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 .
Applicant’s amendment, filed on 7/29/2024, is acknowledged.
Claims 5, 6, 8, 10-15, 18, 22, 23, 25, 27-29, 31, 34, 35, 37-43, 45, 48, and 49 are cancelled.
Claims 1-4, 7, 9, 16, 17, 19-21, 24, 26, 30, 32, 33, 36, 44, 46, and 47 are currently pending.
Election/Restrictions
Applicants’ election with traverse of Group I, claims 1-4, 7, and 9, directed to genetically modified immune cells overexpressing FAP; and the species of: i) NK92 cells, and ii) CXCL9, filed on 6/18/2026, is acknowledged. The traversal is on the grounds that the cited reference is not relevant to the instantly claimed subject matter. This is not found persuasive because as stated in the Restriction Requirement mailed on 4/20/2026, the cited reference teaches pharmaceutical compositions comprising immune cells genetically modified to overexpress FAP (i.e., the limitations of instant claim 1), and therefore no special technical feature exists for the Groups of Invention.
The requirement is still deemed proper and is therefore made FINAL.
Claim 3 is drawn to an unelected species of invention (T-cells).
Claims 3, 16, 17, 19-21, 24, 26, 30, 32, 33, 36, 44, 46, and 47 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions and/or species.
Claims 1, 2, 4, 7, and 9 are under examination as reading on a pharmaceutical composition comprising genetically modified immune cells overexpressing FAP.
Priority
Applicant’s claim for the benefit of a prior-filed U.S. Provisional App. Nos. 63/142,300 and 63/239,526, filed on January 27, 2021 and September 1, 2021, respectively, is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 7/26/2023 and 12/11/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner in their entireties entirety.
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 1 - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
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 incorporation-by-reference paragraph, 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 2 – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Specifically, the instant specification discloses nucleic acid sequences in ¶[00178], [00289] without the corresponding sequence identifiers.
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.
Specification
The use of the terms:
Matrigel® (¶[00127], [00256], [00259], [00268], [00272], [00305], [00314], [00323], [00327]);
AlexaFluor® (¶[00174], [00256], [00293], [00305], [00307]);
SYTOX™ Blue (¶[00174], [00307]);
GraphPad Prism® (¶[00174], [00227], [00285], [00303], [00307]);
PureLink™ (¶[00178], [00289]);
NanoDrop™ (¶[00178]);
GoTaq® (¶[00178]);
SYBR™ Green (¶[00178], [00289]);
StepOnePlus™ (¶[00178], [00289]);
Pierce™ (¶[00188], [00291], [00295]);
cOmplete™ (¶[00188], [00295]);
Tween® (¶[00233]);
gentleMACS™ (¶[00235]);
LIVE/DEAD™ (¶[00235]); and
Zombie NIR™ (¶[00235]);
which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112
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 1, 2, 4, 7, and 9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventors, at the time the application was filed, had possession of the claimed invention.
Claims 1, 2, 4, 7, and 9 encompass a broad genus of pharmaceutical compositions comprising genetically modified immune cells with the function of “overexpress fibroblast activation protein (FAP)”, which encompasses any genetic modification of the immune cells to lead to this function.
Claim 9 additionally encompasses a broad genus of pharmaceutical compositions comprising genetically modified immune cells that overexpress FAP, and are further modified to have the functions of “express one or more chemokines” and optionally “overexpressed upon engagement with a cancer cell”.
However, the specification fails to provide adequate written description support for a genus of pharmaceutical compositions comprising a broad genus of genetically modified immune cells with no recited structure having the desired functional properties required to practice the claimed function of “overexpress FAP” (claims 1, 2, 4, 7, and 9), or chemokines with the function of “overexpressed upon engagement with a cancer cell” (claim 9).
The claims are not supported by a description that satisfies 35 U.S.C. § 112(a) or 35 U.S.C. § 112, first paragraph. "[T]he test for sufficiency [of the written description] is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Phanns., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane).
A "sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus." Id. at 1350. "[A]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials." Id.
"[F]unctional claim language can meet the written description requirement when the art has established a correlation between structure and function." Id. "But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species." Id.
"A sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
The specification discloses human NK cells express the protein fibroblast activation protein (FAP; ¶[00200]-[00204], Fig. 7B 7C, and 7F). The specification further discloses that inhibition of FAP reduces migration of NK cells (¶[00260]-[00261], Fig. 13), as well as NK cell extravasation and tumor infiltration (¶[00263]-[00265], Fig. 14 and 15).
The specification discloses that some of the genetically modified cells are intended to treat cancer (¶[0008]): “…techniques are disclosed for treating cancer through the administration of genetically modified immune cells that overexpress fibroblast activation protein. In embodiments, the techniques are intended to treat cancer…”
The specification further discloses (¶[00334]): “[t]here are numerous methods by which the immune cells of the present invention may be genetically modified to overexpress fibroblast activation (FAP) protein. One exemplary method is genetic transformation, a process by which the genetic material carried by an individual cell is altered by the incorporation of foreign (exogenous) DNA into its genome. Standard techniques may be used for recombinant DNA, oligonucleotide synthesis, and tissue culture and transformation (e.g., electroporation and lipofection). Enzymatic reactions and purification techniques may be performed according to manufacturer's specifications or as commonly accomplished in the art or as described herein. The foregoing techniques and procedures may be generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification.”
The specification does not disclose any working examples of genetically modified immune cells overexpressing FAP, not any working examples of methods of treating cancer comprising administration of such cells. The specification does not disclose any specific working example of genetically modified cells, or whether the modifications comprise modification that alter FAP expression and how. The specification also does not disclose any examples of genetically modified immune cells to express cytokine structures either with or without the function of “overexpressed upon engagement with a cancer cell”.
With respect to representative number of species, see AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014). Also, see MPEP 2163 Il(A)(3)(a))(ii):
A representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See Abb Vie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.").
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
In the instant case, the specification does not disclose any representative species of genetically modified immune cells overexpressing FAP, which is not representative of the claimed genus of modified cells with this function (claims 1, 2, 4, 7, and 9). Neither does the instant specification disclose any representative species of genetically modified immune cells further modified with the function “express one or more chemokines” and optionally “overexpressed upon engagement with a cancer cell” (claim 9).
Moreover, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed compositions comprising genetically modified immune cells to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). The Court reiterated that adequate written description must “contain enough information about the actual makeup of the claimed products . . . .” The Court simultaneously suggested that the “newly characterized antigen” test “flouts” section 112 because it “allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen.” The Court concluded that for written description of an antibody to be adequate when presented with “functional” terminology, there must be an established correlation in the art between structure and function.
Given the broadly claimed classes of genetically modified cells, and in the absence of sufficient disclosure of relevant identifying characteristics for the broadly claimed classes of genetically modified cells, the patentee must establish “a reasonable structure-function correlation” either within the specification or by reference to the knowledge of one skilled in the art with functional claims. AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014), MPEP 2163.
The instant specification provides no relationship between a cell’s structure and the function of “overexpress FAP” (claims 1, 2, 4, 7, and 9), or further modified with the function “express one or more chemokines” and optionally “overexpressed upon engagement with a cancer cell” (claim 9). The instant specification discloses that this is possible, however does not provide sufficient guidance on how to generate cells with this claim function that would allow one with ordinary skill in the art to envision a reasonable structure-function correlation between a genetically modified cell and the recited functions.
Possession is not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Sufficient description to show possession of such a genus may be achieved by means of a recitation of a representative number of genetically modified cells falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. See Eli Lilly, 119F.3d at 1568, 43 USPQ2d at 1406.
Claims 1, 2, 4, 7, or 9 do not meet the requirements of 35 U.S.C. 112(a) for written description.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Reisfeld et al. (WO2007149518).
Reisfeld et al. teaches DNA compositions comprising FAP epitopes (claim 1), including human FAP (claim 3). Reisfeld et al. further teaches that the DNA encoding the human FAP is expressible in immune cells, and the compositions will deliver the FAP DNA to immune cells allowing them to overexpress FAP (pg. 7): “…attenuated Salmonella carrier includes DNA encoding at least one epitope of FAP, which is expressible in immune cells. The bacteria does not itself express FAP, but rather delivers the FAP DNA to immune cells (e.g., macrophages and dendritic cells), which in turn express FAP. Such compositions can prolong antitumor effects up to 10 months…”
It would have been obvious to one with ordinary skill in the art, to have modified the teaching of Reisfeld et al. to make pharmaceutical compositions comprising the immune cells genetically modified to overexpressing FAP (i.e., the limitations of instant claim 1) with a reasonable expectation of success, as Reisfeld et al. provides guidance to one with ordinary skill in the art to make such compositions, for example with an attenuated Salmonella carrier. One would have been motivated to make this change for the purposes of making pharmaceutical compositions comprising immune cells genetically modified to overexpress FAP to use to prolong antitumor effects of an anti-FAP tumor immune response for up to 10 months.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEC JON PETERS whose telephone number is (703)756-5794. The examiner can normally be reached Monday-Friday 8:30am - 6:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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