEQ ID NO:
- 17, SEQ ID NO:
- 18, SEQ ID NO:
- 20, SEQ ID NO:
- 25, SEQ ID NO:
- 29, SEQ ID NO:
- 64 or fragments thereof.
A method for obtaining a nucleic acid sequence encoding an Fc receptor polypeptide comprising:
- a) amplifying a nucleic acid from a nonhuman primate cell with a primer set comprising a forward and a reverse primer, wherein the primer sets are selected from the group consisting of SEQ ID NO:31 and SEQ ID NO:32, SEQ ID NO:33 and SEQ ID NO:34, SEQ ID NO:35 and SEQ ID NO:36, SEQ ID NO:37 and SEQ ID NO:38, SEQ ID NO:39 and SEQ ID NO:40, SEQ ID NO:41 and SEQ ID NO:42, SEQ ID NO:43 and SEQ ID NO:44, SEQ ID NO:45 and SEQ ID NO:46, SEQ ID NO:47 and SEQ ID NO:48, SEQ ID NO:49 and SEQ ID NO:50, SEQ ID NO:51 and SEQ ID NO:52, and SEQ ID NO:53 and SEQ ID NO:54;
- b) isolating the amplified nucleic acid.
An isolated polypeptide comprising an amino acid sequence of SEQ ID NO:
- 9 or SEQ ID NO:
- 65, or fragment thereof.
An isolated polypeptide comprising an amino acid sequence of SEQ ID NO:
- 15 or SEQ ID NO:
- 66, or fragment thereof.
An isolated polypeptide comprising an amino acid of SEQ ID NO:
- 17 or SEQ ID NO:
- 67, or fragment thereof.
An isolated polypeptide comprising an amino acid sequence of SEQ ID NO:
- 18 or SEQ ID NO:
- 68, or fragment thereof.
An isolated polypeptide comprising an amino acid sequence of SEQ ID NO:
- 20 or SEQ ID NO:
- 69, or fragment thereof.
An isolated polypeptide comprising an amino acid sequence of SEQ ID NO:
- 29 or SEQ ID NO:
- 64, or SEQ ID NO:
- 71, or SEQ ID NO:
- 72, or fragment thereof.
An isolated polypeptide comprising an amino acid sequence of SEQ ID NO:
- 25 or SEQ ID NO:
- 70.
An isolated polypeptide comprising an amino acid sequence of SEQ ID NO:
- 11.
An isolated fusion protein comprising a heterologous polypeptide joined to a Fc receptor polypeptide fragment having an aminoacid sequence of Δ1 to Δ269 of SEQ ID NO:65.
An isolated fusion protein comprising a heterologous polypeptide joined to a Fc receptor polypeptide fragment having an aminoacid sequence of Δ1 to Δ182 of SEQ ID NO:66.
An isolated fusion protein comprising a heterologous polypeptide joined to a Fc receptor polypeptide fragment having an aminoacid sequence of Δ2 to Δ184 of SEQ ID NO:68.
An isolated fusion protein comprising a heterologous polypeptide joined to a Fc receptor polypeptide fragment having an aminoacid sequence of Δ1 to Δ187 of SEQ ID NO:69.
An isolated fusion protein comprising a heterologous polypeptide joined to a Fc receptor polypeptide fragment having an aminoacid sequence of Δ1 to Δ274 of SEQ ID NO:71 or SEQ ID NO:72.
An isolated polypeptide variant having an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO:
- 9.
An isolated polypeptide variant having an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO:
- 15.
An isolated polypeptide variant having an amino acid sequence having at least 98% sequence identity with the amino acid sequence of SEQ ID NO:
- 17.
An isolated polypeptide variant having an amino acid sequence having at least 92% sequence identity with the amino acid sequence of SEQ ID NO:
- 18.
An isolated polypeptide variant having an amino acid sequence having at least 92% sequence identity with the amino acid sequence of SEQ ID NO:
- 20.
An isolated polypeptide variant having an amino acid sequence having at least 93% sequence identity with the amino acid sequence of SEQ ID NO:
- 25.
An isolated polypeptide variant having an amino acid sequence having at least 97% sequence identity with the amino acid sequence of SEQ ID NO:
- 29.
A method for evaluating at least one biological property of an Fc region containing molecule comprising:
- a) contacting an isolated non-human primate Fc receptor polypeptide with an Fc region containing molecule;
- and
- b) determining the effect of the contact on at least one biological property of the Fc region containing molecule.
A method for identifying an agent that has an increased affinity for at least one cynomolgus Fc receptor polypeptide with an ITAM region compared to human Fc receptor polypeptide comprising:
- a) determining the binding affinity of the agent to at least one cynomolgus Fc receptor polypeptide associated a polypeptide with an ITAM region;
- b) determining the binding affinity of the agent to the corresponding human Fc receptor polypeptide;
- and
- c) selecting agents that have an increased affinity for the cynomolgus Fcy receptor polypeptide associated with a polypeptide with an ITAM region compared to the corresponding human Fc receptor.
A method for identifying an agent that has an altered affinity for a cynomolgus Fc receptor polypeptide with an ITIM region compared to corresponding human Fc receptor polypeptide comprising:
- a) determining a binding affinity for the agent to be at least one cynomolgus FcγRIIB receptor polypeptide;
- b) determining a binding affinity of the agent to corresponding human FcγRIIB receptor polypeptide;
- and
- c) selecting agents with altered affinity for a cynomolgus FcγRIIB receptor polypeptide with an ITIM region compared to corresponding human FcγRIIB polypeptide.
A method for identifying an agent with increased binding affinity for a cynomolgus Fc receptor polypeptide with an ITAM region and decreased affinity for a cynomolgus Fc receptor polypeptide with an ITIM region comprising:
- a) determining a binding affinity of the agent for at least one cynomolgus Fc receptor polypeptide associated with an ITAM region and a binding affinity of the agent to the corresponding human Fc receptor polypeptide;
- b) determining the binding affinity of the agent for at least one cynomolgus Fc receptor polypeptide with an ITIM region and a binding affinity of the agent for the corresponding human Fc receptor polypeptide;
- and
- c) selecting an agent with enhanced binding for a cynomolgus Fc receptor polypeptide with an ITAM region and a decreased affinity for a cynomolgus Fc receptor polypeptide with an ITIM region compared to the corresponding human Fc receptor polypeptides.
An isolated nucleic acid comprising a polynucleotide sequence that encodes a non-human primate Fc receptor polypeptide with an amino acid sequence of SEQ ID NO:
- 65, SEQ ID NO:
- 66, SEQ ID NO:
- 67, SEQ ID NO:
- 68, SEQ ID NO:
- 69, SEQ ID NO:
- 70, SEQ ID NO:
- 71, SEQ ID NO:
- 72 or fragments thereof.
Dependencies are inferred from the claim text.