DETAILED 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 .
Claims Status
Claims 1-24 and 33 are pending.
Claims 1, 3, 5-8, and 16 are amended.
Claims 9-13, and 33 are canceled.
Election/Restrictions
Applicant’s election without traverse of claims 1-24 and 33 in the reply filed on September 19, 2025 is acknowledged.
Claims 25-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 19, 2025.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/23/2026, 05/01/2025, 11/30/2023, and 09/16/2022 is acknowledged. The submission is in compliance with the provision of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered.
Claim Objections
Claim 22 is objected to because of the following informalities:
Claim 22 is dependent on rejected claim 1. Appropriate correction is required.
Claim 23 objected to because of the following informalities:
Claim 23 is dependent on rejected claim 1. Appropriate correction is required.
Claim 24 objected to because of the following informalities:
Claim 24 is dependent on rejected claim 23. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
(previous rejection, withdrawn) Claim 33 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Response to Arguments
Applicant’s arguments, see pg. 9, filed 04/02/2026, with respect to claim 33 have been fully considered and are persuasive. Applicant has canceled claim 33 rending the rejection moot. The rejection of 01/02/2026 has been withdrawn.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
(previous rejection, withdrawn) Claims 1-3, 9, and 11-12 are rejected under 35 U.S.C. 102 (a1) as being anticipated by Kong et al. (Biochem. Cell. Biol., Vol. 85, pg. 685-695) hereinafter referred to as Kong et al..
Response to Arguments
Applicant’s arguments, see pg. 8 and 9, filed 04/02/2026, with respect to the rejection(s) of claim(s) 1-3, 9, 11, and 12 under 35 U.S.C. 102(a)(1) have been fully considered and are persuasive. Applicant has amended base claim 1, to incorporate, in part, previous claims 13 and 33. Applicant has canceled claims 9 and 11-12 rendering the rejection of claims 9 and 11-12 moot. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Applicant’s amendment of claim 1.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
(new rejection, necessitated by amendment) Claims 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over unpatentable over Kong et al. (Biochem. Cell. Biol. Vol. 85, pg. 685-695, 2007), hereinafter referred to as Kong et al., in view of Ast et al. (US Patent No: US 9,266,938 B2; Feb. 23, 2016), hereinafter referred to as Ast et al. and further in view of Swanson et al. (US Patent Application Publication US 2019/0135922 A1; May 9, 2019), hereinafter referred to as Swanson et al.
Kong et al. teach a fusion protein comprising an IL-2 cytokine fused to the extracellular region of B7.1 (IgV+C) (CD80) via a flexible spacer designed so that the protein correctly folds into its three-dimensional structure (Paragraph 5 and pg. 686 and Figure 1, pg. 688). The fusion protein is proposed to function as a more effective bifunctional fusion protein for immunotherapeutic treatment for tumors resulting in a stronger stimulation of T-cell proliferation than either the B7.1(IgV+C) or IL-2 alone (see abstract, pg. 685). Kong et al. teach that two important genes encoding two costimulatory molecules, IL-2 and B7.1 (IgV+C) (CD80) were ligated and cloned into an expression vector and subsequently expressed and purified (Paragraph 5, pg. 694). Furthermore, Kong et al. teach that the IL-2-B7.1(IgV+C) fusion protein strongly promotes the activation and proliferation of T lymphocytes (last paragraph, pg. 694) and that the linkage between IL-2 and B7.1 ensures that IL-2 and B7.1 exert a synergistic effect on T lymphocyte activation (last paragraph, pg. 694).
Kong et al. does not teach certain mutations within the IL-2 portion of the bifunctional fusion protein or that the CD80 protein fragment “comprises the amino acid sequence of amino acid residues of amino acid residues … of SEQ ID NO: 11” or the variant of the CD80 protein fragment comprises amino acid sequence of the CD80 protein fragment having a combination of amino acid substitutions relative to SEQ ID NO: 2.
Ast et al. teach an enhancement of the therapeutic usefulness of IL-2 proteins by providing mutant IL-2 polypeptides to overcome problems with IL-2 immunotherapy (Column 3, lines 47-66). Furthermore, Ast et al. teach that the mutant IL-2 polypeptides can be used as immunotherapeutic agents, for example, in the treatment of cancer (Column 57, lines 6-10). With regards to issues with IL-2 immunotherapy, Ast et al. teach that the interaction of IL-2 with the a-subunit (CD25) of the trimeric, high affinity IL-2 receptor is responsible for the problems associated with IL-2 immunotherapy (Column 3, lines 57-60). Ast et al. teach that association of the IL-2R a, b, and g subunits result in a trimeric, high-affinity IL-2 receptor. The dimeric IL-2 receptor consists of only the b and g subunit and is termed an intermediate-affinity IL-2 receptor. While possessing lower affinity for IL-2, the intermediate-affinity IL-2 receptor still maintains the b and g subunits that are crucial for signal transduction (column 1, lines 50-56). Accordingly, Ast et al. teach exemplary mutations that abolish or reduce affinity of the mutant IL-2 polypeptide to the high-affinity IL-2 receptor while preserving affinity for the intermediate-affinity IL-2 receptor (Column 3, lines 61-67). Ast et al. teach one or more exemplary amino acid substitutions to SEQ ID NO:1 (Column 4, lines 1-2; which is equivalent to SEQ ID NO: 10 of claim 3 of current instant application) at positions 38, 42, 45, or 72 or a combination of exemplary mutations such as R38A, F42A, Y45A and L72G that have decreased affinity to CD25 but retain substantial similar binding to the intermediate IL-2 receptor (Column 17, lines 10-26). CD25 refers to the a-subunit of IL-2 (Column 1, lines 49-50).
Thus, it would have been obvious to someone of the ordinary skill in the art before the effective filing date of the claimed invention to be motivated by the teachings of Ast et al. to incorporate the IL-2 R38A mutation taught by Ast et al. (equivalent to SEQ ID NO. 6 in claim 8 of current instant application) and a combination of amino acid substitutions at positions 38 (R38A), 42 (F42A) or 72 (L72G) (such as R38A/F42A/L72G, corresponding to SEQ ID NO: 24 in claim 8 of current instant application) into the IL-2 domain of the bifunctional fusion protein taught by Kong et al. in order to reduce binding affinity of IL-2 to the a-subunit of the high-affinity trimeric IL-2 receptor and preserve binding to the intermediate IL-2 receptor. The expectation of success would be high based upon the high level of skill in the art in the area of recombinant protein engineering as exemplified by Kong et al. and Ast et al. who teach all the methods and component is necessary to produce the obvious mutant fusion.
Swanson et al. teach a fusion protein comprising a variant CD80 polypeptide that is linked to an Fc domain via a linker (see pg. 110, claims 85-90) for targeting tumors (pg. 113, claims 177-178). The variant CD80 polypeptides can antagonize or stimulate the biological activity of its cognate binding partner such as CD28, PD-L1, and/or CLTA-4 and can be used to promote immunity in oncology or treatment of inflammation or autoimmunity (Paragraph 0198, pg. 37). Swanson et al. teach exemplary mutations K89E/T130A to SEQ ID NO: 28 (CD80 residues 35-242 which is equivalent to SEQ ID NO: 11 of the current instant application and comprises amino acid residues of SEQ ID NO: 2 of the current instant application) (see sequence alignment below) (Paragraph 0179, pg. 26)
RESULT 1
US-17-912-403A-2
Query Match 71.7%; Score 1102; DB 1; Length 208;
Best Local Similarity 100.0%;
Matches 208; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 35 VIHVTKEVKEVATLSCGHNVSVEELAQTRIYWQKEKKMVLTMMSGDMNIWPEYKNRTIFD 94
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 VIHVTKEVKEVATLSCGHNVSVEELAQTRIYWQKEKKMVLTMMSGDMNIWPEYKNRTIFD 60
Qy 95 ITNNLSIVILALRPSDEGTYECVVLKYEKDAFKREHLAEVTLSVKADFPTPSISDFEIPT 154
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ITNNLSIVILALRPSDEGTYECVVLKYEKDAFKREHLAEVTLSVKADFPTPSISDFEIPT 120
Qy 155 SNIRRIICSTSGGFPEPHLSWLENGEELNAINTTVSQDPETELYAVSSKLDFNMTTNHSF 214
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SNIRRIICSTSGGFPEPHLSWLENGEELNAINTTVSQDPETELYAVSSKLDFNMTTNHSF 180
Qy 215 MCLIKYGHLRVNQTFNWNTTKQEHFPDN 242
||||||||||||||||||||||||||||
Db 181 MCLIKYGHLRVNQTFNWNTTKQEHFPDN 208
that can exhibit increased binding affinity to one or more of CD28, PD-L1, or CTLA-4 molecules compared to a wild-type or unmodified CD80 polypeptide (Paragraph 0180, pg. 28). With regards to therapeutic utility, Swanson et al. teach that the variant CD80 polypeptides are used to treat inflammatory or autoimmune disorders, cancer and other ailments (Paragraph 402, pg. 65).
Thus, it would have been obvious to someone of the ordinary skill in the art before the effective filing date of the claimed invention to be motivated by the teachings of Ast et al. to incorporate the IL-2 R38A mutation taught by Ast et al. (equivalent to SEQ ID NO. 6 in claim 8 of current instant application) and a combination of amino acid substitutions at positions 38 (R38A), 42 (F42A) or 72 (L72G) (such as R38A/F42A/L72G, corresponding to SEQ ID NO: 24 in claim 8 of current instant application) into the IL-2 domain of the bifunctional fusion protein taught by Kong et al. in order to reduce binding affinity of IL-2 to the a-subunit of the high-affinity trimeric IL-2 receptor and preserve binding to the intermediate IL-2 receptor.
It would have been further obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to modify the B7.1 (IgV+C) (CD80) domain in the context of the fusion protein taught by Kong et al. with the CD80 fragment (35-242) harboring the exemplary K89E/T130A mutation taught by Swanson et al in order to increase binding affinity to cognate binding partners.
The expectation of success would be high based upon the high level of skill in the art in the area of recombinant protein engineering as exemplified by Kong et al., Ast et al. and Swanson et al. who teach all the methods and components that are necessary to produce the obvious mutant fusion protein.
(new rejection, necessitated by amendment) Thus, claims 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over unpatentable over Kong et al. (Biochem. Cell. Biol. Vol. 85, pg. 685-695, 2007), hereinafter referred to as Kong et al., in view of Ast et al. (US Patent No: US 9,266,938 B2; Feb. 23, 2016), hereinafter referred to as Ast et al. and further in view of Swanson et al. (US Patent Application Publication US 2019/0135922 A1; May 9, 2019), hereinafter referred to as Swanson et al.
(previous rejection, withdrawn) Claims 4-8 are rejected under 35 U.S.C. 103 as being unpatentable over Kong et al. (Biochem. Cell. Biol. Vol. 85, pg. 685-695, 2007), hereinafter referred to as Kong et al., in view of Ast et al. (US Patent No: US 9,266,938 B2; Feb. 23, 2016), hereinafter referred to as Ast et al..
Response to Arguments
Applicant’s arguments, see pg. 8 and 10, filed 04/02/2026, with respect to the rejection(s) of claim(s) 4-8 under 35 U.S.C. 103 have been fully considered and are persuasive. Applicant argues that Kong et al. fails to disclose or teach a fusion protein consisting of CD80 protein fragment or a variant thereof and an IL-2 variant. The Examiner does not find this argument persuasive as Kong et al. teaches a recombinant fusion protein of IL-2 fused to the extracellular region of CD80 via a flexible linker (see Paragraph 5 and pg. 686 and Figure 1, pg. 688). Additionally, Applicant argues the following: Ast et al., while it discloses dozens of examples of antigen-binding moieties, fails to disclose or teach CD80 protein fragment or variant thereof, or even a wild type -CD80 protein; Swanson et al. neither discloses nor teaches the CD80 fragments or the CD80 variant of the claimed fusion protein and also fails to disclose or teach an IL-2 protein or variant. Applicant’s argue that it would not have been obvious to one of ordinary skill in the art to derive the claimed fusion protein from the combination of Kong et al, Ast et al., Swanson et al, and Qin et al. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). Additionally, according the MPEP 2145 (IV), “One cannot show nonobviousness by attacking references individually where the rejections are based on a combination of references”. In this case, the combined teachings of Kong et al, Ast et al., and Swanson et al. provide all the teachings and guidance to motivate one of ordinary skill in the art to arrive at the fusion protein described in claims 1 and dependent claims 4-8 as summarized in the rejections above.
However, Applicants have amended claim 1 (which claims 4-8 are dependent on) to incorporate, in part, previous claims 13 and 33. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Applicant’s amendment of claim 1 and claims 5-7.
(previous rejection, withdrawn) Claims 10 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Kong et al. (Biochem. Cell. Biol. Vol. 85, pg. 685-688, 2007) in view of Swanson et al. (US Patent Application Publication US 2019/0135922 A1; May 9, 2019), hereinafter referred to as Swanson et al.
Response to Arguments
Applicant’s arguments, see pg. 8 and 10, filed 04/02/2026, with respect to the rejection(s) of claim(s) 10 and 13 under 35 U.S.C. 103 have been fully considered and are persuasive. Applicant has canceled claim 10 and 13 rendering the rejection moot. Therefore, the rejection of 01/02/2026 has been withdrawn.
(previous rejection, withdrawn) Claims 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Kong et al. (Biochem. Cell. Biol. Vol. 85, pg. 685-695) in view of Swanson et al. (US Patent Application Publication US 2019/0135922 A1; May 9, 2019) and further in view of Ast et al. (US Patent No: US 9,266,938 B2; Feb. 23, 2016).
Response to Arguments
Applicant’s arguments, see pg. 10, filed 04/02/2026, with respect to the rejection(s) of claim(s) 14-17 under 35 U.S.C. 103 have been fully considered and are persuasive. Applicant argues that Kong et al. fails to disclose or teach a fusion protein consisting of CD80 protein fragment or a variant thereof and an IL-2 variant. The Examiner does not find this argument persuasive as Kong et al. teaches a recombinant fusion protein of IL-2 fused to the extracellular region of CD80 via a flexible linker (see Paragraph 5 and pg. 686 and Figure 1, pg. 688). Additionally, Applicant argues the following: Ast et al., while it discloses dozens of examples of antigen-binding moieties, fails to disclose or teach CD80 protein fragment or variant thereof, or even a wild type -CD80 protein; Swanson et al. neither discloses nor teaches the CD80 fragments or the CD80 variant of the claimed fusion protein and also fails to disclose or teach an IL-2 protein or variant; Qin et al. fail to disclose or teach both IL-2 protein and a variant therof,: and CD80 protein, a fragment thereof, or a variant thereof. Applicant’s argue that it would not have been obvious to one of ordinary skill in the art to derive the claimed fusion protein from the combination of Kong et al, Ast et al., Swanson et al, and Qin et al. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). Additionally, according the MPEP 2145 (IV), “One cannot show nonobviousness by attacking references individually where the rejections are based on a combination of references”. In this case, the combined teachings of Kong et al, Ast et al., Swanson et al, and Qin et al. provide all the teachings and guidance to motivate one of ordinary skill in the art to arrive at the fusion protein described in claims 1 and 4-8 as summarized in the rejections above.
However, Applicants argue that claim 1 has been amended to incorporate, in part, previous claims 13 and 33 (see pg. 8 and 10) which claims 14-17 are dependent on. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of amendment to claim 1.
(new rejection, necessitated by amendments) Claims 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Kong et al. (Biochem. Cell. Biol. Vol. 85, pg. 685-695) in view of Swanson et al. (US Patent Application Publication US 2019/0135922 A1; May 9, 2019) and further in view of Ast et al. (US Patent No: US 9,266,938 B2; Feb. 23, 2016).
The teachings of Kong et al., Swanson et al., and Ast et al. as applied to claim 1 is summarized above.
With regards to claim 14, Swanson et al. teach that conjugates such as an albumin molecule can be used to derivatize an immunomodulatory polypeptide having a variant CD80 polypeptide to increase the biological half-life of the polypeptide (Paragraph 0088, pg. 12). Ast et al. also teach that an IL-2 polypeptide can be fused to another moiety such as albumin resulting in an extended half-life of IL-2 in circulation (Column 21, lines 45-60).
It would therefore have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to be motivated to modify the bifunctional IL-2-B7.1 fusion protein of claim 1 as described by the combined teachings of Kong et al., Swanson et al., and Ast et al. summarize above by incorporating an albumin linker between the CD80 and IL-2 polypeptides in order to increase the biological half-life of the fusion protein. Claims 15-17 are included in this rejection based upon their dependence on claim 14 in the alternative. The expectation of success would be high based upon the high level of skill in the art in the area of recombinant protein engineering as exemplified by Kong et al., Swanson et al., and Ast et al. who teach all the methods and component is necessary to produce the modified fusion protein linked to albumin.
(new rejection, necessitated by amendment) Claims 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Kong et al. (Biochem. Cell. Biol. Vol. 85, pg. 685-695) in view of Swanson et al. (US Patent Application Publication US 2019/0135922 A1; May 9, 2019) and further in view of Ast et al. (US Patent No: US 9,266,938 B2; Feb. 23, 2016).
(previous rejection, withdrawn) Claims 18, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Kong et al. (Biochem. Cell. Biol. Vol. 85, pg. 685-695) in view of Swanson et al. (US Patent Application Publication US 2019/0135922 A1; May 9, 2019) and in further view of Ast et al. (US Patent No: US 9,266,938 B2; Feb. 23, 2016).
Response to Arguments
Applicant’s arguments, see pg. 8 and 10, filed 04/02/2026, with respect to the rejection(s) of claim(s) 18 and 20-21 under U.S.C. 103 have been fully considered and are persuasive.
Applicant argues that Kong et al. fails to disclose or teach a fusion protein consisting of CD80 protein fragment or a variant thereof and an IL-2 variant. The Examiner does not find this argument persuasive as Kong et al. teaches a recombinant fusion protein of IL-2 fused to the extracellular region of CD80 via a flexible linker (see Paragraph 5 and pg. 686 and Figure 1, pg. 688). Additionally, Applicant argues the following: Ast et al., while it discloses dozens of examples of antigen-binding moieties, fails to disclose or teach CD80 protein fragment or variant thereof, or even a wild type -CD80 protein; Swanson et al. neither discloses nor teaches the CD80 fragments or the CD80 variant of the claimed fusion protein and also fails to disclose or teach an IL-2 protein or variant. Applicant’s argue that it would not have been obvious to one of ordinary skill in the art to derive the claimed fusion protein from the combination of Kong et al, Ast et al., Swanson et al, and Qin et al. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). Additionally, according the MPEP 2145 (IV), “One cannot show nonobviousness by attacking references individually where the rejections are based on a combination of references”. In this case, the combined teachings of Kong et al, Ast et al., and Swanson et al. provide all the teachings and guidance to motivate one of ordinary skill in the art to arrive at the fusion protein described in claims 1 and dependent claims 18 and 20-21 as summarized in the rejections above.
However, Applicant has incorporated , in part, previous claims 13 and 33 into amended claim 1 (see pg. 9 and 10) to which claims 18 and 20-21 are dependent on. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of amendment of claim 1.
(new rejection, necessitated by amendment) Claims 18, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Kong et al. (Biochem. Cell. Biol. Vol. 85, pg. 685-695) in view of Swanson et al. (US Patent Application Publication US 2019/0135922 A1; May 9, 2019) and in further view of Ast et al. (US Patent No: US 9,266,938 B2; Feb. 23, 2016).
The teachings of Kong et al., Swanson et al., and Ast et al. as applied to claim 1 are summarized above.
Swanson et al. teach a fusion protein having a variant CD80 polypeptide that is linked to an Fc domain via a linker (see pg. 110, claims 85-90) for targeting tumors (pg. 113, claims 177-178). Although Swanson et al. do not teach a fusion between CD80 and IL-2, Swanson et al., do teach that the variant CD80 polypeptide is linked to a moiety such as an Fc domain or variant thereof (via a linker) that increases the biological half-life of the polypeptide (Paragraph 0032, pg. 7). Furthermore, Swanson et al. teach that the linker between CD80 and the Fc domain can be one or more “peptide linkers” such as GGGGS (equivalent to SEQ ID NO. 5 in Claim 20 of the current instant application) or multimers of the GGGGS linker (Paragraph 0222, pg. 40). Furthermore, Swanson et al. teach that various peptide linkers are known in the art and can be optimally used to link an Fc to a fusion partner to generate a Fc-fusion heterodimer (Paragraph 0110, pg. 15). Additionally, Swanson et al. teach that the attachment of the CD80 polypeptide can be at the C- or N-terminus of the Fc and that two or more CD80 variant polypeptides can be independently attached at the N-terminus and C-terminus (Paragraph 0207, pg. 38).
Ast et al. teach IL-2 fusion proteins such as IL-2 immunoconjugates that have a mutant IL-2 polypeptide fused to a non-IL-2 moiety such as an Fc domain that can be a representative of the IgG class (Column 22, lines 17-24) such as IgG4 (Column 13, lines 1-3). Ast et. al teach that the benefits of the immunoconjugate such as IgG4 include that the antigen binding moiety of the immunoconjugate can recognize a tumor-specific epitope and result in targeting the immunoconjugate molecule to the tumor site (Column 21, lines 31-35). Ast et al. teach that IL-2 can be linked to the antigen moiety by various linkers such as peptides that include (G4S)n, (SG4), or G4(SG4)n linker peptides where n is generally a number between 1 and 10 (Column 27, lines 30-37).
It would therefore have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to be motivated to modify the IL-2-B7.1(IgV+C) fusion protein arrived at by the combined teachings of Kong et al., Swanson et al, and Ast et al. as applied to claim 1 by fusing the CD80-peptide linker-Fc molecule taught by Swanson et al. with the IL-2-peptide linker-Fc molecule taught by Ast et al. Since both Swanson et al. and Ast et al. both teach a fusion to an exemplary Fc such as IgG4 that improves biological half-life, one skilled in the art would be motivated to choose the IgG4 Fc as the linker in order to improve the biological half-life and install tumor-targeting properties to the bifunctional fusion protein. One skilled in the art, would also be knowledgeable in experimenting with designing both structural formula I and structural formula II in claim 18 of the current instant application as reasonable options. The expectation of success would be high based upon the high level of skill in the art in the area of recombinant protein engineering as exemplified by Kong et al., Swanson et al. and Ast et al. who teach all the methods and component is necessary to produce the obvious fusion protein with CD80 and IL-2 linked to Fc.
(new rejection necessitated by amendment) Thus claims 18, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Kong et al. (Biochem. Cell. Biol. Vol. 85, pg. 685-695) in view of Swanson et al. (US Patent Application Publication US 2019/0135922 A1; May 9, 2019) and in further view of Ast et al. (US Patent No: US 9,266,938 B2; Feb. 23, 2016).
(previous rejection, withdrawn) Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Kong et al. (Biochem. Cell. Biol. Vol. 85, pg. 685-695) in view of Swanson et al. (US Patent Application Publication US 2019/0135922 A1; May 9, 2019) and in further view of Ast et al. (US Patent No: US 9,266,938 B2; Feb. 23, 2016) as applied to claim 18 above, and further in view of Qin (US Patent No: 9,745,359B2; Aug. 29, 2017) hereinafter referred to as Qin.
Response to Arguments
Applicant’s arguments, see pg. 10, filed 04/02/2026, with respect to the rejection(s) of claim(s) 19 under 35 U.S.C. 103 have been fully considered and are persuasive. Applicant argues that Kong et al. fails to disclose or teach a fusion protein consisting of CD80 protein fragment or a variant thereof and an IL-2 variant. The Examiner does not find this argument persuasive as Kong et al. teaches a recombinant fusion protein of IL-2 fused to the extracellular region of CD80 via a flexible linker (see Paragraph 5 and pg. 686 and Figure 1, pg. 688). Additionally, Applicant argues the following: Ast et al., while it discloses dozens of examples of antigen-binding moieties, fails to disclose or teach CD80 protein fragment or variant thereof, or even a wild type -CD80 protein; Swanson et al. neither discloses nor teaches the CD80 fragments or the CD80 variant of the claimed fusion protein and also fails to disclose or teach an IL-2 protein or variant; Qin et al. fail to disclose or teach both IL-2 protein and a variant therof,: and CD80 protein, a fragment thereof, or a variant thereof. Applicant’s argue that it would not have been obvious to one of ordinary skill in the art to derive the claimed fusion protein from the combination of Kong et al, Ast et al., Swanson et al, and Qin et al. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). Additionally, according the MPEP 2145 (IV), “One cannot show nonobviousness by attacking references individually where the rejections are based on a combination of references”. In this case, the combined teachings of Kong et al, Ast et al., Swanson et al, and Qin et al. provide all the teachings and guidance to motivate one of ordinary skill in the art to arrive at the fusion protein described in claims 1 and 19 as summarized in the rejections above.
However, Applicant has incorporated , in part, previous claims 13 and 33 into amended claim 1 (see pg. 9 and 10). Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of amendment of claim 1 (which claim 19 is dependent on).
(new rejection, necessitated by amendment) Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Kong et al. (Biochem. Cell. Biol. Vol. 85, pg. 685-695) in view of Swanson et al. (US Patent Application Publication US 2019/0135922 A1; May 9, 2019) and in further view of Ast et al. (US Patent No: US 9,266,938 B2; Feb. 23, 2016) as applied to claim 18 above, and further in view of Qin (US Patent No: 9,745,359B2; Aug. 29, 2017) hereinafter referred to as Qin.
The teachings of Kong et al., Swanson et al., and Ast et al. as applied to claim 18 are summarized above.
With regards to claim 19, Kong et al. fail to teach a peptide linker with SEQ NO: 3 (GGGGSAESKYGPPCPPCP). Swanson et al. and Ast et al. also do not specifically teach the use of a GGGGSAESKYGPPCPPCP peptide linker.
Qin teaches a peptide linker, (GGGGSAEKSKYGPPCPPCP), (equivalent to SEQ ID NO:3 of the current instant application) that links the interleukin-1 receptor antagonist protein with an IgG4 Fc (Column 48, lines 10-29).
It would therefore have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to use a GGGGSAEKSKYGPPCPPCP peptide linker as taught by Qin, in order to link IL-2 to the Fc in the above obvious fusions proteins as obvious over the combined teachings of Kong et al., Swanson et al. and Ast et al. The expectation of success would be high based upon the high level of skill in the art in the area of recombinant protein engineering as exemplified by Kong et al., Ast et al., Swanson et al. and Qin who teach all the methods and components that are necessary to produce the obvious mutant fusion with the peptide linker.
(new rejection, necessitated by amendment) Thus claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Kong et al. (Biochem. Cell. Biol. Vol. 85, pg. 685-695) in view of Swanson et al. (US Patent Application Publication US 2019/0135922 A1; May 9, 2019) and in further view of Ast et al. (US Patent No: US 9,266,938 B2; Feb. 23, 2016) as applied to claim 18 above, and further in view of Qin (US Patent No: 9,745,359B2; Aug. 29, 2017).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
(previous rejection, withdrawn) Claim 2 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 2 of U.S. Patent No. US11639383 B2 to Jang et al., hereinafter referred to as ‘383.
.
(previous rejection, withdrawn) Claims 5 and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of ‘383
(previous rejection, withdrawn) Claim 10 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 3 of ‘383.
(previous rejection, withdrawn) Claim 22 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of ‘383.
Response to Arguments
Applicant’s arguments, see pg. 8, 13, filed 04/02/2026, with respect to claims 2, 5, and 22 have been fully considered and are persuasive. Applicant has amended claim 1 to incorporate, in part, previous claims 13 and 33. Applicant has canceled claims 10-11 rending the rejection moot. The rejection of 01/02/2026 has been withdrawn.
(previous rejection, withdrawn) Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US12478675B2 to Jang et al., hereinafter referred to as ‘675.
(previous rejection, withdrawn) Claim 2 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 2 of ‘675.
(previous rejection, withdrawn) Claim 3 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 3 of ‘675.
(previous rejection, withdrawn) Claim 4 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of ‘675.
(previous rejection, withdrawn) Claim 5 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 5 of ‘675.
(previous rejection, withdrawn) Claim 6 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6 of ‘675.
(previous rejection, withdrawn) Claim 7 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 7 of ‘675.
(previous rejection, withdrawn) Claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of ‘675.
(previous rejection, withdrawn) Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 9 of ‘675.
(previous rejection, withdrawn) Claim 10 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 11 of ‘675.
(previous rejection, withdrawn) Claim 14 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 12 of ‘675.
(previous rejection, withdrawn) Claim 15 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 13 of ‘675
(previous rejection, withdrawn) Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 14 of ‘675.
Claim 17 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of ‘675.
(previous rejection, withdrawn) Claim 18 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16 of ‘675.
(previous rejection, withdrawn) Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17 of ‘675.
(previous rejection, withdrawn) Claim 20 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 18 of US Patent No. US124786753B2.
Response to Arguments
Applicant’s arguments, see pg. 8 and 13, filed 04/02/2026, with respect to claims 1-8, and 14-20 have been fully considered and are persuasive. Applicant has canceled claims 9-10 thus rendering the rejection moot. The rejection of 01/02/2026 has been withdrawn.
(previous rejection, withdrawn) Claim 3 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 3 of US Patent No. US11492384B2 to Jang hereinafter referred to as ‘384.
(previous rejection, withdrawn) Claim 4 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of ‘384.
(previous rejection, withdrawn) Claim 5 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 5 of ‘384.
(previous rejection, withdrawn) Claim 6 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6 of ‘384.
(previous rejection, withdrawn) Claim 7 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 7 of ‘384.
(previous rejection, withdrawn) Claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of ‘384.
(previous rejection, withdrawn) Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 9 of ‘384.
(previous rejection, withdrawn) Claim 15 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 12 of ‘384.
(previous rejection, withdrawn) Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 13 of ‘384.
(previous rejection, withdrawn) Claim 17 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 14 of ‘384
(previous rejection, withdrawn) Claim 18 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of ‘384.
(previous rejection, withdrawn) Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of ‘384.
(previous rejection, withdrawn) Claim 20 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16 of ‘384.
(previous rejection, withdrawn) Claim 22 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17 of ‘384
(previous rejection, withdrawn) Claim 23 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 18 of ‘384
(previous rejection, withdrawn) Claim 24 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 19 of ‘384.
Response to Arguments
Applicant’s arguments, see pg. 8 and 13, filed 04/02/2026, with respect to claims 3-8, 15-20, 22-24 have been fully considered and are persuasive. Applicant has amended claim 1 to incorporate, in part, previous claims 13 and 33. Applicant has canceled claim 9 rendering the rejection moot. The rejection of 01/02/2026 has been withdrawn.
(previous rejection, withdrawn) Claims 1,3,7,11, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of US Patent No. US11857601B2 to Jang et al., hereinafter referred to as ‘601.
Response to Arguments
Applicant’s arguments, see 8 and 13, filed 04/02/2026, with respect to claims 1, 3, 7, 11, and 18 have been fully considered and are persuasive. Applicant has canceled claim 11 rendering the rejection moot. The rejection of 01/02/2026 has been withdrawn.
(previous rejection, withdrawn) Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17912398 (Jang et al.) hereinafter referred to as ‘398.
Response to Arguments
Applicant’s arguments, see 8 and 13, filed 04/02/2026, with respect to claim 1 have been fully considered and are persuasive. Applicant has amended claim 1 to incorporate, in part, previous claims 13 and 33. The rejection of 01/02/2026 has been withdrawn.
(previous rejection, withdrawn) Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 2 of copending Application No. 18499840 (Jang et al.) hereinafter referred to as ‘840.
(previous rejection, withdrawn) Claims 1, 4, 5, 7, and 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending ‘840
(previous rejection, withdrawn) Claim 7 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of copending ‘840.
(previous rejection, withdrawn) Claim 6 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16 of copending ‘840.
Response to Arguments
Applicant’s arguments, see 8 and 13, filed 04/02/2026, with respect to claim 1, 2, 4, 5, 6, and 7 have been fully considered and are persuasive. Applicant has amended claim 1 to incorporate, in part, previous claims 13 and 33. Applicant has canceled claim 11 thus rendering the rejection moot. The rejection of 01/02/2026 has been withdrawn.
(previous rejection, withdrawn) Claim 4 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 3 of copending Application No. 17948894 hereinafter referred to as ‘894.
(previous rejection, withdrawn) Claim 5 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of copending ‘894.
(previous rejection, withdrawn) Claim 7 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6 of copending ‘894.
(previous rejection, withdrawn) Claim 8 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 7 of copending ‘894.
(previous rejection, withdrawn) Claim 10 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 9 of copending ‘894.
(previous rejection, withdrawn) Claims 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 12 of copending ‘894.
(previous rejection, withdrawn) Claim 22 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17 of copending ‘894.
(previous rejection, withdrawn) Claim 24 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16 of copending ‘894.
Response to Arguments
Applicant’s arguments, see 8 and 13, filed 04/02/2026, with respect to claims 4-5, 7-8, 19-20, 22, 24 have been fully considered and are persuasive. Applicant has amended claim 1 to incorporate, in part, previous claims 13 and 33. Applicant has canceled claim 10 thus rendering the rejection moot. The rejection of 01/02/2026 has been withdrawn.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE T LOUNTOS whose telephone number is (571)272-0502. The examiner can normally be reached Monday-Friday 8:00 am - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Mondesi can be reached at 408-918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/GEORGE THEMISTOCLIS LOUNTOS/ Examiner, Art Unit 1652
/ROBERT B MONDESI/ Supervisory Patent Examiner, Art Unit 1652
Prosecution Insights