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 .
Claim Status
In the reply filed 06 July 2026, Applicant has amended claims 80, 88, 93, 95, 97-98, 103-105, and Claims 1-79, 81-87 are cancelled.
Therefore, 80, and 88-105 are herein pending.
Election/Restrictions
Applicant previously elected without traverse of Group 3: claims 80, and 88-105, which is drawn to a method of modifying an acceptor cell or making a modified cell in the reply filed on 02 February 2026.
Applicant has cancelled non-elected claims 1-79 and 81-86 of Groups1-2 and 4 on 02 February 2026.
Therefore, claims 80, and 87-105 are under current examination.
Priority
This application was filed 12/17/2022 and is a 371 application of PCT/US2021/038087 filed on 06/18/2021, which claims benefit to the Provisional Application 63040860 filed on 06/18/2020. Thus, the earliest possible priority for the instant application is 06/18/2020.
Withdrawn Abstract Objections
Applicant has submitted amended abstract on 06 July 2026, and compliant with MPEP §608.01(b). Therefore, the objection to abstract have been withdrawn.
Maintained Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claim 80, 88, 91, 97 and 98 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tanja et al., (EP2876441B1; Pub. Date: 25 Oct. 2017; cited in IDS filed 06/12/2023; hereinafter “Tanja”). This rejection is maintained for reasons of record and further explained below.
Regarding claims 80, 88, 97 and 98 Tanja discloses a method of modifying acceptor cell comprising contacting said culturing the donor cells and acceptor cells in a culture medium in the presence of a substrate for a first period of time to allow donor and acceptor cells to attach to said substrate [0006], [0012], wherein at least one of the membrane-associated moiety, extracellular moiety, intracellular moiety, or the cargo molecule is exogenous (i.e., viral genome [0107], mRNA, microRNA, DNA, nanoparticles [0031]) to the plurality of donor cells (in one of the examples donor cells were transfected with the transferrin receptor-mCherry (transferrin receptor which are extracellular moiety is exogenously introduced to the donor cell) and in another example donor cells were transfected with proteins (proteins are membrane associated moiety which is exogenously introduced to the donor cell); paragraph [0048], [0080], [0105], Fig. 13B, C). Therefore, POSITA would have been anticipating at the time of the Tanji’s invention the membrane associated moiety presence in different level than donor cell, accordingly, POSITA could anticipate after contact a detectable amount of the membrane-associated agent (at least 1%) increase in the acceptor cells (Figs. 19 A-B).
Furthermore, Tanja discloses the composition comprising a plurality of donor cells, the plurality of donor cells comprising a membrane-associated agent, the agent comprising: a membrane- associated moiety, and one or both of an extracellular moiety or an intracellular moiety (donor cells containing one more traceable substances are provided in the invention wherein traceable substance adhere to the external plasma membrane (traceable substance are the membrane associated extracellular moieties which can be selected from the group consisting of cell vesicles, protein aggregates, mRNA, microRNA, DNA, or nanoparticles); ([0006], [0012], [0031]-[0032]), and a cargo molecule, wherein the membrane-associated agent and the cargo molecule are configured to be transferred to an acceptor cell; wherein at least one of the membrane-associated moiety, extracellular moiety, intracellular moiety, or the cargo molecule is exogenous to the plurality of donor cells [0048], [0080], [0105], and wherein the plurality of donor cells transfers a detectable amount or a biologically effective amount of the membrane-associated agent and/or the cargo molecule to a plurality of acceptor cells [0006].
Regarding claim 91, Tanja teaches that the plurality of donor cells is stimulated (treated with proliferation inhibitor) prior to the contacting step [0039].
Accordingly, Tanja anticipates the instant claims 80, 88, 91, 97 and 98.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 06 July 2026 are acknowledged.
Applicant argues that Tanja relates to "a method for quantitative analysis of transport processes between cells," but does not disclose an exogenous cargo molecule as recited in currently amended claim 80. In contrast, Tanja "transfected the transferrin receptor fused to mCherry (Tf-RmCherry) in HeLa-Kyoto cells." Thus, Tanja relates to a peptide bond as found in a fusion protein in contrast to the instant definition of cargo molecule, which refers to a non-covalent association, a non-peptide bond, or not being associated with the membrane-associated agent. See remark p. 9 last three ¶.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a peptide bond as found in a fusion protein) are not recited in the rejected claim(s). MPEP 2145 states “Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993)”.
Applicant's arguments have been fully considered but they are not persuasive. In here, Tanja discloses a method for quantitative analysis of contact-dependent cell-to-cell molecular communication and transfer between cells, the method comprising obtaining of first singularized cells containing or expressing one or more traceable substances to provide donor cells [0006]. Tanja further specifies that the composition comprising a plurality of donor cells, the plurality of donor cells comprising a membrane-associated agent, the agent comprising: a membrane- associated moiety, and one or both of an extracellular moiety or an intracellular moiety (donor cells containing one more traceable substances are provided in the invention wherein traceable substance adhere to the external plasma membrane (traceable substance are the membrane associated extracellular moieties which can be selected from the group consisting of cell vesicles, protein aggregates, mRNA, microRNA, DNA, or nanoparticles); ([0006], [0012], [0031]-[0032]), and a cargo molecule, wherein the membrane-associated agent and the cargo molecule are configured to be transferred to an acceptor cell; wherein at least one of the membrane-associated moiety, extracellular moiety, intracellular moiety, or the cargo molecule is exogenous to the plurality of donor cells [0048], [0080], [0105], and wherein the plurality of donor cells transfers a detectable amount or a biologically effective amount of the membrane-associated agent and/or the cargo molecule to a plurality of acceptor cells [0006].
Maintained 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 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 80, and 88-105 are rejected under 35 U.S.C. 103 as being unpatentable over Tanja et al., (EP2876441B1; Pub. Date: 25 Oct. 2017; cited in IDS filed 06/12/2023; hereinafter “Tanja”), in view of Lim et al., (US2019/0202918A1, Pub. Date: Jul. 4, 2019; cited in IDS filed 06/12/2023; hereinafter “Lim”) in combination with Maltzahn et al. (WO 2020/102578; Pub. Date: May 22, 2020; cited in IDS filed 06/12/2023; hereinafter “Maltzahn”). This rejection is maintained for reasons of record and further explained below.
As discussed previously, regarding claims 80, 88, 91, 97 and 98, Tanja discloses a method of modifying an acceptor cell comprising contacting the acceptor with a composition comprising a plurality of donor cells under conditions suitable for transfer of membrane-associated agent and/or cargo molecule to the acceptor cell.
[AltContent: textbox ([img-media_image1.png]
Fig. 1 of Lim)]With respect to claims 89, Tanja does not disclose the protease cleavage site recognized by the protease. However, such was known in the prior art.
Regarding claims 89-90 and 96, Lim et al. disclose the ability to affect cellular signaling through recognition of a peptide-MHC by a cleavable chimeric Notch polypeptide, wherein the membrane-associated moiety or intracellular moiety comprises a protease cleavage site (abstract, [0009], [0246-0247]. As diagramed in Fig. 1, upon binding of the “sender cell” and “receiver cell”, the cleavable Notch polypeptide is cleaved releasing the intracellular portion which can affect intracellular processes including e.g., the expression of a transgene (e.g., "X" in FIG. 1) operatively linked to a promoter that is responsive to the freed intracellular domain [0390]. Therefore, the membrane-associated moiety or intracellular moiety comprises a protease cleavage site recognized by a protease that is not expressed in the plurality of donor cells (chimeric polypeptide (membrane associated moiety) of sender cells (donor cells) includes cleavable notch receptor polypeptide which comprises protease cleavage site which gets cleaved by the protease at c-terminal end; paragraph ([0009], [0246], [0390]).
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to POSITA at the time of the filling to combine the Tanja invention to recognize the protease cleavage site present in the donor cell to be recognized by the protease as taught by Lim in order to modulate various cellular processes following a cleavage event [0421].
Regarding claims 92-93, Lim discloses wherein the extracellular moiety comprises a targeting domain that binds to a first target cell moiety and a second target cell moiety and wherein the acceptor cell comprises the first target cell moiety or the second target cell moiety but not both (chimeric polypeptides is designed that include a cleavable notch polypeptide linked to an extracellular domain that includes a specific binding member that specifically binds to a peptide-MHC of an intracellular antigen of a sender cell (donor cell) wherein the extracellular domain of a chimeric polypeptide expressed by a receiver cell (target cell) binds the peptide-MHC of the sender cell (donor cell); paragraph [0390], figure1) It would have been obvious to one of ordinary skills in the art at the time of the invention to modify the Tanja invention to incorporate the cargo molecule in the composition and to disclose the binding of an extracellular moiety with the target domain as taught by Lim in order to study the binding between the extracellular moiety of the donor cell to that of the target cell receptors.
With respect to claims 94, Lim does not disclose expression of nucleic acid in the acceptor cell. However, such was known in the prior art.
Regarding claims 94-95 and 103-105, Maltzahn disclose the method comprises delivering fusosomes and their use to deliver membrane proteins to target cells (acceptor cells), wherein the fusosome comprises a lipid bilayer, and a cargo comprise a protein or nucleic acid encoding the protein such that target cell produces that protein and localizes it to the membrane protein (p. 1 Summary ¶), wherein the acceptor cells do not substantially express a nucleic acid encoding the membrane-associated agent ([000376], [000421] of Maltzahn) or, if a cargo molecule is present in acceptor cells, do not substantially express a nucleic acid encoding the cargo molecule. Furthermore, Maltzahn disclose fusosomes (e.g., donor cells) are autologous and/or allogeneic to the acceptor cell ([00052], [000128], p. 70 see 196¶, p. 1491st ¶).
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. It would have been obvious to POSITA at the time of the invention to include the Tanja invention to transfer the nucleic acid or membrane associated agent by means of a cargo molecule as taught by Maltzahn in order to transiently modify gene expression in the target cell or to modify the expression of the membrane protein in the target cell (p. 493 Example 55, [000186], [000331] of Maltzahn).
Regarding claim 99, Lim disclose that the ability to affect cellular signaling through recognition of a peptide-MHC by a cleavable chimeric Notch polypeptide, wherein the membrane-associated moiety or intracellular moiety comprises a protease cleavage site (abstract, [0009], [0246-0247], Fig. 1). Lim’s method generally involves contacting the cell with the binding partner of the specific binding member of a chimeric polypeptide of the present disclosure. Such binding induces cleavage of the Notch receptor polypeptide at the one or more proteolytic cleavage sites, thereby releasing the intracellular domain Release of the intracellular domain may modulate an activity of the cell, e.g., induce expression of a heterologous gene or coding sequence ([0332]-[0333] of Lim). Therefore, Lim’s modulating a level or activity of a molecule in the acceptor cell or the plurality of acceptor cells; modulating enzyme activity in the acceptor cell or the plurality of acceptor cells; modulating a genetic or an epigenetic event in the acceptor cell or the plurality of acceptor cells; modulating acceptor cell differentiation; modulating acceptor cell reprogramming; activating a signaling pathway in the acceptor cell; and modifying cell adhesion and trafficking and modifying cell adhesion and trafficking ([0112]-[0115] of Lim).
Regarding claim 100, Lim disclose that the membrane-associated moiety is a transmembrane moiety that comprises a transmembrane domain from a receptor (i.e., Notch receptor) ([0187], [0208], [0301] of Lim).
Regarding claim 101, Lim disclose that the membrane-associated agent comprises the extracellular moiety, and the extracellular moiety comprises a targeting domain or a transfer promoting moiety ([0348], [0350] of Lim).
Regarding claim 102, Lim disclose that the membrane-associated agent comprises the intracellular moiety, and the intracellular moiety comprises a protein binding domain [0252]-[0255].
The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395; Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969). 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 teachings of Tanja et al. in view of Lim in combination with Maltzahn especially in the absence of unexpected results.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 06 July 2026 are acknowledged.
Applicant argues that currently amended, specifies that the plurality of donor cells comprises an exogenous cargo molecule, which is not taught or suggested by Tanja. Lim does not remedy the deficiencies of Tanja. Lim relates to "chimeric polypeptides which modulate various cellular processes following a cleavage event induced upon binding of a specific binding member of the polypeptide with its binding partner," and fails to teach or suggest transfer of a membrane associated agent from a plurality of donor cells to an acceptor cell, much less such a transfer where the donor cell comprises an exogenous cargo molecule as recited in instant claim 80. See remark p. 10 last ¶ to p. 11 1st ¶.
MPEP 2145 states “The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference.... Rather, the test is what the combined teachings of those references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Applicant's arguments have been fully considered but they are not persuasive. In here, Tanja discloses a method for quantitative analysis of contact-dependent cell-to-cell molecular communication and transfer between cells, the method comprising obtaining of first singularized cells containing or expressing one or more traceable substances to provide donor cells [0006]. Tanja further specifies that the at least one of the membrane-associated moiety, extracellular moiety, intracellular moiety, or the cargo molecule is exogenous (i.e., viral genome [0107], mRNA, microRNA, DNA, nanoparticles [0031]) to the plurality of donor cells (in one of the examples donor cells were transfected with the transferrin receptor-mCherry (transferrin receptor which are extracellular moiety is exogenously introduced to the donor cell) and in another example donor cells were transfected with proteins (proteins are membrane associated moiety which is exogenously introduced to the donor cell); paragraph [0048], [0080], [0105], Fig. 13B, C). Therefore, POSITA would have been anticipating at the time of the Tanji’s invention the membrane associated moiety presence in different level than donor cell, accordingly, POSITA could anticipate after contact a detectable amount of the membrane-associated agent (at least 1%) increase in the acceptor cells (Figs. 19 A-B). Accordingly, it would have been obvious to POSITA at the time of the filling to combine the Tanja invention to recognize the protease cleavage site present in the donor cell to be recognized by the protease as taught by Lim in order to modulate various cellular processes following a cleavage event ([0421] of Lim).
CONCLUSION
Applicant's 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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is (571)272-0196. The examiner can normally be reached M-F 8-5 (EST).
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
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