DETAILED ACTION
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 and remarks, filed 5/4/26, are acknowledged.
Claims 158-171 have been amended.
Claims 158-177 are pending.
Claims 172-177 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 158-171 are being acted upon
The rejections under 35 U.S.C. 112a and 112b are withdrawn in view of Applicant’s claim amendments.
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 158-171 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon (product of nature) without significantly more. The claim(s) recite(s) a genetically engineered human cell. This judicial exception is not integrated into a practical application because said cells do not include additional elements that are sufficient to amount to significantly more than a product of nature.
The present claims are directed to a cellular vaccine comprising a human cell. However, the recitation of a “cellular vaccine” refers to an intended use. The limitation, recited at a high level of generality, amounts to nothing more than field of use and does not impart any markedly different structure or function from naturally occurring cells.. Naturally occurring human cells are known to carry genomic disruption in HLA genes. See Hazini for example, which teaches that molecular gene defects and HLA genetic mutations are common in cancer. See also Goktas which teaches that genetic mutations and loss of MHC and other genes such as RFX5 occur naturally in human subjects and cells therein. Furthermore, the HLA genetic locus is inherently polymorphic, and each individual’s HLA-DP gene will exhibit numerous changes in the genetic sequence encoding the proteins, with respect to each other, that result in function differences in the resulting protein such as differing peptide binding capacities. Thus, any human cell would have genetic variation or mutations in HLA genes as compared to other human cells, and would be within the scope of a “genomic disruption” in HLA. Regarding the limitation in the claims that the cells express an “exogenous” nucleic acid, it is noted that this refers to a product by process limitation for how the cells are produced. During examination, a product-by-process claim is not limited to manipulations of the recited steps, but instead is only limited to the structure implied by the steps. However, nothing in the claims implies or recites any structural element (for example a viral vector comprising the nucleic acid) that would distinguish from a naturally occurring cells. Naturally occurring tumor cells or APC would comprise nucleic acids encoding various cell surface proteins that are within the scope of the instant claims. For example, the naturally occurring APCs having RFX5 deletion in Goktas would also comprise nucleic acids encoding cell surface costimulatory molecules, which are within the claim scope. Furthermore, as taught by Groh, tumor cells inherently comprising nucleic acids for MICA. Regarding the claimed limitation that the cells further comprise a nucleic acid encoding a viral antigenic protein, it is noted that naturally occurring cells also comprising viral nucleic acids during physiological process, such as viral infection. For example, see Tan which teaches naturally occurring EBV transformed B cell malignances which are also genetically deficient in HLA expression (and would naturally comprise, and express various costimulatory molecules or MICA). Thus, the claimed human cells are not markedly different in structure or function from those that are naturally occurring.
Applicant’s arguments filed 5/4/26 have been fully considered, but they are not persuasive.
Applicant argues that the amendment overcome the rejection. However, as noted above, the recitation of a “cellular vaccine” refers to an intended use. The limitation, recited at a high level of generality, amounts to nothing more than field of use and does not impart any markedly different structure or function from naturally occurring cells..
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.
Claim(s) 158-171 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Steinle, 2001, as evidenced by Zemmour, 1992.
Steinle teaches a C1R B human cell line genetically engineered to express an exogenous MICA at the cell surface (i.e. a cell surface protein that binds to NKG2D on NK cells and activates cytolytic activity of NK cells, see page 280 and Fig. 1, in particular). As evidenced by Zemmour, said C1R cells are EBV transformed (i.e. the comprise a nucleic acid encoding an exogenous EBV surface, secreted, or cytoplasmic antigen), and also have a genomic disruption in an HLA gene. In particular, Zemmour teaches that said C1R has a deletion in the entire HLA region from one haplotype, including HLA-II (i.e. a genomic disruption in HLA-DP, DR, and DQ, see page 1941, 1947, and Fig. 1, in particular). Regarding the limitation of a cellular vaccine or that administration of the genetically engineered human cell to a subject immunizes the subject to an antigen, this refers to an intended use. The cells of the prior art are structurally identical to those of the instant claims and they would be capable of performing the intended use.
Claim 161 is included in the rejection to the extent that the transcriptional regulator is still recited in the alternative. For example, incorporation of claim 161 into claim 158 would result in claim for a cell comprising a genomic disruption in an HLA gene or a transcriptional regulator, wherein the transcriptional regulator is CIITA. Amendment to claim 161 to recite the genetically engineered human cell of claim 158, wherein the cell comprises a genomic disruption in at least one transcriptional regulator of an HLA gene, for example, would overcome the anticipation rejection of claim 161 by Steinle.
Applicant’s arguments filed 5/4/26 have been fully considered, but they are not persuasive.
Applicant argues that the reference does not teach a cellular vaccine or that administration of the cell to a subject immunizes the subject to an antigen. Applicant argues that these are functional limitations that must be considered.
As noted above, the prior art cells are structurally identical to those of the instant claims and the cells would have the same functional limitations. See MPEP 2112.01, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.
Although the prior art does not actually use the cells for immunization or as a cellular vaccine, doing so is merely an intended use of the claimed product and the product of the prior art is structurally and functionally identical to that of the instant claims.
Claim(s) 158-171 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by WO 2020/072700, as evidenced by Liu, 2018.
WO 2020/072700 teaches genetically engineered human cells that are engineered to comprise a nucleic acid encoding a single HLA allele (see page 25-27, and Fig. 5 in particular). WO 2020/072700 teaches that the cells can be engineered to be deficient in HLA by deleting endogenous HLA-I and HLA-II alleles, which include HLA-DP, by CRIPSR-Cas9 mediated genome editing (i.e. a genomic disruption, see page 25 and 26, in particular). WO 2020/072700 teaches that the cells are infected with a virus in order to identify HLA binding viral peptide, and teaches DNA or RNA viruses such as SARS coronavirus (i.e. they comprise a nucleic acid encoding a microbial antigen peptide, see page 36 and 39, in particular). WO 2020/072700 teaches that said introduced HLA allele presents said viral peptide and induces killer T cell responses (i.e. it is a cell surface protein that binds to and activates cytolytic immune cells, see Fig. 1, in particular). Regarding the limitation that administration of the genetically engineered human cell to a subject immunizes the subject to an antigen, this refers to an intended use. The cells of the prior art are structurally identical to those of the instant claims and they would be capable of performing the intended use.
Regarding claim 162, which requires that the exogenous nucleic acid encodes a cell surface protein that binds to a protein on the surface of an NK cell, WO 2020/072700 also teaches that the genetically engineered cells can be, for example B or dendritic cells (See page 26). B cells and dendritic cells inherently comprise nucleic acids encoding various cell surface costimulatory molecules that can bind to and activate NK cells. Regarding the recitation that the nucleic acid is “exogenous” this merely refers to a product by product limitation, i.e. that the cell is produced by introducing an exogenous nucleic acid. However, the patentability of a product does not depend on its method of production in the absence of a structural difference. In the instant case, the genetically engineered cells of WO 2020/072700 comprise a nucleic acid encoding a cell surface protein (such as a costimulatory molecule) that is structurally and functionally identical to that of the instant claims and meets the limitations of the present claims. Regarding claim 163, the cells would inherently comprise a nucleic acid encoding MICA, and WO 2020/072700 also specifically teaches that the genetically engineered cells can be subjected to stress (see page 26). As evidenced by Liu, MICA is specifically upregulated in stressed cells, and therefore cell surface expression of MICA would also be an inherently property of the genetically engineered cells of WO 2020/072700.
Claim 161 is included in the rejection to the extent that the transcriptional regulator, as it depends from claim 158, is recited in the alternative for the same reasons set forth above.
Applicant’s arguments filed 5/4/26 have been fully considered, but they are not persuasive.
Applicant argues that the claims are not anticipated for the same reasons set forth above.
The claims stand rejected for the same reasons set forth above.
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.
Claim 158-171 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/072700, in view of Liu, 2018 and Xu, April 4, 1019.
The teachings of WO 2020/072700 are described.
The reference differs from the claimed invention in that it does not explicitly teach a genomic disruption in CIITA.
Xu teaches that disruption of class II HLA expression can be performed by deleting the CIITA gene, and that functional loss of CIITA gene leads to MHC class II deficiency. Xu explains that CIITA is a transcription factor that is essential for transcription of class II HLA genes, and that functional loss of CIITA leads to HLA-II deficiency (i.e. loss of all HLA-II alleles expression, including HLA-DP, see page 571, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to produce the HLA-II deficient cells in WO 2020/072700, by deleting CIITA, as taught by Xu. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because Xu teaches that CIITA is a transcription factor that is essential for transcription of all class II HLA genes, and that functional loss of CIITA leads to HLA-II deficiency. Thus, it would be obvious to produce the cells of WO 2020/072700 that are engineered human cells that are engineered to express an single HLA allele (which meets part b. of the instant claim 158 and 166) and which is also infected with a DNA or RNA viruses such as SARS (i.e. part c. in claim 166), and which is further engineered to be have a genomic deletion in CIITA, as taught by Xu, to provide for HLA-II deficiency (i.e. part a of claims 158 and 166). As WO 2020/072700 further teaches that the cells can be subjected to stress, it would be obvious that the cells would also express MICA, encoded from a nucleic acid within the cells, as taught by Liu. As noted above, the limitation of an “exogenous” nucleic acid is a product by process limitation that does not distinguish the claimed cells from those made obvious by the prior art.
Applicant’s arguments filed 5/4/26 have been fully considered, but they are not persuasive.
Applicant argues that the claims are not obvious for the same reasons set forth above.
The claims stand rejected for the same reasons set forth above.
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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 158-171 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 and 22-23 of copending Application No. 18/757,948 (reference application), in view of WO 2020/072700 and Steinle, 2001. Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘948 application claims a genetically engineered human cell comprising a genomic disruption in an HLA gene, such as HLA-DP, or a transcriptional regulator of an HLA gene, such as CIITA, and an exogenous nucleic acid encoding a cell surface protein that binds to a protein expressed on the surface of a phagocytic or immune cell, wherein binding activates phagocytic or cytolytic activity, and wherein the cell overexpressed ARRDC1. Thus, the genetically modified cells of the ‘948 application represent a species of the genus of cells encompassed by the present claims. The ‘948 application claims that the cell further comprises a nucleic acid encoding an exogenous protein, such as a microbial protein, and selecting from known microbial proteins for expression, such as viral proteins as taught by WO 2020/072700 would be well within the purview of the ordinary artisan. Furthermore, it would be obvious to select MICA as the cell surface protein, since Steinle teaches that it can be expressed by genetic engineering and that it functions to activate cytolytic NK cell activity. Regarding the limitation of a cellular vaccine, this is an intended use and the cells of the copending application inherently are capable of acting as a cellular vaccine since they are structurally identical to those of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s statement that the rejections be held in abeyance until the time of allowance is acknowledged.
No claim is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
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) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
Prosecution Insights