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
Claims 1-16 were previously pending as per claims filed on 08/30/2024.
Applicant’s election without traverse of the species of human vascular endothelial cells and cell therapeutic composition in the reply filed on 22 September 2026 is acknowledged. After further consideration, the requirement for an election of species between the cells is withdrawn as examination of all cell species together does not represent undue burden. The elected species of cell therapeutic composition is being applied to all pending claims.
No claim amendments are presented.
Therefore, claims 1-16 as elected are pending and under examination in the present Official Action.
Priority
The present application is a continuation of International Application No. PCT/KR2023/003055, filed 06 March 2023, which claims priority to Republic of Korea Application No. KR10-2022-0027931, filed 04 March 2022. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified untranslated copies of papers required by 37 CFR 1.55 have been received from the World Intellectual Property Organization on 20 February 2026.
The earliest possible priority for the instant application is 04 March 2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 30 August 2024, 09 April 2026, and 23 July 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings are objected to because FIG. 2 is out of focus and illegible. 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.
Claim Objections
Claims 1-3, 5, and 7 are objected to because of the following informalities: the claims inconsistently use the plural and singular conjugated forms of the word “gene”. For example: claim 1 requires “artificially engineered genes” while dependent claim 2 refers to “a gene”. Appropriate correction is required.
Claims 1-2, 4-5, 7, 9, and 12 are objected to because of the following informalities: abbreviations/acronyms need to be spelled out upon their first encounter in the claims. For example: “LGALS9 (Gal-9)”. “CLEC4G (LSECtin)”, “PD-L1”, “HHLA2”, and “PSC”. Appropriate correction is required.
Claim 6 is objected to because of the following informalities: The claim unnecessarily recites “one” between “are” and “selected” in the second line of the claim in a manner that convolutes the language of the claim. Appropriate correction is required.
Claim 7 is objected to because of the following informalities: the claim inappropriately uses the pluralized form of the word “claim” in the first line of the claim. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: The claim unnecessarily recites “one” between “are” and “selected” in the first line of the claim in a manner that convolutes the language of the claim. Appropriate correction is required.
Claim 10 is objected to because of the following informalities: the claim inappropriately uses the pluralized form of the word “claim” in the second line of the claim. Appropriate correction is required.
Claim 1 is objected to because of the following informalities: the claim is missing a definite article (for example “the”) before the word “genome” in line three of the claim. Appropriate correction is required.
Claim 2 is objected to because of the following informalities: the claim repeats the same Markush group of immune activity inhibitory factors twice in an identical fashion resulting in redundancy in the claim. Appropriate correction is required.
Claim 2 is objected to because of the following informalities: the claim recites “a gene encoding…” in the third line of the claim when claim 1 from which claim 2 depends already recites this limitation for the first time. Therefore, claim 2 should recite “the” in this position instead. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite in its recitation of “cells derived from stem cells”. The claim is vague and indefinite in that the metes and bounds of the term “derived from” are unclear. It is unclear the nature and number of steps required to obtained a “derivative” of a stem cell. The term implies a number of different steps that may or may not result in a change in the functional characteristics of the cells from the source that they are “derived from”. Further, it is unclear how much similarity a cell must have to a stem cell to be considered derived from that stem cell. Thus, a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought in claim 1. This rejection could be overcome by deleting the quoted language since the claim already presents “cells differentiated from stem cells”. Claims 2-16 are further rejected for their dependency on a rejected base claim.
Claim 2 recites the limitation "the gene sequence of the artificially engineered cells is different from the gene sequence of wild-type cells" in the first and second lines of the claim. There is insufficient antecedent basis for these limitations in the claim. Nowhere in claim 1 from which claim 2 depends is “a gene sequence” recited for the artificially engineered cells nor for wild-type cells (which themselves are presented for the first time in claim 2). Accordingly, the metes and bounds of claim 2 cannot be determined and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought.
The term “with increase in the expression or activity” in claim 2 is a relative term which renders the claim indefinite. The term “with increase in the expression or activity” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear how much expression or activity must be increased to be considered increased within the meaning of the claim. Further, to describe cells as being “with increase” is unclear in itself as it is unclear if the claim actually requires the claims to possess increased expression or activity or rather to require them to have the latent ability to present increased expression or activity. This rejection could be overcome by amending claim 2 to recite wherein the expression or activity of the genes encoding one or more immune activity inhibitory factors is higher in the artificially engineered cells than in the wild-type equivalent of the artificially engineered cells.
The term “a high mRNA expression level” in claim 3 is a relative term which renders the claim indefinite. The term “a high mRNA expression level” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. While the claim does recite “compared to the expression level of mRNA transcribed from genes in the wild-type cells,” the claim does not require the expression level to be higher than that in wild-type cells. Consequently, it is unclear how high an expression level must be to fall within the scope of claim 3. This issue is compounded by the fact that it is unclear which “genes” in wild-type cells are the reference point for comparison in claim 3. Conceivably any gene within any wild-type cell (not even the required to be the wild-type equivalent of the engineered cell) could be used for comparison. Consequently, the metes and bounds of claim 3 cannot be determined and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought in claim 3.
Claim 3 is further rejected because “the artificially engineered gene”, “the expression level of mRNA transcribed from genes” and “the wild-type cells” all lack proper antecedent basis in the claims. Each of these recitations is set forth for the first time in claim 3. Accordingly, the metes and bounds of claim 3 cannot be determined and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought.
Claim 5 recites “the gene” and “the cells genomes” in the first and third lines of the claim respectively. There is insufficient antecedent basis for either of these limitations in the claims because each of these recitations is set forth for the first time in claim 5. Claim 1 from which claim 5 depends recites “genes” (plural) and “genome of cells” (singular). Accordingly, the metes and bounds of claim 5 cannot be determined and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought.
Claim 6 is indefinite in its recitation of “cells derived from stem cells”. The claim is vague and indefinite in that the metes and bounds of the term “derived from” are unclear. It is unclear the nature and number of steps required to obtained a “derivative” of a stem cell. The term implies a number of different steps that may or may not result in a change in the functional characteristics of the cells from the source that they are “derived from”. Further, it is unclear how much similarity a cell must have to a stem cell to be considered derived from that stem cell. Thus, a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought in claim 6. This rejection could be overcome by deleting the quoted language since the claim already presents “cells differentiated from stem cells”.
Claim 7 is indefinite in its recitation of “cells derived from the artificially engineered cells”. The claim is vague and indefinite in that the metes and bounds of the term “derived from” are unclear. It is unclear the nature and number of steps required to obtained a “derivative” of an artificially engineered cell. The term implies a number of different steps that may or may not result in a change in the functional characteristics of the cells from the source that they are “derived from”. Further, it is unclear how much similarity a cell must have to an artificially engineered cell to be considered derived from that cell. Thus, a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought in claim 7. This rejection could be overcome by deleting the quoted language since the claim already presents “cells differentiated from artificially engineered cells”.
Claim 8 recites “the cells” in the first line of the claim. There is insufficient antecedent basis for this limitation in the claims because claim 7 from which claim 8 depends recites three possible cells to which claim 8 could be referring (cells differentiated or derived from the artificially engineered cells, the artificially engineered cells, and stem cells). Accordingly, the metes and bounds of claim 8 cannot be determined and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought.
Claim 13 is indefinite in its recitation of “cells derived from stem cells”. The claim is vague and indefinite in that the metes and bounds of the term “derived from” are unclear. It is unclear the nature and number of steps required to obtained a “derivative” of a stem cell. The term implies a number of different steps that may or may not result in a change in the functional characteristics of the cells from the source that they are “derived from”. Further, it is unclear how much similarity a cell must have to a stem cell to be considered derived from that stem cell. Thus, a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought in claim 13. This rejection could be overcome by deleting the quoted language since the claim already presents “cells differentiated from stem cells”.
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 1-16 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 claim(s) contains 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 inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims broadly encompass the insertion of one or more of Gal-9, LSECtin, PD-L1, and HHLA2 into any location in the genome of any cells. This genus of cells encompasses genomic insertions which disrupt genes vital for survival as well as genomic insertions to loci in which no appreciable expression of the inserted genes would be observed. In addition, the claims do not even require the utilization of a promoter at the insertion site or the use of a promoter to drive expression at all. The claims require the functional property of hypo immunogenicity of the cells through the requirement that the cells have increased expression of “immune inhibitory factors” as well as the title of the invention proclaiming the cells as hypoimmunogenic. Yet the only structures associated with this function are the genes themselves, no promoters, no particular insertion site. In addition, the claims encompass cells which have no DNA to be modified like red blood cells which expel their nucleus during development (RBCs are cells differentiated or derived from stem cells), and recalcitrant cells like non-dividing cells which are not capable of genetic modification in themselves with current technology (cells like mature neurons and skeletal muscle cells).
The working examples teach the knock in of Gal-9, CLEC4G, and HHLA2 into iPSCs at the AAVS1 locus ([0146]). The working examples teach that insertion at this site results in increased mRNA levels for the inserted genes ([0153]). The working examples also teach Gal-9 and CLEC4G inserted individually, Gal-9 and CLEC4G inserted together without HHLA2, and Gal-9, CLEC4G, and PD-L1 inserted together ([0171]). While the specification teaches a cassette with all four genes (FIG. 1), this cassette does not appear to have been used to produce cells expressing all four genes at once (since no working example is provided for this possibility. Further, the specification is silent as to where exactly the genes were inserted for the combinations in para. 171. Thus, the working examples only teach the insertion of Gal-9, CLEC4G, and HHLA2 into the AAVS1 genomic locus. While other combinations are taught, no working example is provided in which each of the four genes is inserted and the specification is silent as to where exactly the further combinations were inserted. Further, no working example is provided in which any cells other than iPSCs are genetically modified to express the genes.
The specification does teach other sites for insertion of genes, however this teaching is limited to known safe harbor sites (CCR5, CLYBL, ROSA26, SHS231) and no location other than these four safe harbor sites along with AAVS1 is taught for insertion. No working example is even provided for the insertion of anything into any site other than AAVS1.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021). Further, 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 AbbVie 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."). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). See MPEP 2163(II)(A)(3)(a)(ii).
Here, the working examples only teach iPSCs as the cells to be modified and only teach AAVS1 as the genomic locus for insertion. Nowhere in the specification is there an insertion of all four of the claimed genes into any locus at the same time. In addition, these are the only cells taught as having the claimed functional property. Therefore, to the extent a structure/function relationship exists in the instant claims, it is only with regard to either (1) Gal-9, CLEC4G, and HHLA2, (2) Gal-9, (3) CLEC4G, (4), Gal-9 and CLEC4G together without HHLA2, or (5) Gal-9, CLEC4G, and PD-L1 inserted into either the AAVS1, CCR5, CLYBL, ROSA26, or SHS231 genomic locus of a stem cell. In addition, the claims encompass inoperative embodiments in encompassing insertion sites which would disrupt the expression of vital genes and insertion sites outside of the known safe harbor sites taught in the specification as well as encompassing cells which are biologically incapable of genetic modification (RBCs) and recalcitrant fully differentiated cell types.
Accordingly, the supporting disclosure would not represent to the skilled artisan at the time of filing that Applicant had possession of a representative number of species for the entire genus claimed.
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 1-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims are drawn to cells and cell therapeutic compositions comprising cells. The cell is not required to be isolated. The specification teaches that the invention is intended to inhibit “immune rejection upon transplantation” (Abstract). Thus, the invention is intended to be given to humans as a therapy and the broadest reasonable interpretation of the cell (invention) encompasses a cell in a living human being. A cell in a human being is integral to the human being. Therefore, claims 1-16 are broadly, but reasonably, interpreted to encompass a living human being or more particularly an integral component of a living human being. Were the cell readily separable from the human being, as might be an item of clothing, perhaps the claims would not read on non-statutory subject matter (i.e., a living human being), but, here, that is clearly not the case. M.P.E.P. § 2105 states:
If the broadest reasonable interpretation of the claimed invention as a whole
encompasses a human being, then a rejection under 35 U.S.C. 101 must be made
indicating that the claimed invention is directed to nonstatutory subject matter.
It is suggested that this issue might best be remedied by amending claims 1-16 to recite the limitation, “isolated” before “artificially engineered cells”, “cells”, “stem cells”, etc. (wherever appropriate).
Claims 1-16 are further rejected under 35 U.S.C. 101 because the claimed invention is or includes subject matter that is not patent eligible. The claims do not recite something significantly different than a judicial exception when the claims are analyzed as a whole. The rationale for this determination is explained below.
The claims are directed to a judicial exception to 35 U.S.C. § 101, namely a cell, which, absent a showing otherwise, is deemed to be indistinct from naturally occurring cell. To the extent the claims specify a particular cell, they specify that the cell is a stem cell, a cell differentiated from a stem cell, or a cell derived from a stem cell which is “artificially engineered” to have Gal-9, LSECtin, PD-L1, and/or HHLA2 inserted into their genome. This language encompasses any possible cell known or yet to be discovered which has one of the genes in question inserted into its native site in the genome because virtually every cell is a cell differentiated from a stem cell. Encompassed within the claimed “differentiated cell” is, for example, a T cell having PD-L1 inserted into the genome in place of the native PD-L1 whose closest natural counterpart would be a naturally occurring T cell which itself expresses PD-L1 (See Francisco et al., Journal of Experimental Medicine 206.13 (2009): 3015-3029). Therefore, the claims encompass T cells as they occur in nature. To be clear, this is because, as written, the claims do not sufficiently distinguish the invention from a product that exists naturally; and moreover, whether isolated or not, it is not evident that the claimed cells are altered or rendered substantially different from those occurring in nature since the claims only require the insertion of a gene which occurs naturally into the genome of a cell which itself already possesses said gene. Claims like claims 2-3, and 7 which require “increase in the expression” and “high mRNA expression” fail to further distinguish the claimed cells because Francisco et al. teaches that PD-L1 expression is increased in iTreg cells that occur in nature relative to regular Treg cells. Still further, the composition claims (claims 10-16) only require the cells themselves and add no ingredients which would distinguish even the composition from the naturally occurring counterpart.
To be patent eligible, a claimed product must be both non-naturally occurring and markedly different from naturally occurring products. See Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. __, 133 S. Ct. 2107, 2116, 106 USPQ2d 1972 (2013) in which the Court stated:
Groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the §101 inquiry. In Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S. 127 [76 USPQ 280] (1948), this Court considered a composition patent that claimed a mixture of naturally occurring strains of bacteria that helped leguminous plants take nitrogen from the air and fix it in the soil. Id., at 128–129. The ability of the bacteria to fix nitrogen was well known, and farmers commonly “inoculated” their crops with them to improve soil nitrogen levels. But farmers could not use the same inoculant for all crops, both because plants use different bacteria and because certain bacteria inhibit each other. Id., at 129–130. Upon learning that several nitrogen-fixing bacteria did not inhibit each other, however, the patent applicant combined them into a single inoculant and obtained a patent. Id., at 130. The Court held that the composition was not patent eligible because the patent holder did not alter the bacteria in any way. Id., at 132 (“There is no way in which we could call [the bacteria mixture a product of invention] unless we borrowed invention from the discovery of the natural principle itself”). His patent claim thus fell squarely within the law of nature exception. So do Myriad's. Myriad found the location of the BRCA1 and BRCA2 genes, but that discovery, by itself, does not render the BRCA genes “new … composition[s] of matter,” §101, that are patent eligible. Id. 1979.
In this case, even if the claimed cells were necessarily isolated, their isolation would not alter or render the cells markedly different from the cells as they occur in situ. Accordingly, absent a showing of any difference, the claims are herein rejected as encompassing a naturally occurring product, which is not patent eligible.
Claim Rejections - 35 USC § 102
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 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 1-14, and 16 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by WO2020/049535, published: 12 March 2020, hereinafter “Rezania”, provided by Applicant on the IDS submitted on 30 August 2024.
Regarding claim 1, Rezania discloses genetically modified universal donor cells which comprise at least one genetic modification that increases the expression of at least one polynucleotide that encodes a tolerogenic factor (Rezania, Abstract). Rezania specifically teaches to knock in PD-L1 ([000333], Table 1) to the B2M genomic locus of human pluripotent stem cells (Example 4, [000359]). Thus, Rezania discloses the invention of instant claim 1.
Regarding claim 2, the gene sequence is different from unmodified cells insofar as unmodified cells do not have PD-L1 in their B2M locus. Further, the expression of PD-L1 is increased in the knock in cells as evidenced by the ability to select for clones on PD-L1 expression alone ([000360]).
Regarding claim 3, the ability to select knock in cells on their expression of PD-L1 protein alone denotes an increased PD-L1 mRNA expression level insofar as the modified cells must have more PD-L1 mRNA than unmodified cells to be able to have the PD-L1 protein which the unmodified cells do not have.
Regarding claim 4, Rezania knocked PD-L1 into CyT49 cells which are a human embryonic stem cells line (Rezania, [000360]).
Regarding claim 5, the PD-L1 of Rezania was knocked in at the B2M genomic locus.
Regarding claim 6, Rezania discloses the differentiation of the stem cells into pancreatic endoderm cells (Example 8, [000370]).
Regarding claim 7, Rezania discloses the detection of PD-L1 expression in the pancreatic endoderm cells ([000374]).
Regarding claim 8, Rezania discloses pancreatic endoderm cells.
Regarding claim 9, Rezania discloses human embryonic stem cells.
Regarding claim 10, Rezania claims a composition comprising the cells (claim 33).
Regarding claim 11, Rezania claims methods of treating humans having a disease by administering the cells (Claims 34-40) and discloses the same using the composition ([000186]). Thus, Rezania discloses a cell therapeutic composition.
Regarding claim 12, Rezania discloses human embryonic stem cells.
Regarding claim 13, Rezania discloses pancreatic endoderm cells differentiated from human embryonic stem cells.
Regarding claim 14, Rezania explicitly discloses the detection of PD-L1 expression in the pancreatic endoderm cells ([000374]), claims compositions comprising the cells (claim 33), claims methods of treating humans having a disease by administering the cells (Claims 34-40), and discloses the same using the composition ([000186]).
Regarding claim 16, Rezania claims methods of treating humans having a disease by administering the cells (Claims 34-40) and discloses the same using the composition ([000186]). Thus, Rezania discloses a cell therapeutic composition.
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, 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.
Claims 1, 7, and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over WO2020/049535, published: 12 March 2020, hereinafter “Rezania”, provided by Applicant on the IDS submitted on 30 August 2024.
Regarding claim 15, Rezania discloses genetically modified universal donor cells which comprise at least one genetic modification that increases the expression of at least one polynucleotide that encodes a tolerogenic factor (Rezania, Abstract). Rezania specifically teaches to knock in PD-L1 ([000333], Table 1) to the B2M genomic locus of human pluripotent stem cells (Example 4, [000359]). Rezania explicitly discloses the detection of PD-L1 expression in the pancreatic endoderm cells ([000374]), claims compositions comprising the cells (claim 33), claims methods of treating humans having a disease by administering the cells (Claims 34-40), and discloses the same using the composition ([000186])
Rezania does not explicitly disclose the differentiation of the embryonic stem cells with PD-L1 knocked in into any one of the listed cell types in claim 15.
However, Rezania does teach the differentiation of the stem cells into pancreatic endoderm cells ([000370]) and suggests to differentiate the stem cells into a vast array of different cell types including endothelial cells and cardiomyocytes ([000158]).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have differentiated the embryonic stem cells having a PD-L1 gene knocked into their B2M locus of Rezania into at least either cardiomyocytes or endothelial cells and to have arrived at the invention claimed in instant claim 15 with a reasonable expectation of success because Rezania directly suggests to do so. There would have been a reasonable expectation of success insofar as Rezania teaches that the PD-L1 expression is retained upon differentiation and the differentiation of embryonic stem cells into any conceivable somatic cell is understood by a person having ordinary skill in the art as a defining characteristic of those stem cells.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDAN THOMAS TINSLEY whose telephone number is (703)756-5906. The examiner can normally be reached Mon-Fri 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MARIA G LEAVITT can be reached at 571-272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRENDAN THOMAS TINSLEY/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
