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 .
DETAILED ACTION
Claim status
Claims 1-3, 7-8, 17, 20, 24, 28, 30-31, 40, 44, 61, 83, and 88 are pending
Claims 3, 17, 20, 24, 28, 30 are withdrawn
Claims 1-2, 7-8, 31, 40, 44, 61, 83 and 88 are under examination
Election/Restrictions
Applicant’s election of the following invention without traverse in the reply filed on 4/20/2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Group I, Claims 1-3, 7-8, 17, 20, 24, 28, 30-31, 40, 44, 61, 83, and 88.
Applicant’s election of the following species without traverse is acknowledged.
CAR as the membrane associated agent
Claims 3, 17, 20, 24, 28, 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic claim.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 5/06/2024 and 4/20/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2, 31, 40, 61, 83 and 88 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Instant claim(s) is/are directed to a method of modifying an acceptor cells based on a natural process. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because they are not substantially more.
Briefly summarized here, the guidance for subject matter eligibility cites a two part test: is the claimed invention directed to a statutory class of invention (Step 1), if so then is the claimed invention as a whole directed to a law of nature, natural phenomena, or an abstract idea (i.e. set forth or described in the claim) (Step 2A, prong one), if so then is the claimed invention recite additional elements that integrate the judicial exception into a practical application (Step 2A, prong two), if not then does the claim as a whole amount to significantly more than the judicial exception (Step 2B).
In regard to Step 1, Claims 1 and 2 are drawn to a process, a method of modifying an acceptor cell.
In regard to Step 2A prong one, this part of the eligibility analysis evaluates whether the claim recites a judicial exception. Claims 1 and 2 recite the contacting of donor and acceptor cells, wherein the donor cell comprises a membrane-associated agent and the acceptor cell comprising a docking moiety that binds a cognate site on the membrane-associated agent. Claims 1 and 2 recite that the membrane-associated agent and/or cargo are transferred to the acceptor cell. Under its broadest reasonable interpretation consistent with the specification, the plain and ordinary meaning of these limitations require contacting an antigen presenting cell comprising a peptide bound MHC (i.e., donor cell with membrane-associated agent and cargo) and an acceptor T cell comprising a T-cell receptor for binding the MHC (acceptor cell with docking moiety). For example, the review of Dhainaut et al. (Frontier Immuno, 2014, 5:1-4) [AltContent: textbox ([img-media_image1.png])]teaches that dendritic cells (DC) contact T cells through a peptide-MHC complex, which results in the transfer of the peptide-MHC molecules to the acceptor T cells (see excerpt of Fig. 1, adjacent). As this “contacting” step simply requires the process of antigen presentation, the limitation falls into the “natural process” grouping of natural phenomena because the method can be practically performed in a subject with an adaptive immune system. Thus, the claim(s) are directed to the judicial exception of (a mathematical concept-type abstract idea, a mental process-type abstract idea, and a law of nature) (Step 2A, Prong One: YES).
In regard to Step 2A, prong two: this part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception. In the present situation, although Claims 1 and 61 recite the cargo is “exogenous”, Dhainaut evidences and it was well known that DC present a variety of naturally occurring non-self antigens such as viral peptides (see p.1, last para.). Furthermore, although Claim 2 indicates that the donor cell comprises the cargo at a different level than its source cell type, since DCs are derived from hematopoietic stem cells, any peptide antigen non-covalently bound to the MHC on the DC would have naturally been at a different level. Thus, even when considering the elements in combination, the claim(s) as a whole do not meaningfully integrate the recited exception into a practical application (Step 2A, prong two: No).
In regard to Step 2B, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
As stated supra, additional elements such as an “exogenous” cargo were considered to encompass naturally occurring antigen peptides during antigen presentation. Furthermore, the additional element of “contacting” the acceptor cell in a subject is encompassed by a subject with an adaptive immune system.
Consequently, for the reasons discussed above, the additional elements individually or in combination with the judicial exception do not provide an inventive concept; so, the claim as a whole does not amount to significantly more than a generic instruction of “contacting” the judicial exceptions. (Step 2B: NO).
For the reasons set forth above, the claims are not considered to recite something significantly different than a judicial exception and thereby are not directed to patent eligible subject matter.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 31, 40, 44, 61, 83 and 88 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Von Maltzahn et al., (WO2020/014209, filed 7/09/2019, published 1/16/2020).
With respect to claims 1 and 2, Von Maltzahn teach a method of delivering an exogenous cargo from a donor cell to an acceptor cell wherein
The donor cells is an enucleated cell (e.g., HEK-293T) comprising
A membrane-associated agent such as VSV-G, which comprise (i) a transmembrane domain, (ii) an extracellular docking moiety that specifically binds LDL receptors, (iii) an intracellular moiety (p. 444, Example 69);
An exogenous cargo such as the Cre recombinase protein; wherein
The acceptor cell expresses an docking moiety that binds the membrane-associated agent (e.g., the LDL-receptor),
wherein after the transfer the acceptor cell comprises an increased amount of the cargo such as increased Cre recombinase as measured by increased fluorescence (p. 458, Example 81).
Specifically, in regard to claim 2, Von Maltzahn teaches the Cre protein is loaded into the donor cells after enucleation (see Example 80), and thus the cargo molecule is present at a different level in the donor cell than the nucleated source cell.
In regard to claim 31, as stated supra, the cargo can be a protein such as the Cre protein.
In regard to claim 40, in one embodiment, the donor cell is administered to a subject, wherein the fusosomes are produced from cells that stably express firefly luciferase, and the acceptor cells are comprised in the subject and exhibit increased bioluminescence post administration (see Example 47, p. 421-422).
In regard to claim 44, in another embodiment, Von teaches that the donor cell can be modified to fuse and deliver cargo to a specific target cell. Specifically, Von uses a chimeric antigen receptor comprising a hemagglutinin glycoprotein of measles virus (MvH) and the fusion protein F, wherein the MvH is fused to an scFv designed to target CD8, and HEK acceptor cells expressing CD8 (p. 446-447, Example 72, Measuring fusion with a target cell). Note that Applicant’s specification broadly defines a CAR as a recombinant polypeptide construct comprising an antigen binding domain, transmembrane domain, and intracellular moiety that may or may not comprise a signaling domain [00195]. Thus, the donor cells comprises chimeric MvH(CD8) receptor that comprises an N-terminal cytoplasmic tail, transmembrane domain, and anti-CD8 scFV, while the acceptor cells comprise a CD8 binding moiety.
In regard to claim 61, as stated supra, the cargo (e.g., Cre protein, luciferase) are exogenous to both the donor and acceptor cells.
In regard to claim 83, the acceptor cells are not cancer cells, but cells that express the VSV-G receptor (e.g., LDL receptor) (see Example 47) or are HEK cells that express CD8 (see Example 72).
In regard to claim 88, as stated supra, Von Maltzahn teaches the cargo molecule is firefly luciferase, wherein the fusosomes were produced from cells that stably expressed firefly luciferase. Thus, cargo molecules would naturally include firefly luciferase mRNA. Furthermore, Von Maltzahn explicitly teaches that the fusosomes comprise an exogenous mRNA (p. 293, para. xi, p. 297, para. vi, p.301 para. xvii, p. 306, last para., p. 318, 2nd para., p. 319, 3rd para.).
Accordingly, VonMaltzahn anticipates instant claims.
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 7-8 and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Von Maltzahn et al., (WO2020/014209, filed 7/09/2019, published 1/16/2020), in view of Amirache et al., (Blood, 2014, 9:1422-1424).
As discussed previously, Von Maltzahn teaches a method of transferring cargo from a donor cell to an acceptor cell.
However, although Von Maltzahn suggest the source cell is a lymphocyte (p. 291, Example 45, p. 347, line 27), and contemplate the use of the Jurkat T cell line (p. 145, 1st and last para., p. 146, 2nd , 3rd, and 4th para., p. 147, 3rd para., p. 148-149 para. a-e, p. 150 para. e, g, h, p.305, Example 26, para e), they are silent with respect to an activated T cell as the donor cell.
Amirache teaches methods of transducing T cells with VSV-G pseudotyped lentiviral vectors. Specifically, Amirache teaches that T cells must first be activated before transduction so as to up regulate the LDL receptor (p. 1422, Fig. 1).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to choose a T cell as suggested by Von Maltzahn, and to pre-activate the T cell before transduction as taught by Amirache with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Amirache because quiescent T cell do not express the LDL receptor and are poorly transduced by lentiviral vectors. Furthermore, in regard to choosing activated T cells as the donor cells, one of ordinary skill would have been motivated to do as taught by Von Maltzahn because of their homing capabilities (p. 421, Example 47).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-2, 31, 40, 61, 83 and 88 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 80, 87-105 of copending Application No. 18/010,857. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the method of modifying an acceptor cell anticipates the method of instant application. It is clear that elements of the cited application claims are to be found in instant claims. The difference between the cited application claims and the instant claims lies in the fact that the cited application claims use a plurality of donor cells. Thus the invention of said claims of the cited application are in effect “species” of the “generic” invention of the instant claim. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by cited application claims, said claims are not patentably distinct.
Claims 1-2, 31, 40, 61, 83 and 88 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-18 and 22 of copending Application No. 18/723,205. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the method of modifying an acceptor cell anticipates the method of instant application. It is clear that elements of the cited application claims are to be found in instant claims. The difference between the cited application claims and the instant claims lies in the fact that the cited application claims are more specific to the donor cells. Thus the invention of said claims of the cited application are in effect “species” of the “generic” invention of the instant claim. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by cited application claims, said claims are not patentably distinct.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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