Office Action 1: Notice of Allowance (2025-02-19)

CLAIMS:
AMENDMENTS TO THE CLAIMS:

This listing of claims will replace all prior versions and listings of claims in the application. Please amend the claims as follows.

Application No.: 18/658,421

1\. -74. (Canceled)273

75\. (New) An isolated nucleic acid that encodes a polypeptide comprising at least one VHH domain that binds OX40, wherein the VHH domain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10, a CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12, and wherein the VHH domain comprises a FR2 comprising the amino acid sequence of SEQ ID NO: 22.

76\. (New) The isolated nucleic acid of claim 75, wherein the VHH domain comprises a FR3 comprising the amino acid sequence of SEQ ID NO: 23.

77\. (New) The isolated nucleic acid of claim 75, wherein the VHH domain comprises the amino acid sequence of SEQ ID NO: 9.

78\. (New) The isolated nucleic acid of claim 75, wherein the polypeptide comprises two, three, or four VHH domains.

79\. (New) The isolated nucleic acid of claim 78, wherein each VHH domain binds OX40.

80\. (New) The isolated nucleic acid of claim 79, wherein each VHH domain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10, a CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12, and wherein each VHH domain comprises a FR2 comprising the amino acid sequence of SEQ ID NO: 22.

81\. (New) The isolated nucleic acid of claim 80, wherein each VHH domain comprises a FR3 comprising the amino acid sequence of SEQ ID NO: 23.

82\. (New) The isolated nucleic acid of claim 79, wherein each VHH domain comprises the amino acid sequence of SEQ ID NO: 9.

83\. (New) The isolated nucleic acid of claim 75, wherein the polypeptide comprises an Fc domain.

84\. (New) The isolated nucleic acid of claim 83, wherein the polypeptide comprising an Fc domain comprises an amino acid sequence selected from SEQ ID NOs: 25 and 26.
Application No.: 18/658,421

85\. (New) The isolated nucleic acid of claim 78, wherein the polypeptide comprises an Fc domain.

86\. (New) The isolated nucleic acid of claim 85, wherein the Fc domain comprises an amino acid sequence selected from SEQ ID NOs: 25 and 26.

87\. (New) The isolated nucleic acid of claim 75, wherein polypeptide comprises the amino acid sequence of SEQ ID NO: 14.

88\. (New) The isolated nucleic acid of claim 87, wherein the polypeptide comprises an Fc domain.

89\. (New) The isolated nucleic acid of claim 75, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 15.

90\. (New) An isolated nucleic acid that encodes a polypeptide that binds OX40 consisting of the amino acid sequence of SEQ ID NO: 15.

91\. (New) A vector comprising the isolated nucleic acid of claim 75.

92\. (New) A vector comprising the isolated nucleic acid of claim 87.

93\. (New) A vector comprising the isolated nucleic acid of claim 88.

94\. (New) A vector comprising the isolated nucleic acid of claim 89.

95\. (New) A host cell comprising the isolated nucleic acid of claim 75.

96\. (New) A host cell comprising the isolated nucleic acid of claim 87.

97\. (New) A host cell comprising the isolated nucleic acid of claim 88.

98\. (New) A host cell comprising the isolated nucleic acid of claim 89.

99\. (New) A host cell comprising the vector of claim 91.

100\. (New) A host cell comprising the vector of claim 92.

101\. (New) A host cell comprising the vector of claim 93.

102\. (New) A host cell comprising the vector of claim 94.

103\. (New) A host cell that expresses a polypeptide comprising at least one VHH domain that binds OX40, wherein the VHH domain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10, a CDR2 comprising the amino acid sequence of SEQ ID NO:
11, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12, and wherein each VHH domain comprises a FR2 comprising the amino acid sequence of SEQ ID NO: 22.

104\. (New) The host cell of claim 103, wherein the VHH domain comprises a FR3 comprising the amino acid sequence of SEQ ID NO: 23.

105\. (New) The host cell of claim 103, wherein the VHH domain comprises the amino acid sequence of SEQ ID NO: 9.

106\. (New) The host cell of claim 103, wherein the polypeptide comprises two, three, or four VHH domains.

107\. (New) The host cell of claim 106, wherein each VHH domain binds OX40.

108\. (New) The host cell of claim 107, wherein each VHH domain comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10, a CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a CDR3 comprising the amino acid sequence of SEQ ID NO:
12, and wherein each VHH domain comprises a FR2 comprising the amino acid sequence of SEQ ID NO: 22.

109\. (New) The host cell of claim 108, wherein each VHH domain comprises a FR3 comprising the amino acid sequence of SEQ ID NO: 23.

110\. (New) The host cell of claim 107, wherein each VHH domain comprises the amino acid sequence of SEQ ID NO: 9.

111\. (New) The host cell of claim 103, wherein the polypeptide comprises an Fc domain.

112\. (New) The host cell of claim 111, wherein the polypeptide comprising an Fc domain comprises an amino acid sequence selected from SEQ ID NOs: 25 and 26.

113\. (New) The host cell of claim 106, wherein the polypeptide comprises an Fc domain.

114\. (New) The host cell of claim 113, wherein the Fc domain comprises an amino acid sequence selected from SEQ ID NOs: 25 and 26.

115\. (New) The host cell of claim 103, wherein polypeptide comprises the amino acid sequence of SEQ ID NO: 14.

116\. (New) The host cell of claim 115, wherein the polypeptide comprises an Fc domain.

117\. (New) The host cell of claim 103, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 15.
Application No.: 18/658,421

118\. (New) The host cell of claim 103, which secretes the polypeptide.

119\. (New) The host cell of claim 103, which is a primary human cell.

120\. (New) The host cell of claim 119, which is a primary human T cell.

121\. (New) The host cell of claim 120, which is a chimeric antigen receptor (CAR)-T cell.

OFFICE ACTION:
Notice of Pre-AIA  or AIA  Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's preliminary amendment, dated August 29, 2024, has been entered. By way of this submission, Applicant has cancelled claims 1-74 and introduced new claims 75-121.
Claims 75-121 are allowed.
The following is an examiner’s statement of reasons for allowance: The claimed sequences have been searched and found to be free of the art. The closest prior art is Blein (WO2018115003A2, cited in IDS). Blein teaches a humanized antibody Tetra-hz 1D10 which binds OX40 (page 59). Blein further teaches that OX40-binding agonist antibodies are useful in T cell differentiation and cytolytic function leading to enhanced anti-tumor immunity against a variety of tumors in a subset of patients (page 1, last paragraph). However, Blein does not teach the claimed CDR sequences in combination with the claimed FR2 sequence.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee.  Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”



CITED REFERENCE SUMMARIES: Ref WO2018115003A2: Claims:
Claims 1. A TNFR agonist comprising binding portions specific to at least two different parts of said TNFR. 2. The TNFR agonist of claim 1, wherein said TNFR is involved in the costimulation of T cell responses. 3. The TNFR agonist of claim 1 or 2, wherein said TNFR is selected from the group comprising: CD27, 4-1BB (CD137), OX40 (CD134), HVEM, CD30, and GITR. 4. The TNFR agonist of any one of claims 1 to 3, wherein said binding portions can bind to said TNFR simultaneously. 5. The TNFR agonist according to anyone of claims 1 to 4, comprising at least two binding portions to each part of said TNFR bound by said agonist. 6. The TNFR agonist of anyone of claims 1 to 5, wherein said binding portions are selected from the group comprising antibodies, DARPins, Fynomers, Affimers, variable lymphocyte receptors, anticalin, nanofitin, variable new antigen receptor (VNAR), and derivatives thereof such as such as a Fab, Fab', Fab'-SH, Fd, Fv, dAb, F(ab')2, scFv, Fcabs, bispecific single chain Fv dimers, diabodies, triabodies. 7. The TNFR agonist of claim 5 or 6, wherein said at least two binding portions which bind to the same part of said TNFR are disposed at the same peptide terminus of said agonist. 8. The TNFR agonist of anyone of claims 1 to 7, wherein said binding portions bind to different cysteine-rich domains (CRD) of said TNFR. 9. The TNFR agonist of anyone of claims 1 to 8, which agonises OX40 and binds to epitopes in CRD 1 and CRD 3 or CRD 1 and CRD 4 of OX40. 10. The TNFR agonist of claim 9 wherein at least one OX40 binding portion is selected from the group comprising: SEQ. ID NO: 2, 3, 12, 13, 14, 15, 16, 17, 18, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or isolated polypeptides having an amino acid sequence that is at least 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto. 11. An OX40 agonist is encoded by SEQ. ID Nos: 45 and 16 or isolated polypeptides having an amino acid sequence that is at least 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% thereto. 12. Use of an agonist according to anyone of claims 1 to 11 as a medicament. 13. Use of an agonist according to anyone of claims 1 to 11 to activate components of the human immune system. 14. Use of an OX40 agonist according to any one of claims 1 to 11 as a medicament. 15. The use according to any one of claims 12 to 14, in combination with another medicament.
A TNFR agonist comprising binding portions specific to at least two different parts of said TNFR.
The TNFR agonist of claim 1, wherein said TNFR is involved in the costimulation of T cell responses.
The TNFR agonist of claim 1 or 2, wherein said TNFR is selected from the group comprising: CD27, 4-1BB (CD137), OX40 (CD134), HVEM, CD30, and GITR.
The TNFR agonist of any one of claims 1 to 3, wherein said binding portions can bind to said TNFR simultaneously.
The TNFR agonist according to anyone of claims 1 to 4, comprising at least two binding portions to each part of said TNFR bound by said agonist.
The TNFR agonist of anyone of claims 1 to 5, wherein said binding portions are selected from the group comprising antibodies, DARPins, Fynomers, Affimers, variable lymphocyte receptors, anticalin, nanofitin, variable new antigen receptor (VNAR), and derivatives thereof such as such as a Fab, Fab', Fab'-SH, Fd, Fv, dAb, F(ab')2, scFv, Fcabs, bispecific single chain Fv dimers, diabodies, triabodies.
The TNFR agonist of claim 5 or 6, wherein said at least two binding portions which bind to the same part of said TNFR are disposed at the same peptide terminus of said agonist.
The TNFR agonist of anyone of claims 1 to 7, wherein said binding portions bind to different cysteine-rich domains (CRD) of said TNFR.
The TNFR agonist of anyone of claims 1 to 8, which agonises OX40 and binds to epitopes in CRD 1 and CRD 3 or CRD 1 and CRD 4 of OX40.
The TNFR agonist of claim 9 wherein at least one OX40 binding portion is selected from the group comprising: SEQ. ID NO: 2, 3, 12, 13, 14, 15, 16, 17, 18, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or isolated polypeptides having an amino acid sequence that is at least 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto.
An OX40 agonist is encoded by SEQ. ID Nos: 45 and 16 or isolated polypeptides having an amino acid sequence that is at least 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% thereto.
Use of an agonist according to anyone of claims 1 to 11 as a medicament.
Use of an agonist according to anyone of claims 1 to 11 to activate components of the human immune system.
Use of an OX40 agonist according to any one of claims 1 to 11 as a medicament.
The use according to any one of claims 12 to 14, in combination with another medicament.