CTNF 18/268,125 CTNF 98494 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. Election/Restrictions 08-43 Claims 1, 3-4, 6 and 8-9 are directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 11, 13-14, 16-17, 19, 21-24, 26 and 29-31 are directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104. Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on 02/03/2026 is hereby withdrawn . In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler , 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01. Priority The present application claims status as a 371 (National Stage) of PCT/US2021/064316 filed 12/20/2021, and claims the benefit under 35 U.S.C 119 (e) to U.S. Provisional Application No. 63/128,239 filed 12/21/2020. 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. Claim Status Claims 1-31 were originally filed and amended on 06/16/2023. The amendment cancelled claims 2, 5, 7, 10, 12, 15, 18, 20, 25, 27-28; and amended claims 4, 8-9, 11, 16-17, 19, 24, 26 and 29. Claim/Sequence Interpretation For claims 1, 3, 13, 21 and 30-31, the scope of the amino acid sequence is being interpreted as requiring 100% identity and the same length to at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3 and 4 with any N-/C- terminal additions. For purposes of applying prior art, the claim scope has been interpreted as set forth below per guidance set forth at MPEP 2111. If applicants dispute any interpretation set forth below, Applicants are 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 claims 19 and 29, regarding the scope of “preventing”, it is noted that the instant specification does not define what constitutes “preventing”. Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention. The Merriam-Webster Dictionary defines “preventing” as to keep from happening or existing (see Merriam-Webster, “Preventing” available online at https://www.merriam-webster.com/dictionary/preventing, accessed on 06/10/2026). As such, the Examiner is interpreting the scope of “preventing” as encompassing 100% prevention of growth of a tumor infiltrated with a TAM. Information Disclosure Statement The IDS filed on 06/16/2023 has been considered by the Examiner. Drawings 06-22 AIA The drawings are objected to because there is a lack of distinction between the results depicted based on the choice of color used to represent the different results. For instance Fig. 4, depicts results for a CSSTRESAC-phage and an insertless phage; however, the results cannot be appropriately interpreted because both bars are the same shade of grey . Corrected drawing sheets in compliance with 37 CFR 1.121(d) 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. Nucleotide and/or Amino Acid Sequence Disclosures REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES Items 1) and 2) provide general guidance related to requirements for sequence disclosures. 37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted: In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying: the name of the ASCII text file; ii) the date of creation; and iii) the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying: the name of the ASCII text file; the date of creation; and the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended). When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical. Specific deficiencies and the required response to this Office Action are as follows: Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Required response – Applicant must provide: A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of: A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); A copy of the amended specification without markings (clean version); and A statement that the substitute specification contains no new matter. Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Required response – Applicant must provide: Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers; AND/OR A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of: A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); A copy of the amended specification without markings (clean version); and A statement that the substitute specification contains no new matter. Claim Rejections - 35 USC § 112 07-30-01 AIA 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 the first paragraph of pre-AIA 35 U.S.C. 112: 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 of carrying out his invention. Claims 19, 21-24, 26 and 29-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for treating and killing growth of a tumor infiltrated with a tumor associated macrophage, does not reasonably provide enablement for preventing growth of a tumor. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected to make and/or use the invention. Specifically, the method claims are drawn to preventing growth of a tumor in a subject by administering to the subject a solid particle, wherein the TAM targeting peptide of claim 1 (i.e., TAM comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, and 4), is attached to or displayed on the surface of the solid particle. To address whether sufficient evidence supports the determination that the disclosure does not satisfy the enablement requirement and whether undue experimentation might be needed, the below factors are considered: In re Wands , 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The breadth of the claims: The claims encompass where preventing includes 100% prevention of growth of a tumor infiltrated with TAM. Additionally, the breadth of the claim exacerbates the complex nature of the subject matter to which the present claim is directed, because of the vast number of possible tumor types claimed. The nature of the invention: The invention pertains to using a short TAM-targeting peptide, especially SEQ ID NOs: 1-4, which are free of the art, and direct a solid particle comprising a therapeutic agent and or therapeutic gene to the tumor associated macrophage. The state of the prior art: The art teaches the inventive concept of binding molecules to tumor associated macrophages and method of use; for instance, see WO2020/033663 A2 international publication date February 13, 2020. The art also teaches design, construction, and generation of targeted AAVP particles and method of use, for instance see US 8,470,528 B2 Date of patent: Jun. 25, 2013. However, the art is silent about a TAM comprising at least one amino acid sequence selected from the group consisting of instant SEQ ID NOs: 1-4, because the instant sequences are novel and non-obvious (i.e., free of the art). The level of one of ordinary skill: Practitioners in this art (medical clinicians, pharmacists, doctors and/or pharmaceutical chemists) would presumably be highly skilled in the art for the prevention of tumor growth. The level of predictability in the art: The instant claimed invention is highly unpredictable. If one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains (i.e., preventing growth of a tumor infiltrated with a TAM peptide of claim 1, in a subject), then there is a lack of predictability in the art. Moreover, it is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. The court has indicated that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. (See In re Fisher , 427 F.2d 833, 166 USPQ 18 (CCPA 1970)). This is because it is not obvious from the disclosure of one species, what other species will work. In the instant case, Applicants do not demonstrate that growth of a tumor infiltrated with a TAM of claim 1, in a subject is prevented. The amount of direction provided by the inventor: The specification does not enable any person skilled in the art to which it pertains to use the invention commensurate in scope with the claims. There is a lack of adequate guidance from the specification with regard to the actual prevention of tumor growth as recited in the claims. Applicants fail to provide the guidance and information required to ascertain whether the claimed administration of a solid particle wherein the TAM of claim 1, is attached to or displayed on the surface of the solid particle prevents the growth of a tumor without resorting to undue experimentation. Applicants' limited disclosure is noted but is not sufficient to justify claiming preventing growth of a tumor, as claimed. The existence of working examples: The specification does not articulate the use of targeting peptides in the prevention of tumor growth. Instead, the working examples pertain to the reduction in size, delay tumor growth, inhibition of tumor growth and reduction of the macrophage population in tumors treated with the targeting peptides (see instant specification, pg. 50). However the working examples lack evidence of 100% prevention of growth of a tumor. The quantity of experimentation needed to make or use the invention based on the content of the disclosure: Due to the breadth of the claim, preventing growth of a tumor in a subject by administering the claimed TAM target peptide of claim 1 attached to or displayed on the surface of a solid particle, wherein the solid particles is AAVP would require substantive experimentation, given the claimed targeting peptides are free of the art. After applying the Wands factors and analysis to claims 19,21-24,26 and 29-31, in view of the applicant' s entire disclosure, and considering the In re Wright , In re Fisher and Genentech decisions discussed above, it is concluded that the practice of the invention as claimed in claims 19,21-24,26 and 29-31 would not be enabled by the written disclosure for a method of preventing growth of a tumor infiltrated with a TAM of claim 1, in a subject. Therefore, claims 19,21-24,26 and 29-31 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to prevent growth of a tumor. Applicants can overcome the instant rejection by amending independent claims 19 and 29 to recite “delaying or inhibiting growth of a tumor” instead of preventing growth of a tumor. Claim Rejections - 35 USC § 103 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, 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. 07-23-aia AIA 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. 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 29 is rejected under 35 U.S.C. 103 as being unpatentable over WO2020033663A2 International Publication Date: Feb. 13, 2020 (cited in the IDS filed on 06/16/2023) (here in after “Pang”) . Regarding claim 29, Pang is in the field of binding molecules to tumor associated macrophages and method of use (see Front pg., Title). In particular, Pang teaches a pharmaceutical composition comprising a tumor associated macrophage (TAM) binding molecule (see pg. 21, claim 1), wherein the TAM binding molecule is a peptide (see pg. 21, claim 10), and wherein the peptide comprises a) CRVLRSGSC, or b) CRVLRSGSC with at least one conservative amino acid substitution (see pg. 21, claim 12); and wherein the composition further comprises a delivery agent (see pg. 22, claim 21), and the delivery agent comprises, liposomes, microspheres, nanoparticles, microemulsions, microcapsules, polymer matrices, hydrogels, or viral vectors (see pg. 22, claim 22). Pang also teaches other aspects of the invention, which encompass a method of treating cancer, wherein the method includes administering to a subject a pharmaceutical composition comprising a TAM binding molecule (see pg. 1, para[0005]); and wherein the TAM binding molecule inhibits tumor growth (see pg. 2, para[0006]). Furthermore, Pang teaches that the peptide CRV (CRVLRSGSC) is a cyclic macrophage-targeting peptide and that the CRV selectively homes to tumors and binds with TAMs within said tumors, and that CRV only recognizes TAMs, but not macrophages in atherosclerotic plaques (see pg. 7, para[0027]). As such, an ordinary skilled artisan would have been motivated with reasonable expectation of success before the filing date of the claimed invention to follow the teachings of Pang in order to arrive at the claimed method. One of ordinary skill would have been motivated to do so because it was known that tumor associated macrophage peptides such as CRVLRSGSC bind and inhibit tumor growth. One of ordinary skill would have had a reasonable expectation of success, given that TAM binding molecules such as CRVLRSGSC do not bind to macrophages in atherosclerotic plaques, and given that TAMs were included in pharmaceutical composition that further comprise a delivery agent. Therefore, Pang’s teachings support the instantly claimed method of treating, killing or preventing growth of a tumor infiltrated with a tumor associated macrophage in a subject 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; and/or applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; pursuant to KSR. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention. Examiner’s note: Applicants can overcome the instant rejection by amending independent claim 29 by incorporating the claim limitations as recited in dependent claim 29, and consequently cancelling claim 31. As such, amended claim 29 would read: A method of treating, killing, delaying or inhibiting growth of a tumor infiltrated with a tumor associated macrophage (TAM) in a subject, the method comprising administering to the subject an effective amount of a TAM targeting peptide; wherein the TAM targeting peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1-4 . Conclusion 12-151-07 AIA 07-97 12-51-07 Claim s 1, 3-4, 6, 8-9, 11, 13-14 and 16-17 are allowed. Claims 19, 21-24, 26 and 29-30 are rejected under 35 U.S.C 112(a). Any inquiry concerning this communication or earlier communications from the examiner should be directed to CLAUDIA E ESPINOSA whose telephone number is (703)756-4550. The examiner can normally be reached Monday-Friday 9:30-5:30 EST. 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, LIANKO GARYU can be reached at (571) 270-7367. 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. /CLAUDIA ESPINOSA/ Patent Examiner, Art Unit 1654 /LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654 Application/Control Number: 18/268,125 Page 2 Art Unit: 1654 Application/Control Number: 18/268,125 Page 3 Art Unit: 1654 Application/Control Number: 18/268,125 Page 4 Art Unit: 1654 Application/Control Number: 18/268,125 Page 5 Art Unit: 1654 Application/Control Number: 18/268,125 Page 6 Art Unit: 1654 Application/Control Number: 18/268,125 Page 7 Art Unit: 1654 Application/Control Number: 18/268,125 Page 8 Art Unit: 1654 Application/Control Number: 18/268,125 Page 9 Art Unit: 1654 Application/Control Number: 18/268,125 Page 10 Art Unit: 1654 Application/Control Number: 18/268,125 Page 11 Art Unit: 1654 Application/Control Number: 18/268,125 Page 12 Art Unit: 1654 Application/Control Number: 18/268,125 Page 13 Art Unit: 1654
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