CTNF 18/323,672 CTNF 90072 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Restriction//Election Applicant’s election of Group I (Claims 1-3, 9 and 16-23), as well as Applicant’s election of Species 1A (SEQ ID NO.: 1 (Claims 1-3, 24-26, 33 and 34)), Species 2A (RAF/MEK/ERK (Claims 1, 16 and 17)), and Species 3A (C-RAF, ERK or MAPK (Claims 1, 16 and 17)), in the reply filed on 29 September 2025, are acknowledged. Because Applicant did not distinctly and specifically point out whether the election is being made with or without traverse nor 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). Claims 24-34 and 38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected Groups II and III , there being no allowable generic or linking claim. In addition, Claims 2, 3, 18-20 and 23 are withdrawn as being drawn to nonelected species; therefore, all limitations relating to said nonelected species are also withdrawn from further consideration at this time. The election is being treated as an election without traverse. Applicant timely responded to the restriction (election) requirement mailed on 31 July 2025 in the reply filed on 29 September 2025. In addition, the Examiner requested in a telephonic correspondence held on 27 October 2025 that Applicant elect a subspecies of SEQ ID NO.: 1 which represents a protein/peptide such that each of the wild card positions (indicated by an "X") is assigned a definitive amino acid. See the attached Examiner Initiated Interview summary (.pdf). Applicant elected SEQ ID NO.: 2 as a subspecies of SEQ ID NO.: 1. 12-151 AIA 26-51 12-51 Status of Claims Claims 2-3, 18-20, 23-34 and 38 show incorrect status identifiers. Applicant is reminded that claims 2-3, 18-20, 23-34 and 38 should be labeled: “(Withdrawn)”; remaining claims should be identified appropriately (MPEP 714 (II)(C)(A)) (See 37 CFR 1.121 (c)). Appropriate correction is required. Applicant is required to provide a new claim set showing correct status identifiers in the response to this Office Action. Claims 1-3, 9, 16-34 and 38 are pending. Claims 1, 9, 16-17 and 21-22 are rejected. Claims 1 and 9 are objected to. Priority Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. §119(e) or under 35 U.S.C. §120, §121, or §365(c) is acknowledged. This application claims benefit of provisional application 63/345,591, filed on 05/25/2022. Applicant has complied with all of the conditions for receiving the benefit of an earlier filing date under 35 U.S.C. §120 or §365(c). However, the subject matter of claim 9 which describes a specific PAN domain sequence as represented by SEQ ID NO.: 2 is not supported by the provisional application. Therefore, claim 9 has the effective filing date of the filing date of the instant application which is 25 May 2023. Claims 1, 16-17 and 21-22 have the effective filing date of 25 May 2022. Information Disclosure Statement The information disclosure statements (IDS) submitted on 12 October 2023 (referred to as 12 October 2023-A, 12 October 2023-B, 12 October 2023-C, and 12 October 2023-D) are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the Examiner. Oath or Declaration It is noted that an oath or declaration has not been filed with this application. MPEP 602.01 (a)(I) states, in part: “The inventor, or each individual who is a joint inventor of a claimed invention, in an application for patent (other than a provisional application) must execute an oath or declaration directed to the application, except as provided for in 37 CFR 1.64. An oath or declaration must: (1) identify the inventor or joint inventor executing the oath or declaration by their legal name; (2) identify the application to which it is directed; (3) include a statement the person executing the oath or declaration believes the named inventor or joint inventors to be the original inventor or an original joint inventor of a claimed invention in the application for which the oath or declaration is being submitted; and (4) state that the application was made or authorized to be made by the person executing the oath or declaration. Items (3) and (4) above are requirements of 35 U.S.C. 115(a) and (b).” Submission of such an oath or declaration must be filed in order for examination of the application to proceed. Forms PTO/AIA/01 through PTO/AIA/11 may be used when submitting the inventor’s oath or declaration in an application filed on or after September 16, 2012 (MPEP 602.01 (a)(IV)). Sequence Listing Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures 37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted: 1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying: a. the name of the XML file b. the date of creation; and c. the size of the XML file in bytes; or 2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying: a. the name of the XML file; b. the date of creation; and c. the size of the XML file in bytes. SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS: Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because the “Sequence Listing XML,” as a separate part of the disclosure, is defective, damaged or unreadable. Refer to document “Sequence Listing in Computer Readable Format is Defective” dated 30 November 2025. Required response - Applicant must provide: • A replacement “Sequence Listing XML” part of the disclosure, as described above submitted in accordance with either item 1. or 2.; together with o A statement that identifies the location of all additions, deletions or replacements of sequence information relative to the replaced “Sequence Listing XML” as required by 37 CFR 1.835(b)(3); o A statement that indicates support for the replacement “Sequence Listing XML” in the application, as filed, as required by 37 CFR 1.835(b)(4); and o A statement that the replacement “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(b)(5). AND • A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125, inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of: o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); o A copy of the amended specification without markings (clean version); and o A statement that the substitute specification contains no new matter. See MPEP 2416. Drawings It is noted that Applicant filed a petition to accept color drawings on 27 October 2023. The petition was GRANTED on 19 December 2023. 06-37 AIA The drawings were received on 25 May 2023 . These drawings are objected to . (1) Figures 6A and 6B are objected to as failing to comply with 37 CFR 1.84(l) and (p)(3). 37 CFR 1.84(l) recites: All drawings must be made by a process which will give them satisfactory reproduction characteristics. 37 CFR 1.84(p)(3) recites: Numbers, letters, and reference characters must measure at least 0.32cm (1/8 inch) in height. Figures 6A and 6B show amino acid sequences that are unreadable. Therefore, it is not clear if any of those sequences represent the amino acid sequence of claimed SEQ ID NO.: 1. (2) Figure 8A is objected to for not meeting MPEP 608.02 (V) Drawing standards 37 CFR 1.84 (u) Numbering of views. (1) The different views must be numbered in consecutive Arabic numerals, starting with 1, independent of the numbering of the sheets and, if possible, in the order in which they appear on the drawing sheet(s). Partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. View numbers must be preceded by the abbreviation "FIG." Where only a single view is used in an application to illustrate the claimed invention, it must not be numbered and the abbreviation "FIG." must not appear. (2) Numbers and letters identifying the views must be simple and clear and must not be used in association with brackets, circles, or inverted commas. The view numbers must be larger than the numbers used for reference characters. Figure 8A is designated as a 'continued' figure as "FIG. 8A (Continued)". To resolve this minor informality Figure 8A can be amended to read "FIG. 8A" and "FIG. 8B". Other parts of the figure (FIG. 8C and FIG. 8D) should be similarly re-labeled . 06-22 Corrected drawing sheets in compliance with 37 CFR 1.121(d) ( and/or appropriate amendment to the specification ) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance. Claim Objections 07-29-01 AIA Claim s 1 and 9 are objected to because of the following informalities: (1) Claim 1 recites the acronym "PAN", the first recitation of which should be preceded by the full name of the term for which it stands. Claim 1 should read: "...attaching a plasminogen-apple-nematode (PAN) domain..." (See clean copy specification filed on 27 October 2023, pg. 2, cont. para. [0005]). (2) Claim 9 recites: "...at least 90%identical to...", which should read: "...at least 90% identical to..." That is, there should be a space between the percent sign and the word 'identical' . Appropriate correction is required. Claim Rejections - 35 U.S.C. § 103 07-06 AIA 15-10-15 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 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. 07-20-aia AIA 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 of this title, 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. 07-20-02-aia AIA 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. 07-21-aia AIA Claim s 1 and 16-17 are rejected under 35 U.S.C. §103 as being unpatentable over Bowdish et al . (Pub. No. WO 2014/145159 A2) as evidenced by Benaroudj et al . (Nature Cell Biol. 2000, 2: 833-839), in view of Gong et al . (PLoS ONE, 2012, 7(1): 1-10) . [Gong et al . cited on the IDS submitted 12 October 2023-A.] Bowdish et al . as evidenced by Benaroudj et al . addresses some of the limitations of claim 1. Regarding claim 1, pertaining to a method for modulating protein function, the method comprising modifying a target protein by attaching a PAN domain or a functional fragment thereof to the target protein, thereby promoting internalization of the target protein, wherein the target protein does not comprise a native PAN domain, Bowdish et al . shows combining a target binding region that binds a cell surface target at the cell surface and a charged protein moiety (CPM) that promotes internalization into cells in order to provide penetration-enhanced targeted proteins (PETPs). Both the target binding region and the CPM effect penetration (pg. 1, para. 3). In some embodiments, the target binding region comprises a domain selected from a group which includes a PAN domain (pg. 6, para. 3). The target binding region and CPM are the protein core of the PETP. However, this protein entity may comprise additional modules, including cargo regions, intended for delivery into cells. These cargo regions may be proteins, peptides, small molecules, and nucleic acids (pg. 27, last para.). Bowdish et al . does not explicitly show that a PAN domain promotes degradation of the target protein, with regard to claim 1. Benaroudj et al . provides information from which one of ordinary skill in the art would have understood that the fusion protein comprising a PAN domain and a (cargo) target protein, as shown by Bowdish et al ., would have promoted degradation, by way of addressing the limitations of claim 1. Regarding claim 1, Benaroudj et al . teaches that PAN (proteasome-activating nucleotidase) stimulates protein degradation (pg. 833, Abstract). The PAN complex offers many technical advantages for dissecting the mechanisms by which ATPases promote protein degradation by the 20S particle (pg. 833, column 2, para. 1). Six ATPases homologous to PAN, comprise a base that associates with the 20S proteasome particle, whereas the nine others form a ‘lid’ that is necessary for degradation of ubiquitin-conjugated proteins (pg. 833, column 2, para. 1). It seems likely that PAN evolved initially as a molecular chaperone and only later became functionally linked to proteolysis (pg. 838, column 1, para. 2). That is, Benaroudj et al . shows that PAN has ATPase activity which is related to the process of ubiquitination, and, therefore, protein degradation, which employs proteasomes. Gong et al . provides information from which one of ordinary skill in the art would have been motivated to have selected a PAN domain for promoting target protein internalization and degradation, as shown by Bowdish et al . as evidenced by Benaroudj et al ., rather than the PAN protein, as shown by Benaroudj et al ., by way of addressing the limitations of claim 1. Regarding claim 1, Gong et al . shows a host cell-binding protein, P104, produced by Toxoplasma gondii which contains 10 PAN/apple domains. T. gondii is an intracellular parasite that invades nucleated cells, causing toxoplasmosis in humans and animals worldwide (pg. 1, Abstract; and pg. 2, Fig. 1A). Results of the described study suggest that P104, expressed at the apical end of the extracellular parasite, may function as a ligand in the attachment of T. gondii to CS (chondroitin sulfate) or other receptors on the host cell, facilitating invasion by the parasite (pg. 1, Abstract). PAN/apple domain proteins in T. gondii may perform different, but important, functions separately or collaboratively. The described work is crucial for understanding the molecules that are involved in the invasion process, and could lead to the development of drugs or vaccine candidates for T. gondii (pg. 9, column 2, para. 1). That is, Gong et al . shows that individual domains of the PAN protein perform separate or different functions, which would motivate one of ordinary skill in the art to select a PAN domain for a specific fusion construct, depending on the intended use of said construct. In other words, it is not necessary to attach the entire PAN protein to the target protein in order to transfer PAN functionality to the resulting fusion polypeptide. Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have modified the method for modulating protein function, comprising attaching a PAN domain to a target protein in order to promote internalization of said target protein, wherein the target protein does not comprise a native PAN domain, as shown by Bowdish et al . as evidenced by Benaroudj et al ., by conjugating a PAN domain to the target protein so as to promote degradation of said target protein, with a reasonable expectation of success, because Benaroudj et al . shows that the PAN protein has biophysiological characteristics which include ATPase function which is, in turn, involved in the process of ubiquitination and/or protein degradation (MPEP 2143 (I)(G)). Although Benaroudj et al . does not show a PAN domain explicitly, it would have been obvious to one of ordinary skill in the art, in view of Bowdish et al ., to have selected that particular domain of the PAN protein which would have promoted target protein internalization and degradation, since the PAN protein exhibits both properties (MPEP 2143 (I)(G)). One of ordinary skill in the art would have been motivated to have made that modification, because Gong et al . shows that the portion of the PAN protein described as the PAN domain ( i.e ., with conserved cysteine loci) is critical in performing different physiological functions in the cell, including attachment to host cells and internalization; e.g ., invasion of cells by the pathogen-related PAN-containing proteins. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention. Bowdish et al . further addresses some of the limitations of claims 16 and 17. Regarding claims 16 and 17, pertaining to the target protein is involved in the RAF/MEK/ERK signaling cascade, and is selected from C-RAF, ERK, and MAPK, Bowdish et al . shows that, in some embodiments, the cargo region comprises ST5 or a functional fragment thereof. Suppression of tumorigenicity 5 is a protein that in humans is encoded by the ST5 gene. STS protein preferentially binds to the SH3 domain of c-Abl kinase, and acts as a regulator of MAPK1/ERK2 kinase, which may contribute to its ability to reduce the tumorigenic phenotype in cells (pg. 133, para. 3-4 [the MAPK/ERK signaling pathway is a genus of signaling pathways which include RAF/MEK/ERK]). Although Bowdish et al . does not show that the target protein is C-RAF, ERK or MAPK, it would have been obvious to one of ordinary skill in the art to have substituted the ST5 protein with the ERK or MAPK protein as the target protein, because ST5 indirectly regulates/is involved in the MAPK/ERK signaling pathway, and therefore, such a substitution would result in the target protein having the same biophysiological function (MPEP 2143 (I)(B)(3)) . 07-22-aia AIA Claim 9 is rejected under 35 U.S.C. §103 as being unpatentable over Bowdish et al . as evidenced by Benaroudj et al ., in view of Gong et al ., as applied to claim s 1, 16 and 17 above, and further in view of Muchero et al . (Pub. No. US 2021/0072228 A1) as evidenced by NCBI global align/STIC sequence search ((SEQ ID NO: 2) Downloaded on 05 December 2025) . Bowdish et al . as evidenced by Benaroudj et al ., in view of Gong et al ., as applied to claims 1, 16 and 17 above, do not show: 1) the PAN domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 2 [species election]. Muchero et al . shows a method for determining that a candidate protein is an immunoregulatory protein when at least one Plasminogen Apple Nematode (PAN) domain is found in the sequence (pg. 2, para. [0013] [nexus to Bowdish et al .- proteins containing PAN domains]). Another aspect of the described disclosure is directed to a method for screening for a therapeutic compound targeting a PAN domain in a protein (pg. 6, para. [0099]). Regarding claim 9, in some embodiments, the PAN domain-containing protein is Hepatocyte Growth Factor (HGF), or a homolog thereof. In some embodiments, the HGF has an amino acid sequence that is at least 70%, 73% 75%, 78%, 80%, 83%, 85%, 88%, 90%, 93%, 95% or 99%, or more identical to SEQ ID NO: 49 (pg. 8, para. [0137]). Muchero et al . shows that the amino acid sequence of SEQ ID NO.: 49 is presented on pg. 97. Muchero et al . does not explicitly show the relationship between SEQ ID NO.: 49 and instantly-claimed SEQ ID NO.: 2. NCBI global align/STIC sequence search shows that the first 125 amino acids of SEQ ID NO.: 49 is 100% identical to the amino acid sequence of SEQ ID NO.: 2. Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have modified the method for modulating protein function, comprising attaching a PAN domain to a target protein in order to promote internalization of said target protein, wherein the target protein does not comprise a native PAN domain, as shown by Bowdish et al . as evidenced by Benaroudj et al ., and Gong et al ., as applied to claims 1, 16 and 17 above, by attaching a PAN domain that is at least 90% identical to SEQ ID NO.: 2 [species election], with a reasonable expectation of success, because Muchero et al . shows a PAN protein with a domain that is 100% identical to the amino acid sequence of instant SEQ ID NO.: 2 (MPEP 2143 (I)(G)). In addition, Muchero et al . shows that specific PAN domains within the protein may be targeted ( i.e ., recognized as an entity apart from the entire protein) and Gong et al . shows that PAN domains can be considered as individually functioning units, because they can exhibit different functionalities; e.g ., internalization and degradation. Therefore, it would have been obvious to have attached the PAN domain represented by SEQ ID NO.: 2, as shown by Muchero et al ., to a target protein to be internalized and degraded by a cell, with the reasonably predictable expectation that the target protein would have been internalized by said cell and degraded therein (MPEP 2143 (I)(G)). One of ordinary skill in the art would have been motivated to have made that modification, because Gong et al . shows that the portion of the PAN protein described as the PAN domain ( i.e ., with conserved cysteine loci) is critical in performing different physiological functions in the cell, including attachment to host cells and internalization; e.g ., invasion of cells by the pathogen-related PAN-containing proteins. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention . 07-22-aia AIA Claim s 21 and 22 are rejected under 35 U.S.C. §103 as being unpatentable over Bowdish et al . as evidenced by Benaroudj et al ., in view of Gong et al ., as applied to claim s 1, 16 and 17 above, and further in view of Groll et al . (Nature Lett. 2008, 452(10): 755-759) . Regarding claim 21, Gong et al . further shows a host cell-binding protein, P104, produced by Toxoplasma gondii which contains 10 PAN/apple domains. T. gondii is an intracellular parasite that invades nucleated cells, causing toxoplasmosis in humans and animals worldwide (pg. 1, Abstract; and pg. 2, Fig. 1A). That is, Gong et al . shows a target protein ( i.e ., P104) which is associated with a pathogen and which has a PAN domain. Bowdish et al . as evidenced by Benaroudj et al ., in view of Gong et al ., as applied to claims 1, 16 and 17 above, do not show: 1) the target protein is associated with a pathogen (and does not have a PAN domain) [Claim 21]; and 2) the target protein is SylA [Claim 22]. Groll et al . provides information from which one of ordinary skill in the art would have been motivated to have incorporated a target protein associated with a pathogen, such as SylA, into the polypeptide comprising a PAN domain attached to a target protein, as shown by Bowdish et al ., by way of addressing the limitations of claims 21 and 22. Regarding claims 21 and 22, Groll et al . teaches that pathogenic bacteria often use effector molecules to increase virulence. Strains of Pseudomonas syringae pv. syringae (Pss) secrete syringolin A (SylA). Groll et al . shows that SylA is a virulence factor, because a SylA-negative mutant in Pss strain B728a was markedly less virulent on its host, Phaseolus vulgaris (bean). The described study shows that SylA irreversibly inhibits all three catalytic activities of eukaryotic proteasomes, thus adding proteasome inhibition to the repertoire of modes of action of virulence factors (pg. 755, column 1, Abstract [nexus to Benaroudj et al .- involvement of proteasomes in ubiquitination]). Incubation of SK-N-SH (human neuroblastoma) cells with SylA resulted in a dose dependent decrease of proteasome activity. Incubation of SK-N-SH (human neuroblastoma) cells with SylA resulted in a time-dependent accumulation of ubiquitinated proteins (pg. 756, column 1, para. 1). Groll et al . further teaches that there is increasing evidence that the ubiquitin–proteasome degradation pathway is essential for pathogen defense and disease immunity of plants. Pss appears to capitalize on this by inhibiting the host proteasome using SylA, thereby suppressing host defense reactions directly or indirectly. It also remains to be seen whether the proteasome is the sole target of SylA. Previous studies have shown that the host proteasome has been instrumentalized by plant pathogens to suppress host defense reactions by type III effectors mediating proteasomal degradation of specific host proteins (pg. 757, column 1, para. 1). That is, Groll et al . shows that syringolin A (SylA), which is produced by the pathogen P. syringae , affects the proteasome-ubiquitin pathway which is involved in the degradation of proteins; i.e. , like the PAN domain. Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have modified the method for modulating protein function, comprising attaching a PAN domain to a target protein in order to promote internalization and degradation of said target protein, wherein the target protein does not comprise a native PAN domain, as shown by Bowdish et al . as evidenced by Benaroudj et al ., in view of Gong et al ., as applied to claims 1, 16 and 17 above, by incorporating into the method a target protein which is associated with a pathogen, such as SylA [Claims 21 and 22], with a reasonable expectation of success, because Groll et al . shows that syringolin A (SylA), like the PAN domain, affects the proteasome-ubiquitin pathway, which is involved in the degradation of proteins (MPEP 2143 (I)(F,G)). That is, it would have been obvious to one of ordinary skill in the art of modulating protein function to have produced a fusion polypeptide between a PAN domain and a target protein with similar biochemical/biophysical properties so as to boost the desired properties of the polypeptide, such as promotion of internalization and degradation of the target protein (MPEP 2143 (I)(C)). In addition, continuous, repetitive or duplicative parts or steps are claim language scenarios that demonstrate a prima facie case of obviousness (MPEP 2144.04 (V)(E) and (VI)(B)). One of ordinary skill in the art would have been motivated to have made that modification, because Groll et al . teaches that proteasome inhibitors form a promising new therapeutic class of drugs against cancer and other diseases, causing intense interest in such molecules. SylA was recently shown to inhibit proliferation and induce apoptosis in neuroblastoma and ovarian cancer cells (pg. 757, column 2, para. 1). That is, a polypeptide comprising two components which both affect the proteasome ( e.g ., a PAN domain + SylA) would improve the therapeutic effect of Syl A alone in the treatment of various diseases or disorders. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention. Conclusion No claims are allowed. This Office action is a Non-Final action. A shortened statutory period for reply to this action is set to expire THREE MONTHS from the mailing date of this action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHARON M PAPCIAK whose telephone number is (571)272-6235. The examiner can normally be reached M-F 8:30am-5:00pm. 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, Melenie Gordon can be reached at 571-272-8037. 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. /SMP/Examiner, Art Unit 1651 /Michelle F. Paguio Frising/Primary Examiner, Art Unit 1651 Application/Control Number: 18/323,672 Page 2 Art Unit: 1651 Application/Control Number: 18/323,672 Page 3 Art Unit: 1651