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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/21/2026 has been entered.
Claim Status
Claims 7-8 and 16-18 have been cancelled; claims 1, 11, and 19-20 have been amended; and claims 23-24 have been newly added, as requested in the amendment filed on 05/21/2026. Following the amendment, claims 1-6, 9-15, and 19-24 are pending in the instant application.
Claim 21 stands as withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected subject matter in the Response filed 04/02/2025, there being no allowable generic or linking claim.
Claims 1-6, 9-15, 19-20, and 22-24 are under examination in the instant office action.
Claim Interpretation
With regard to sequence language, the following are noted:
The recitation of, for example, “comprises the amino acid sequence of SEQ ID NO: 85” is being interpreted such that for a reference sequence to meet the limitation, it must comprise/consist of full-length SEQ ID NO: 85. This interpretation pertains to claims 1 and 12.
The recitation of, for example, “the linker 3 is selected from a group consisting of SEQ ID NOs: 59 to 90” is being interpreted such that for a reference sequence to meet the limitation, it must comprise/consist of one of full-length SEQ ID NOs: 59 to 90. This interpretation pertains to claims 4 and 20.
The recitation of, for example, “comprises an amino acid sequence selected from a group consisting of SEQ ID NOs: 104 to 110” is being interpreted such that for a reference sequence to meet the limitation, it must comprise/consist of one of full-length SEQ ID NOs: 104 to 110. This interpretation pertains to claims 5-6 and 23-24.
Art-Free Subject Matter
It is noted that the instantly elected species of bispecific antibody comprising (i) the fusion heavy chain comprising SEQ ID NOs: 41, 111, 85, 59, 74, 91, 117, and 120 and the fusion light chain comprising SEQ ID NOs: 42, 104, 85, and 60; or (ii) the fusion heavy chain comprising SEQ ID NOs: 41, 111, 85, 60, 74, 91, 117, and 120 and the fusion light chain comprising SEQ ID NOs: 42, 104, 85, and 59 (see claim 12(7) and 12(20)) have been thoroughly searched and are free of the prior art. Additionally, it is noted that a CH2 domain comprising full-length SEQ ID NO: 117 (see claim 23) has also been searched and is also free of the prior art. However, claims 1 and 19, from which claims 12 and 23 respectively depend, are rejected as detailed below. As such, claims 12 and 23 are objected to for being dependent upon a rejected claim.
Specification - Objection Withdrawn
It is noted that Applicant has provided a substitute specification wherein to revert the definitions of Kabat CDRs H3 and L3 that as in the original specification filed and add sequence identifier “WGXG” in the definitions of Kabat CDRs H3 and L3, wherein the sequence listing paragraph is also updated accordingly. Thus, the objection to the specification regarding new matter is withdrawn.
Claim Objections - Withdrawn
Claims 7-8, 11, and 19-20 were objected to for minor informalities. Applicant has cancelled claims 7-8, rendering their objection moot. Claim 11 has been amended to replace “and” with “or”. Claim 19 has been amended such that VHb and VLb are consistently used. Claim 20 has been amended to replace “or” with “and”. As such, the objections to claims 7-8, 11, and 19-20 are withdrawn.
Claim Objections - New
Claim 24 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Objections - Maintained
Claims 12 stands as objected to for depending on a rejected claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112 - Improper Markush - Withdrawn
Claims 9-12 were rejected on the basis that it contains an improper Markush grouping of alternatives.
Applicant’s arguments, see Page 18 of Remarks, filed 05/21/2026, with respect to the rejection of claims 9-12 as containing an improper Markush grouping of alternatives have been fully considered and are persuasive. The rejection of claims 9-12 as containing an improper Markush grouping of alternatives is withdrawn.
Claim Rejections - 35 USC § 103 - Withdrawn
Claims 7-8 were rejected under 35 U.S.C. 103 as being unpatentable over US 2013/0115215 (previously cited on PTO-892; herein after referred to as “Zhou”) in view of US 2009/0155275 (previously cited on PTO-892; herein after referred to as “Wu”), US 2002/0052480 (previously cited on PTO-892: herein after referred to as “Park”), US 2005/0260716 (previously cited on PTO-892; herein after referred to as “Moore”), US 2004/0102369 (previously cited on PTO-892; herein after referred to as “Pardridge”), US 2014/0370019 (previously cited on PTO-892; herein after referred to as “Bruenker”), US 2017/0355770 (previously cited on PTO-892; herein after referred to as “Wang”), US 2002/0176858 (previously cited on PTO-892; herein after referred to as “Dasch”), and CN 104693270 (previously cited on PTO-892; translation previously provided; herein after referred to as “Huang”).
Claims 7-8 have been cancelled, rendering their rejection moot. As such, the rejection of claims 7-8 under 35 U.S.C. 103 as being unpatentable over the above-cited references is withdrawn.
Claim Rejections - 35 USC § 103 - Maintained
Claims 1-6, 9-11, 13-15, 19-20, and 22 stand as rejected, and new claim 24 is newly rejected, under 35 U.S.C. 103 as being unpatentable over US 2013/0115215 (previously cited on PTO-892; herein after referred to as “Zhou”) in view of US 2009/0155275 (previously cited on PTO-892; herein after referred to as “Wu”), US 2002/0052480 (previously cited on PTO-892: herein after referred to as “Park”), US 2005/0260716 (previously cited on PTO-892; herein after referred to as “Moore”), US 2004/0102369 (previously cited on PTO-892; herein after referred to as “Pardridge”), US 2014/0370019 (previously cited on PTO-892; herein after referred to as “Bruenker”), US 2017/0355770 (previously cited on PTO-892; herein after referred to as “Wang”), US 2002/0176858 (previously cited on PTO-892; herein after referred to as “Dasch”), and CN 104693270 (previously cited on PTO-892; translation previously provided; herein after referred to as “Huang”).
Claims 1-6, 9-11, 13-15, 19-20, and 22 stand as rejected for reasons already of record.
Regarding new claim 24, it is specifically noted that above-listed combination of references as presented in the Office Action dated 12/01/2025 renders obvious new claim 24. Claim 19 was previously rendered obvious by the above-recited combination of references. Regarding new claim 24, it is noted that Pardridge teaches a human CH3 in their SEQ ID NO. 4 which comprises instant SEQ ID NO. 120 (0023).
Thus, human versions of CH3 as required by new claim 24 was well-known to the prior art and so it would be prima facie obvious to use the human CH3 domain disclosed by Pardridge in the obvious bispecific antibody of claim 19, wherein the general structure of the bispecific antibody/tetravalent symmetrical bispecific antibody would be arrived at specifically from the combined teachings of Zhou, Wu, Bruenker, and Huang. These obvious molecules require CH3 domains, and substitution of one such domain for another will yield predictable results. Furthermore, use of human versions carries the advantage of facilitating the therapeutic antibodies evasion of the human immune system, promoting patient treatment therewith owed to longer half-life.
Response to Arguments - 35 USC § 103
Applicant's arguments filed 05/21 (herein after referred to as “Remarks”; see Pages 11-18, specifically) have been fully considered but they are not persuasive.
With regard to the argument that one of ordinary skill in the art would not have been motivated to select Huang SEQ ID NO: 9 (corresponding to instant SEQ ID NO: 85), 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). In this case, Huang teaches a linker peptide for fusion proteins (0014-0015) which can be their SEQ ID NO. 9 (0020), wherein Page 22 of the original, untranslated document shows that this sequence is a 100% match to instant SEQ ID NO. 85. A linker peptide for fusion proteins, like the bispecific antibody rendered obvious, save for instant SEQ ID NO. 85, was well-known prior to filing of the instant application. Thus, it is maintained that it would have been obvious to a PHOSITA to use it as any of the linkers in the obvious antibody since such is a fusion protein and the sequence can function as a linker in such a context. The use of Huang SEQ ID NO. 9 in such an obvious antibody construct is merely substitution of one known linker from the art with that of Huang to arrive at predictable results, a successfully produced and functional bispecific antibody against human PD-L1 and human TGFbeta.
With regard to the arguments of unexpected results regarding antibody expression level, purity, and stability (under thermal and acidic conditions), the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Furthermore, MPEP 716.02b recites that evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) (Mere conclusions in appellants’ brief that the claimed polymer had an unexpectedly increased impact strength "are not entitled to the weight of conclusions accompanying the evidence, either in the specification or in a declaration."); Ex parte C, 27 USPQ2d 1492 (Bd. Pat. App. & Inter. 1992) (Applicant alleged unexpected results with regard to the claimed soybean plant, however there was no basis for judging the practical significance of data with regard to maturity date, flowering date, flower color, or height of the plant.). See also In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977) and In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) as discussed in MPEP § 716.02(c). It is specifically noted that there is no statistical analysis for any of the data presented in Tables A-C, wherein bispecific antibody constructs wherein Linker 1 and Linker 2 are both lin17 are argued as “significantly better” and “markedly improved”. Thus, absent statistical analysis to support such conclusions, the differences in the presented results are not of both statistical and practical significance and are not supportive of nonobviousness.
Conclusion
Claims 1-6, 9-15, and 19-24 are pending. Claim 21 is withdrawn. Claims 1-6, 9-11, 13-15, 19-20, 22, and 24 are rejected. Claims 12 and 23 are objected to. No claims are allowed.
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/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642
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