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 .
Election/Restrictions
Applicants’ election of Species A (i.e., Single and specific chain trimer (SCT) including indication of: 1. Single and specific first linker, indicating single and specific percent homology to a single and specific sequence identification number, Applicants’ election: GCGGSGGGGSGGGGS (SEQ ID NO: 1); 2. Single and specific amino acid substitution present in the major histocompatibility complex (MHC) I alpha chain, Applicants’ election: {Y84C}; and 3. Single and specific leader peptide, indicating single and specific percent homology to a single and specific sequence identification number, Applicants’ election: SUC2 (SEQ ID NO: 19)), in the reply filed on 10/09/2025 is acknowledged.
During a telephonic communication on 11/06/2025with Applicants’ representative (i.e., Adam Schoen), the percent homology/identity of the elected sequences was confirmed. Applicants election of a first linker that is at least about 90% homologous to SEQ ID NO: 1, as well as a leader peptide that shares 95% or greater sequence identity with SEQ ID NO:19, is acknowledged.
Claims 5-8,11 and 16-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Because Applicants did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Upon searching the elected species (i.e., Single and specific leader peptide, indicating single and specific percent homology to a single and specific sequence identification number, Applicants’ election: SUC2 (SEQ ID NO: 19)), additional species were found, e.g., PH05. Accordingly, for purposes of compact prosecution, the election of species is modified only to the extent of examining this additional species. Otherwise the election of species requirement is still retained.
Priority
The present application claims the benefit under 35 U.S.C 119 (e) to U.S. Provisional Application No. 62/980,088 filed 02/21/2020; and claims status as a 371 (National Stage) of PCT/US2021/018949 02/21/2021.
Claim Status
Claims 1-51 were originally filed and amended on 08/19/2022. The amendment cancelled claims 25-51, and amended claims 3-9, 12-14, 16, 18-19 and 21-24.
The amendment filed on 05/28/2026, amended claim 1, and cancelled claims 2-4, 9-10 and 13-15.
Claims 1, 5-8, 11-12 and 16-24 are pending; and claims 1, 12 and 18-24 are under consideration.
Claim Interpretation/Sequence Interpretation
For purposes of applying prior art, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation set forth below, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
For claim 1, regarding the scope of “portion”, it is noted that the instant specification does not define what constitutes “a portion”. Rather the instant specification teaches that a “functional portion” or a “functional fragment” refers to a polypeptide or polynucleotide that comprises only a domain, motif, portion, or fragment of a parent or reference compound and the polypeptide or encoded polypeptide retains at least 50% activity associated with the domain, portion, or fragment of the parent or reference compound (see instant specification, pg. 19, lines 19-22). As such, the Examiner is interpreting the phrase “at least a portion…” as a functional portion of a parent reference compound that retains at least 50% activity.
For claim 21, the Examiner is interpreting the scope of the leader peptide as sharing 95% or greater percent identity to SEQ ID NO: 19. Since SEQ ID NO: 19 is nineteen amino acids in length; a sequence that shares 95% or greater percent identity would encompass at least 1 modification including any substitution, insertion, deletion, etc.
New Claim Objection
Claim 1 is objected to because of the following informalities: Grammar. The claim includes the phrase “..comprising of …” The preposition “of” is not needed because the term “comprising” describes the relationship between a whole and its parts, therefore “of” makes the term redundant. Appropriate correction is required.
Response to Arguments
1. Applicants’ arguments, see Remarks, filed 05/28/2026, with respect to the 35 U.S.C 112(b) rejection (i.e., ambiguity due to “consisting essentially of”), have been fully considered and are persuasive. The 35 U.S.C 112(b) rejection of claims 1-4, 9-10, 12-15, 18-24 has been withdrawn.
2. Applicants’ arguments, see Remarks, filed 05/28/2026, with respect to the 35 U.S.C 112(b) rejection (i.e., amino acid substitution {Y84C}), have been fully considered and are persuasive. The 35 U.S.C 112(b) rejection of claim 10 is moot.
3. Applicants’ arguments, see Remarks, filed 05/28/2026, with respect to the 35 U.S.C 112(b) rejection (i.e., amino acid substitution {G2C}), have been fully considered and are persuasive. The 35 U.S.C 112(b) rejection of claim 13 is moot.
4. Applicants’ arguments, see Remarks, filed 05/28/2026, with respect to the 35 U.S.C 112(b) rejection (i.e., disulfide bridge between 1st linker and MHC I α chain), have been fully considered and are persuasive. The 35 U.S.C 112(b) rejection of claims 14-15 is moot.
5. Applicants’ arguments, see Remarks, filed 05/28/2026, with respect to the 35 U.S.C 112(b) rejection (i.e., limitations regarding first linker and portion of the MHC I α chain), have been fully considered and are persuasive. The 35 U.S.C 112(b) rejection of claim 15 is moot.
6. Applicants’ arguments, see Remarks, filed 05/28/2026, with respect to the 35 U.S.C 112(a) rejection (i.e., written description ), have been fully considered and are persuasive. The 35 U.S.C 112(a) rejection of claims 1-2, 9-10, 12-15, 18-21 has been withdrawn.
7. Applicants’ arguments, see Remarks, filed 05/28/2026, with respect to the 35 U.S.C 102(a)(1) rejection, have been fully considered and are persuasive. The 35 U.S.C 102(a)(1) rejection of claims 1-2, and 9 has been withdrawn.
8. Applicants’ arguments, see Remarks, filed 05/28/2026, with respect to the 35 U.S.C 102(a)(1) rejection, have been fully considered and are persuasive. The 35 U.S.C 102(a)(1) rejection of claims 1-2, 9-10, 12-15 and 18-20 has been withdrawn.
9. Applicants’ arguments, see Remarks, filed 05/28/2026, with respect to the 35 U.S.C 103 rejection, have been fully considered and are persuasive. The 35 U.S.C 103 rejection of claims 1 and 3-4 has been withdrawn.
10. Applicants’ arguments, see Remarks, filed 05/28/2026, with respect to the 35 U.S.C 103 rejection, have been fully considered and are persuasive. The 35 U.S.C 103 rejection of claims 1 and 21-24 has been withdrawn.
New Rejections Necessitated by Amendment
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.
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.
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness
(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
1. Claims 1, 12 and 18-24 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/195310 A1 International Pub. Date: Oct. 10, 2019 (here in after “Bethune”) in view of Chen et al., J Exp Med (2005) 201 (8): 1243–1255. (herein after “Chen”); US2015/0344586 Pub. Date: Dec. 3, 2015 (herein after “Georges”); and US2018/0037898 A1 Pub. Date: Feb. 8, 2018 (herein after “Ring”).
Regarding claim 1, Bethune teaches antigenic peptide-MHC molecules, termed comPACTs (see Abstract). In particular, Bethune’s Fig. 1 depicts the design of an exemplary comPACT mini-gene, where SS refers to the optional signal sequence; US1 refers to the first universal target site; neoantigen refers to the antigenic peptide sequence site; US2 refers to the second universal target site; L1 refers to the optional first linker sequence; ß2M refers to the ß-2-microglobulin domain sequence; L2 refers to the optional second linker sequence; MHC heavy chain refers to the MHC heavy chain allele (see pg. 16, para[0066] and Fig. 1). Bethune also teaches that the comPACTs refers to a single polypeptide fusion Including a MHC class I heavy chain comprising, e.g., the α1, α2, and α3 domains that forms an MHC display moiety (see pg. 21, para[00112]). Furthermore, Bethune’s Example 1 teaches that the MHC allele may also be modified or mutated (e.g., Y84A or Y84C) to improve folding or increase binding of the antigenic peptide with MHC protein (see pg. 45, para[00190]). Bethune’s methods and compositions enable rapid identification of antigens targeted by an immune response and isolation of the T cells and thus the T cell receptor (TCR) sequences mediating that response (see pg. 3, para[0006]). Bethune adds that the identification and characterization of antigen-specific T cells may also be applied in the diagnosis, monitoring and prognosis of immune responses and disease in the context of (pre- and post-) therapeutic treatment (see pg. 3, para[0006]).
As such Bethune’s teachings read on the instantly claimed SCT polypeptide, wherein the ß-2-microglobulin domain sequence corresponds to at least a portion of a ß2-microglobulin domain as recited in instant claim 1, the L2 second linker sequence corresponds to the instantly claimed second linker, and the MHC heavy chain corresponds to the instantly claimed functional portion of a MHC I α chain wherein the chain comprises an amino acid substitution compared to a wild-type MHC I α chain, wherein the substitution is of tyrosine for cystine at position 84 relative to the wild-type MHC I α chain, as recited in instant claim 1.
However Bethune does not expressly teach an NY-ESO-1 target peptide, nor wherein the first linker has an amino acid sequence that is GCGGSGGGGSGGGGS (SEQ ID NO: 1).
With respect to an NY-ESO-1 target peptide:
Chen is in the field of structural and kinetic basis for heightened immunogenicity of T cell vaccines (see pg. 1243, Title). Chen teaches that that NY-ESO-1 is one of the most promising tumor-specific antigens, and is expressed by a broad range of tumor types (see pg.1244, right column, second paragraph). Chen adds that natural tumor antigens elicit relatively weak T cell responses and one approach to solve the challenge is to optimize the MHC class I anchor residues in tumor epitopes to enhance binding of the peptide to the MHC class I molecule (see pg. 1243, left column, paragraph 1). Thereby, as best understood, Chen teaches the analogue peptide of wild-type NY-ESO-1157-165 (i.e., SLLMWITQC), with enhanced binding affinity to major histocompatibility class (MHC) I molecules used to elicit stronger T cell responses in cancer patients. Chen achieved this, by correlating the functional, thermodynamic, and structural parameters of TCR-peptide-MHC binding and demonstrated the effect of anchor residue modifications of the human histocompatibility leukocyte antigens (HLA)–A2 tumor epitope NY–ESO-1157–165–SLLMWITQC on T cell receptor (TCR) recognition (see pg. 1243, abstract). The crystal structure of the wild-type peptide (i.e., SLLMWITQC) complexed with a specific TCR shows that TCR binding centers on two prominent, sequential, peptide sidechains, methionine–tryptophan (see pg. 1243, abstract). Cysteine-to-valine substitution at peptide position 9 (i.e., SLLMWITQC), while optimizing peptide binding to the MHC, repositions the peptide main chain and generates subtly enhanced interactions between the analogue peptide (i.e., SLLMWITQV) and the TCR (see pg. 1243, abstract). Binding analyses confirm tighter binding of the analogue peptide to HLA–A2 and improved soluble TCR binding (see pg. 1243, abstract). Recognition of analogue peptide stimulates faster polarization of lytic granules to the immunological synapse, reduces dependence on CD8 binding, and induces greater numbers of cross-reactive cytotoxic T lymphocyte to SLLMWITQC (see pg. 1243, abstract).
With respect to the first linker being a peptide and wherein the first linker has an amino acid sequence that is GCGGSGGGGSGGGGS (SEQ ID NO: 1):
Georges teaches a disulfide-linked multivalent multi-function protein comprising an antibody fragment and one, two or more disulfide-linked MHC class I components (see pg. 1, para[0003]).
Georges adds that the virus-derived peptide is fused to the ß-2 microglobulin via a first linker peptide (see pg. 4, para[0089]); and that in one embodiment the first linker peptide has the amino acid sequence of SEQ ID NO: 139 (see pg. 5, para[0115]). Georges’ SEQ ID NO: 139 consists of GCGGSGGGGSGGGGS (see pg. 5, para[00940]). Additionally, George’s SEQ ID NO: 139 is 100% identical to instant SEQ ID NO: 1.
Furthermore, Georges teaches that the linker has the function to ensure that polypeptides conjugated to each other can perform their biological activity by allowing the polypeptides to fold correctly and to be presented properly (see pg. 19, para[0451]). The peptide linker is rich in glycine, glutamine, and/or serine residues; and these residues are arranged e.g. in small repetitive units of up to five amino acids(see pg. 19, para[0451]). Additionally disulfide-linked multivalent multi-function proteins as reported by Georges, comprising one antigen presenting domain can be produced with improved yields and have an improve thermal stability (see pg. 20, para[0464]). Further without being bound by this theory disulfide-linked multivalent multifunction proteins comprising one antigen presenting domain are more specific with respect to T-cell activation (see pg. 20, para[0464]).
From the teachings of the references, the Examiner recognizes that it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to substitute Bethune’s SS (i.e., optional signal sequence), US1 (i.e., first universal target site) and neoantigen (i.e., antigenic peptide sequence site) and US2/L1 (i.e., second universal target site/optional first linker sequence), with Chen’s NY-ESO-1 and Georges’ SEQ ID NO: 139 in order to arrive at the instantly claimed SCT polypeptide. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because it was known that NY-ESO-1 is one of the most promising tumor-specific antigens, and is expressed by a broad range of tumor types as taught by Chen. And because it was also known that the GCGGSGGGGSGGGGS linker has the function to ensure that polypeptides conjugated to each other can perform their biological activity by allowing the polypeptides to fold correctly and to be presented properly as taught by Georges.
One of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success in performing the suggested substitution given that Bethune’s design of the comPACT mini-gene includes enables rapid identification of antigens targeted by an immune response as well as isolation of the T cells and the TCR sequences mediating that response, which contribute to the diagnosis, monitoring and prognosis of immune responses and diseases in the context of therapeutic treatment. Furthermore, an ordinary skilled artisan would have been motivated to make the substitutions given that optimization of the MHC class I anchor residues in tumor epitopes to enhance binding of NY-ESO-1 (i.e., a target peptide) to the MHC class I molecule was a known approach to strengthen T cell responses elicited by natural tumor antigens, thereby eliciting stronger T cell responses in cancer patients. Finally, an ordinary skilled artisan would also have been motivated with reasonable expectation of success given that disulfide-linked multivalent multi-function proteins comprising one antigen presenting domain can be produced with improved yields and have an improve thermal stability and are more specific with respect to T-cell activation as taught by Georges.
Accordingly, substituting Bethune’s SS (i.e., optional signal sequence), US1 (i.e., first universal target site) and neoantigen (i.e., antigenic peptide sequence site) and US2/L1 (i.e., second universal target site/optional first linker sequence), with Chen’s NY-ESO-1 and Georges’ SEQ ID NO: 139 would support antigenic peptide-MHC molecules (i.e., comPACTs) by constituting a simple substitution of one known element for another to obtain predictable results; and/or use of known technique to improve similar devices (methods, or products) in the same way; and/or some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention, pursuant to KSR.
Regarding claim 12, Georges’ first linker i.e., SEQ ID NO: 139, consists of GCGGSGGGGSGGGGS (see pg. 5, para[00940]). Thereby constituting wherein the second amino acid counted from the N-terminus of the first linker is C, as recited in instant claim 12.
Regarding claim 18, Bethune’s comPACT construct shows wherein after the MHC heavy chain, there is a third linker (see Fig. 1), followed by a purification cluster (i.e., a tag) and a BGH polyA sequence (see Fig. 6).
Regarding claims 19-20, Bethune teaches Table 3, which lists exemplary signal sequences (see pg. 27). Additionally, Bethune discloses that that the signal sequence can be a secretion signal sequence and that secretion signal sequences direct translated proteins in mammalian cells through the secretory pathway, and ensure that the translated proteins are subject to cellular quality control (see pg. 27. para[00130]). Since the term “leader sequence” is used interchangeably with the term “signal sequence”, as described in the instant specification at pg. 22, lines 14-16. Then, Bethune’s teachings read on wherein the claimed single chain trimer (SCT) further comprises a leader peptide, as recited in instant claim 19; as well as, wherein the leader peptide directs the SCT polypeptide to the ER, and facilitates aspects of late secretory processing, as recited in instant claim 20.
Regarding claims 21-23, Bethune teaches that the comPACT polynucleotide and polypeptide may comprise a signal sequence, e.g., encoding a signal peptide in the case of a polynucleotide (see pg. 27, para[00130]). The signal sequence can be a secretion signal sequence; secretion signal sequences direct translated proteins in mammalian cells through the secretory pathway, and ensure that the translated proteins are subject to cellular quality control (see pg. 27, para[00130]). Inclusion of secretory signals can ensure that the comPACT proteins are secreted into the cellular media, such that they are homogenously well-folded and more easily isolated from the media or clarified supernatant (see pg. 27, para[00130]).
However, Bethune does not expressly teach wherein the leader peptide shares 95% or greater sequence identity with a sequence of SUC2 (SEQ ID NO: 19) (i.e., Applicants’ elected species).
Ring teaches methods and compositions for displaying a protein of interest (POI) on the surface of a eukaryotic cell by fusing the POI to a signal polypeptide, a stalk polypeptide, and a surface anchor polypeptide to generate a surface accessible fusion protein (see Abstract). Ring teaches that if a surface accessible fusion protein will be expressed in a yeast cell, the signal polypeptide can be from a yeast protein (e.g., in some cases from the same species of yeast) (see pg. 5, para[0041]). Ring’s examples of suitable signal polypeptides include but are not limited to those from (or derived from) the following yeast proteins: mating factor alpha, Aga2p, Pho5p, and Suc2p (see pg. 5, para[0041]). Furthermore, Ring teaches MLLQAFLFLLAGFAAKISAS as SEQ ID NO: 15 which represents signal polypeptide from SUC2p; which is 100% identical to instant SEQ ID NO: 19.
Regarding claim 24, Ring teaches that expression of proteins on the surface of eukaryotic cells (e.g., yeast cells), a technique known as surface display, can be used for a diverse array of purposes (see pg. 1, para[0002]). For example, because yeast are eukaryotic, using yeast for surface display is well suited for engineering and modifying mammalian proteins (e.g., via directed evolution) that require posttranslational modifications for efficient folding and activity (e.g., cell-surface and secreted proteins such as antibodies, receptors, cytokines, and the like) (see pg. 1, para[0002]). In one example of surface display, a protein of interest is fused to the Aga2p protein, which is naturally used by yeast to mediate cell-cell contacts during mating (see pg. 1, para[0002]).
As such it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to modify the teachings of Bethune, and incorporate the teachings of Ring in order to arrive at the claimed SCT polypeptide wherein the leader peptide shares 95% or greater sequence identity with SEQ ID NO: 19, and wherein the tether peptide is Aga2. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because methods and compositions for displaying a protein of interest (POI) on the surface of a eukaryotic cell by fusing the POI to a signal polypeptide were well-known; and because using yeast for surface display is well suited for engineering and modifying mammalian proteins (e.g., via directed evolution) that require posttranslational modifications for efficient folding and activity (e.g., cell-surface and secreted proteins such as antibodies, receptors, cytokines, and the like). One of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success given that Bethune’s comPACT polypeptide comprises a signal sequence that directs translated proteins in mammalian cells through the secretory pathway and ensure that the translated proteins are subject to cellular quality control. An ordinary skilled artisan would also have been motivated with reasonable expectation of success given that Rings’ signal polypeptides include but are not limited to those from (or derived from) the following yeast proteins: mating factor alpha, Aga2p, Pho5p, and Suc2p; and given that Ring’s Suc2p (i.e., SEQ ID NO: 15) is 100% identical to instant SEQ ID NO: 19. Therefore, Ring’s signal peptides (i.e., SEQ ID NO: 15 and Aga2p) would support the antigenic peptide-MHC molecules (i.e., comPACTs) by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention, pursuant to KSR.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the above claims would have been obvious to one of ordinary skill in the art within the meaning of 35 US..C 103. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references discussed above.
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.
2. Claims 1, 12, 18-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 9, 13, 19-22 and 25 of copending Application No. 18/685,109 in view of Chen et al., J Exp Med (2005) 201 (8): 1243–1255. (herein after “Chen”).
Regarding instant claim 1, copending application No. 18/685,109 claims:
A single chain trimer (S CT) polypeptide comprising or consisting essentially of a target peptide, a first linker, at least a portion of a beta-2 microglobulin domain, a second linker, and at least a portion of a human leukocyte antigen allele B*35 (HLA-B*35) alpha chain; or a pharmaceutically acceptable derivative thereof (see ‘109, claim 1).
The SCT polypeptide of claim 1, wherein the first linker is a peptide (see ‘109, claim 2).
The SCT polypeptide of claim 1, wherein the first linker has an amino acid sequence that is at least about 90% homologous to GCGGSGGGGSGGGGS (SEQ ID NO: 1) (see ‘109, claim 3).
The SCT polypeptide of claim 1, wherein the at least a portion of the HLA-B*35 alpha chain comprises one or more amino acid substitutions compared to a wild-type HLA-B*35 alpha chain (see ‘109, claim 9).
Regarding instant claim 12, copending application No. 18/685,109 claims:
The SCT polypeptide of claim 9, wherein the second amino acid counted from the N-terminus of the first linker is C (see ‘109, claim 13).
Regarding instant claim 18, copending application No. 18/685,109 claims:
The SCT polypeptide of claim 1, further comprising a tag, a third linker, and/or a tether peptide (see ‘109, claim 19).
Regarding instant claim 19, copending application No. 18/685,109 claims:
The SCT polypeptide of claim 19, further comprising a leader peptide (see ‘109, claim 20).
Regarding instant claim 20, copending application No. 18/685,109 claims:
The SCT polypeptide of claim 20, wherein the leader peptide directs the SCT polypeptide to the ER, facilitates ER to Golgi transport, and/or facilitates aspects of late secretory processing (see ‘109, claim 21).
Regarding instant claims 21-23, copending application No. 18/685,109 claims:
The SCT polypeptide of claim 21, wherein the leader peptide shares 95% or greater sequence identity with a sequence of SUC2 (SEQ ID NO: 19) (see ‘109, claim 22).
Regarding instant claim 24, copending application No. 18/685,109 claims:
The SCT polypeptide of claim 19, wherein the tether peptide is Aga2 (see ‘109, claim 25).
One of ordinary skill in the art would have been motivated with reasonable expectation of success to arrive at the claimed SCT by combining claims 1-3, 9, 13, 19-22 and 25 from copending Application No. 18/685,109 with Chen’s NY-ESO-1. Since it was known that Chen’s analogue peptide of wild-type NY-ESO-1157-165 (i.e., SLLMWITQC) enhances the binding affinity to major histocompatibility class (MHC) I molecules used to elicit stronger T cell responses in cancer patients.
Although the claims at issue are not identical, they are not patentably distinct from each. This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicants' arguments filed 05/28/2026, have been fully considered but they are not persuasive.
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).
In this case, articulated reasoning demonstrating that one of ordinary skill in the art would have been motivated to combine the cited prior art has been established. However, the reasoning will be reiterated herewith.
The inventive concept was known prior to the effective filing date of the instant invention.
Bethune teaches a single polypeptide fusion Including a MHC class I heavy chain comprising,
e.g., the α1, α2, and α3 domains that forms an MHC display moiety (i.e., single chain trimer) which also comprises a target peptide, a first linker and a portion of the ß2 microglobulin domain; in addition to comprising the amino acid substitution Y84C at the MHC I α chain (see Bethune’s Fig. 1).
Chen teaches optimization of the MHC class I anchor residues in tumor epitopes to enhance binding of NY-ESO-1 (i.e., a target peptide) to the MHC class I molecule was a known approach to strengthen T cell responses elicited by natural tumor antigens, thereby eliciting stronger T cell responses in cancer patients (see Chen, entire document). Chen also teaches that is one of the most promising tumor-specific antigens, and is expressed by a broad range of tumor types.
Georges teaches a disulfide-linked multivalent multi-function protein comprising an antibody fragment and one, two or more disulfide-linked MHC class I components, wherein the first linker is 100% identical to instant SEQ ID NO: 1. Georges’ invention also comprises ß-2 microglobulin linked via a first linker peptide (see Georges, pg. 5, para[0115], and pg. 4, para[0089]).
Ring teaches expression of proteins on the surface of eukaryotic cells (e.g., yeast cells), a technique known as surface display, can be used for a diverse array of purposes (see pg. 1, para[0002]). Additionally, Ring teaches MLLQAFLFLLAGFAAKISAS as SEQ ID NO: 15 which represents signal polypeptide from SUC2p; which is 100% identical to instant SEQ ID NO: 19. Therefore, since yeast are eukaryotes, using yeast for surface display is well suited for engineering and modifying mammalian proteins (e.g., via directed evolution) that require posttranslational modifications for efficient folding and activity (e.g., cell-surface and secreted proteins such as antibodies, receptors, cytokines, and the like) (see Ring, pg. 1, para[0002]).
Thus, an ordinary skilled artisan would have been motivated by the reasons stated above, and would have had reasonable expectation of success in achieving the suggested substitution, because the cited prior art provides sufficient detail to enable an ordinary skill in the art to carry out the claimed invention. Therefore, contrary to Applicants’ argument, an ordinary skilled artisan would have been motivated to combine Bethune’s, Chen’s Georges’ and Ring’s teachings to achieve the instantly claimed SCT.
With respect to Applicants’ request that the NSDP over claims 1-3, 9, 13, 19, 20-22 and 25 of copending application No. 18/685,109 be held in abeyance until allowable claims are identified, is acknowledged. Accordingly, the double-patenting rejection is maintained.
Conclusion
No claims are allowed.
Applicants’ 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.
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/CLAUDIA ESPINOSA/Patent Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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