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 Applicant’s election without traverse of Group I (claims 1-30 , and linking claims 31-34 ) comprising the species of (1) PD-1 polypeptide comprising PD1 construct 4XMUT_M70 (SEQ ID NO: 54), (2) the IgG4 Fc fusion of this construct (SEQ ID NO: 56), and (3) the same construct further comprising tEGFR (SEQ ID NO: 90), in the reply filed on 23Jan2026 is acknowledged. Claim (s) 35-38 is/are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention , there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 23Jan2026 . Claim(s) 1-3 4 is/are currently pending and presented for examination on the merits. Specification The use of trade name(s) or mark(s) used in commerce (e.g., FlowJo , BioLegend , Invitrogen, Cell Signaling Technology, BD ), has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term . Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (e.g., pg. 10, line 9; pg. 64, line 1) . Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Claim Interpretation Regarding the elected PD1 decoy species, the wild-type (WT) PD1 decoy (SEQ ID NO: 6) sequence was aligned with the instant elected PD1 decoy of SEQ ID NO: 54 (see alignment below). Based on the alignment, SEQ ID NO: 54 comprises T76D, K78R, L122F, and Q133K substitutions (relative to full length WT PD1, see 112(b) rejection below for details). Therefore, prior art disclosing WT PD1 with at least T76D, K78R, L122F, and Q133K substitutions will be considered to meet the limitations of instant SEQ ID NO: 54. Alignment of instant PD1 decoy polypeptide of SEQ ID NO: 6 and elected species of PD1 decoy polypeptide of SEQ ID NO: 54: CLUSTAL O(1.2.4) multiple sequence alignment Seq6 MASDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQ T D K LAAF 60 Seq54 MASDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQ D D R LAAF 60 ***************************************************** *:**** Seq6 PEDRSQPGQDARFRVTQLPNGRDFHMSVVRARRNDSGTY L CGAISLAPKA Q IKESLRAEL 120 Seq54 PEDRSQPGQDARFRVTQLPNGRDFHMSVVRARRNDSGTY F CGAISLAPKA K IKESLRAEL 120 ***************************************:**********:********* Seq6 RVTERRALE 129 Seq54 RVTERRALE 129 ********* Claim Rejections - 35 USC § 112 (b) The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. 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 (s) 1-34 is/are 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. Regarding claim(s) 1-34, the phrase “has at least 80% identity to SEQ ID NO: 6 and comprises substitutions at least at positions T76 , K78, and Q133 of SEQ ID NO: 6” in lines 2-3 of claim 1 renders the claim ( s ) indefinite. Specifically, it is unclear if the phrase means that the (1) PD1 variant shares at least 80% sequence identity with SEQ ID NO: 6, not including the T76, K78, and Q133 substitutions; (2) PD1 variant shares at least 80% sequence identity with SEQ ID NO: 6, including the T76, K78, and Q133 substitutions; or (3) something else. For the purposes of compact prosecution, the phrase is considered to mean that the ‘ at least 80% sequence identity ’ does not include the T76, K78, and Q133 substitutions . This rejection may be overcome by amending claim 1 to clearly recite the limitations of the instant invention. Claims 2-34 can overcome this rejection by amending claim 1 as described above. Regarding claim(s) 1-34, the phrase “comprises substitutions at least at positions T76, K78, and Q133 of SEQ ID NO: 6 ” in line 3 of claim 1 renders the claim(s) indefinite. Specifically, (1) residue 78 is a leucine (e.g., L) not a lysine (e.g., K), and (2) the sequence terminates with residue 129, and therefore there is no residue 133 (see sequence below). Applicant was made aware of this discrepancy as a “formal matter” in the prior office action mailed on 23Jan2026. Applicant responded to this formal matter stating in summary that a P H OSITA would understand that the PD1 sequence of SEQ ID NO: 6 does not contain a 22-residue signal peptide found in the complete wild-type sequence , and therefore a PHOSITA would understand that SEQ ID NO: 6 should be considered to start with residue 23. However, the plain claim language clearly recites that the instant invention “ comprises substitutions at least at positions T76, K78, and Q133 of SEQ ID NO: 6 ”. Therefore, given the plain language of the claim, one would expect those substitutions to be at the specified residues of SEQ ID NO: 6 . For the purposes of compact prosecution, the substitutions of positions in claim 1 and all dependent claims are considered to be relative to the full WT PD1 sequenc e , as disclosed in Applicant Fig. 4 and d escription of the drawings. Applicant may overcome this rejection by amending claim 1 to recite (1) “ at positions T76, K78, and Q133 relative to full length wild-type PD1 comprising a 22-residue signal peptide of SEQ ID NO: 6 ” ; (2) “comprises substitutions at least at positions T76, K78, and Q133 of SEQ ID NO: 6 , wherein the first residue of SEQ ID NO: 6 is position number 23 ”; or ( 3 ) to otherwise clearly recite the limitations of the instant invention. Claims 2-34 can overcome this rejection by amending claim 1 as described above. Instant PD-1 variant (SEQ ID NO: 6): Residue Key: Residue 76 ; Residue 78 SeqID_6 MASDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAF 60 SeqID_6 PEDRSQPGQDARFRV T Q L PNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAEL 120 SeqID_6 RVTERRALE 129 Claim(s) 4, recite(s) the limitation “wherein the additional substitutions comprise at least one of” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. For the purposes of compact prosecution the phrase “wherein the additional substitutions comprise at least one of” is considered to read “wherein the substitutions further comprise one or more additional substitutions compris [[e]] ing at least one of”. This rejection may be overcome by amending claim 4 to provide proper antecedent basis. Claim(s) 5-6, recite(s) the limitation “comprises the substitutions” in line 2 claims 5 and 6. There is insufficient antecedent basis for this limitation in the claim. For the purposes of compact prosecution the phrase “comprises the substitutions” is considered to read “comprises substitutions ”. This rejection may be overcome by amending claims 5-6 to provide proper antecedent basis. Regarding claim(s) 5-6, the phrase “substitutions at the positions… E122 …” in line 2 of claims 5 and 6 renders the claim indefinite. Specifically, the residue at position 122 (see 112(b) rejection above for details) is a L residue in SEQ ID NO: 6, not a E residue. For the purposes of compact prosecution, “E122” in the phrase above is considered to mean “L122”. Regarding claim(s) 10, the phrase “comprises (a) a CH3 domain; and (b) part or whole of an Fc region” in lines 1-2 renders the claim indefinite. A skilled artisan would understand Fc regions comprise a CH3 domain. Therefore, it is unclear if (1) a single CH3 domain would meet the limitations of (a-b) simultaneously; (2) if the phrase requires CH3 in addition to any part or whole of an Fc domain; (3) if the ‘part’ of an Fc region comprises only an Fc domain know in the art (e.g., CH1, CH2, CH3); (4) if the ‘part’ of an Fc domain comprises an unknown number of amino acids of an Fc region (e.g., 45 residues, 20 residues, 10 residues, 1 residue); or (5) something else. For the purposes of compact prosecution, a single CH3 domain is considered to meet all of the limitations of the phrase “comprises (a) a CH3 domain; and (b) part or whole of an Fc region”. This rejection may be overcome by amending claim 10 to clearly recite the limitations of the invention. Claim Rejections - 35 USC § 103 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 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 . This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claim(s) 1 -2, 5-6, 8-10, 17-18, 20-22, and 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2023/0131056 A 1 (hereinafter “US056”) . Regarding instant claim(s) 1 -2, 5-6, 8-10 , US506 teaches that PD 1 variant-Fc fusion proteins can alleviate or reverse inhibition of the adaptive immunity in patients with cancer or an infection [ e.g., ¶ 0009 ] . US056 teaches PD1 variant -Fc fusion proteins comprising a WT PD 1 sequence with one to eight PD1 residue substitutions [ e.g., title, abstract; ¶ 040 , ; tbls . 6-7, 10 ] , and teaches possible residue substitutions comprising positions T76, K78, L122, A132, and Q133 [ e.g., tbl . 6 ] . US056 teaches the Fc fusion partner comprises hIgG4 comprising from one to twenty substitutions [ e.g., ¶ 132-134 , 136, 140, 187-0196 ] . US056 further teaches that examples set forth are provided to give skilled artisans a complete disclosure and description of how to make and use the embodiments of the compositions, systems, and methods of the invention, and are not intended to limit the scope of what the inventors regard as their invention(s), and that obvious modifications are within the scope of claims [ e.g., ¶ 0487 ] . US056 further teaches that all headings and section designations are used for clarity and reference purposes only and are not to be considered limiting in any way, giving the example that a skilled artisan would appreciate the usefulness of combining various aspects from different headings and sections as appropriate [ e.g., ¶ 0488 ] . Regarding instant claim(s) 17 , US056 further teaches the PD1 variant-Fc fusion protein comprises a detectable label [ e.g., ¶ 0082, 0456 ] . Regarding instant claim(s) 18 , 20-21 , US056 further teaches a host cell comprising a vector comprising a polynucleotide encoding the PD1 variant-Fc fusion protein [ e.g., ¶ 0050-0052, 0388-03 98 ] . Regarding instant claim(s) 22 , 24 , US056 further teaches a single vector or plasmid or two or more vectors or plasmids that contain the total DNA to be introduced into the genome of the host cells [ e.g., ¶ 0393 ] . Regarding instant claim(s) 31 , US056 further teaches a pharmaceutical composition comprising the PD1 variant-Fc fusion polypeptide [ e.g., ¶ 120 ] . US056 does not expressly teach ( 1 ) a PD1 variant - hIgG4 Fc fusion protein wherein the PD1 variant comprises T76, K78, L122, A132, and Q133 substitutions and wherein (a) the fusion protein further comprises a detectable label; or (2) a host cell compri sing one or more vector s comprising a one or more polynucleotide (s) encoding the fusion protein . It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) to make multiple substitutions comprising at least positions T76, K78, L122, A132, and Q133 in the PD1 variant of the PD1 variant- hIgG4 Fc fusion protein as taught by US056 to arrive at the instant invention of a PD1 variant-Fc fusion protein, wherein the PD1 variant comprises at least T76, K78, L122, A132, and Q133 substitutions . This conclusion of obviousness is based on the 'obvious to try rationale'. A PHOSITA would have been motivated to try because US506 teaches PD1 variant-Fc fusion proteins are effective therapies that can alleviate or reverse inhibition of the adaptive immunity in patients with cancer or an infection. There are only 29 possible individual substitutions disclosed by US056 for PD1 modifications to create PD1 variants. Additionally , while US056 only teaches one to 8 substitutions in a PD1 variant, US056 further teaches that additional modifications not expressly disclosed are within the scope of their invention and that the variants expressly disclosed are non-limiting examples (see rejection above for details). Further, as instant SEQ ID NO: 6 comprises 129 amino acids, a skilled artisan could substitute 26 (e.g., all but 3 disclosed by US056 ) and still be within 80% sequence identity to SEQ ID NO: 6. Further still, based on the wording of the instant claim s , all 29 substitutions disclosed by US056 could be made to instant SEQ ID NO: 6 and still meet the limitation(s) thereof (see 112(b) rejection above for details). Therefore, not only would all US056 -disclosed PD1 variant substitutions read on the instant invention, but it would also be obvious for a skilled artisan to try various combinations of one to eight PD1 substitutions not expressly tested in US056 to determine which combination(s) are optimal, which is well within the purview of those in the art ( as evidenced by US056 disclosure, see above ). This rationale aligns with choosing from a finite number of identified, predictable solutions with a reasonable expectation of success; see MPEP 2143(I)(E). Further, it would have been obvious to a PHOSITA to modify the modified PD1 variant-hIgG4 Fc fusion protein wherein the PD1 variant comprises T76, K78, L122, A132, and Q133 of US056 (see above) to include that (1) the fusion protein further comprises a detectable label; and/or (2) a host cell comprising one or more vectors comprising a one or more polynucleotide(s) encoding the fusion protein as taught by US056 , because all of the modifications are disclosed within the single US056 reference, US056 indicates combinations not expressly listed are within the scope of their invention(s), and US056 teaches practices common in the art including (1) detectable labeling of the fusion protein , and (2) various compositions for the expression of the fusion protein . There is an expectation of success for a PHOPSITA to add (1) a detectable label to, and/or (2) a compositions for fusion protein expression of the modified PD1 variant-hIgG4 Fc fusion protein wherein the PD1 variant comprises T76, K78, L122, A132, and Q133 as taught by US056 (see above), because the base fusion protein structure is taught by US056 (see above), and US056 further teaches practices common in the art including (1) detectable labeling of the fusion protein, and (2) various compositions for the expression of the fusion protein . This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141). Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary. Free From the Prior Art During the course of examination, while all of the PD1 variant residue substitution position s of the instant claim(s) were disclosed in the prior art , there was no rational specifically found to arrive at a PD1 variant consisting of substitutions at positions (1) T76, K78, and Q133 only; (2) T76, K78, A132, and Q133 only; (3) T76, K78, L122, and Q133 only; or (4) T76, K78, L122, A132, and Q133 only. Specifically, the open language “comprising” of the instant claims doesn’t require only the recited position substitutions (e.g., allowing for additional substitutions and not requiring rationale for selecting only those residues claimed from the list of possible substitution sites in the prior art), but if the current claim language was limited to consisting of only specific substitution(s), they would become non-obvious in view of the prior art. Conclusion No claims are currently allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT AMY M CHATTIN whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-0646 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT T-F 0600-1600 PST . 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, FILLIN "SPE Name?" \* MERGEFORMAT Julie Wu can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571) 272-5205 . 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. /AMY M. CHATTIN/ Examiner, Art Unit 1643 /GARY B NICKOL/ Primary Examiner, Art Unit 1643