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 .
Claim Status
Claim listing filed on August 8, 2025 is pending. Claims 1-24 and 31 are canceled. Claims 33-43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected species in the election filed on April 9, 2025. Claims 25-30 and 32 are examined upon their merits.
Withdrawn Objections and Rejections
Applicant’s cancelation of Claim 31 has rendered all previous rejections directed to this claim moot.
Applicant’s amendments to the specification have overcome all objections of record, and the specification objections are withdrawn.
The rejection of claims 25-30 and 32 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of applicant’s amendments. In particular, Claim 25 now recites specific amino acid structures which overcome the indefinite functional language.
The rejection of claims 25-30 and 32 under 35 U.S.C. 112(a) as failing to comply with the written description and enablement requirements is withdrawn in view of applicant’s amendments. In particular, Claim 25 now recites specific amino acid structures and is no longer directed to a genus of possible TGF-β traps.
The rejection of Claims 25-27, 29-30, and 32 under 35 U.S.C. 103 as being unpatentable over Kumar et al. WO 2018/204594 in view of Lo US 2015/0225483 is withdrawn in view of applicant’s amendments. Kumar and Lo do not teach the specific amino acid sequences required by amended Claim 25.
Claim Rejections - 35 USC § 112 (New, necessitated by amendment)
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.
Claim 32 is 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.
Claim 32 depends from Claim 25 and recites wherein a peptide signal sequence is fused to the amino terminus of the trap. However, Claim 25 defines wherein the trap comprises SEQ ID NOs: 17 or 23 which both comprise a signal sequence at the amino terminus (SEQ ID NO: 5). It is unclear if Claim 32 encompasses fusing a second peptide signal sequence onto the amino terminus of SEQ ID NOs: 17 and 23 or if Claim 32 is describing the signal peptides already present on SEQ ID NOs: 17 and 23. The specification defines that a singular signal peptide at the amino terminus of the trap directs the newly synthesized protein into the secretory pathway of the host cell, and the signal peptide is cleaved from the rest of the protein during secretion to produce the mature trap protein (paragraph [029]). Therefore, the specification teaches one signal peptide per trap protein, but as written, Claim 32 could comprise fusing a second signal peptide onto the first signal peptides of SEQ ID NOs: 17 and 23. Claims 32 is rejected for indefiniteness.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 27 and 30 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 27 depends from Claim 25 and recites wherein said ligand-binding domain of TGFβRII is linked to the carboxy-terminus of said Fc domain via a linker moiety. Claim 25 defines wherein the trap comprises SEQ ID NOs: 23 or 25. SEQ ID NOs: 23 and 25 comprise the orientation TGFBRII - (G4S)25 Poly Linker - C27S Hinge - IgG1 Fc (sequence listing) which has the TGFβRII linked to the amino-terminus of the Fc domain, not the carboxy-terminus. Therefore, Claim 27 fails to include the limitations of Claim 25 on which it depends.
Claim 30 depends from Claim 25 and recites wherein said linker comprises five G4S repeats. Claim 25 defines wherein the trap comprises SEQ ID NOs: 17 or 24. SEQ ID NOs: 17 and 24 only comprise four G4S repeats (sequence listing). Therefore, Claim 30 fails to include all the limitations of Claim 25 on which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103 (Maintained)
The rejection of Claims 25-30 and 32 under 35 U.S.C. 103 as being unpatentable over Kumar et al. WO 2018/204594 (of record) in view of Lo US 2015/0225483 (of record), and further in view of Li et al. US 11,168,138 (of record) is maintained. Note, the previous rejection applied to Claims 25-27 and 29-32 and now applies to Claims 25-30 and 32 due to Applicant’s amendments.
Applicant's arguments filed August 8, 2025 have been fully considered but they are not persuasive.
Applicant argues that a patent is not proved obvious merely by demonstrating that each of its elements was independently known in the prior art, and the Examiner must identify a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements. However, the Applicant cited case law without distinctly and specifically pointing out the supposed errors in the Examiner’s action as is required in a complete response (MPEP § 714.02). Therefore, these arguments do not warrant a complete response and are not persuasive.
Applicant argues that the claimed invention is nonobvious due to unexpected results. Applicant argues while Lo teaches hinge region mutations as a way to avoid incorrect disulfide bonding, it does not suggest the disclosed data of Figures 1-3 that teach that the modified hinge region was more effective than the unmodified hinge region. These arguments are not persuasive for two reasons. First, Figures 1-3 compare a trap comprising an unmodified hinge region and a sushi domain versus a trap comprising a modified hinge region and no sushi domain. Two variables are altered between the traps (both the hinge domain and the presence of a sushi domain). Because two variables were varied at the same time, it cannot be determined from the data in Figures 1-3 that the resulting effect was due to the modified hinge region and not an effect of the absence of a sushi domain. The second reason that Applicant’s arguments are not persuasive is that the results would not be considered unexpected by one of ordinary skill in the art prior to the time of filing. Vaniotis et al. Sci Rep. 2018 teaches that cysteine-serine substitutions in the Fc hinge region of IGF-TRAP eliminated high-molecular-weight oligomerized species (abstract), and the traps with modified hinge regions had increased efficacy likely due to improved purity (Discussion paragraph 1). Thus, it was understood in the art prior to filing that substituting cysteine to serine in the Fc hinge region avoids unwanted protein aggregates caused by unintended disulfide binding and can improve efficacy by improving purity of the intended protein product. The instant invention is obvious over the teachings of Kumar, Lo, and Li, and the instant results are not unexpected in view of the state of the art prior to filing. Note, Vaniotis was cited solely to reply to Applicant’s argument and not as a new grounds of rejection.
Applicant argues that the combination of the cited prior art does not teach every claimed trap as required by amended Claim 25 (SEQ ID NOs: 17, 24, 23, and 25). Examiner maintains that Claim 25 is directed to a trap comprising SEQ ID NOs: 17, 24, 23, or 25. Thus, prior art that obviates one of the sequences reads on the entire claim.
Applicant argues that the teachings of Lo apply to the hinge region of IgG2 wherein the instant traps comprise hinge regions of IgG1. Examiner maintains that Applicant is taking the quotation from Lo paragraph [0160] out of context of the paragraph as a whole. Paragraph [0160] discusses mutating unpaired cysteine residues in IgG1, IgG2, and IgG4 hinge regions citing that the unpaired cysteine residues in the various hinge regions are known to promote oligomerization, incorrect disulfide bonding during secretion in recombinant systems, and inefficient interchain disulfide bonds. It would be obvious to one of ordinary skill that these problems caused by unpaired cysteine residues span across IgG types. Paragraph [0160] further outlines specific mutations for IgG1 hinges, IgG2 hinges, and IgG4 hinges that can overcome the problem of unpaired cysteine residues. Of all the IgG types, paragraphs [0160] and [0158] teach that the hinge region of IgG1 with a cysteine to serine mutation is most preferred. Applicant’s arguments are not found persuasive, and the rejections are maintained.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 SARAH COOPER PATTERSON whose telephone number is (703)756-1991. The examiner can normally be reached Monday - Friday 8:00am - 5:00pm EST.
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/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675