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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/16/2026 has been entered.
The Claims and Remarks referred to in this Office Action were filed on 05/18/2026.
Status of Claims
Claims 1-5, 7-15 and 17-20 are pending.
Claim 1 is currently amended.
Claim 21 is currently cancelled.
Claims 1-5 and 7-10 are examined on the merits herein.
Claims 11-15 and 17-20 are withdrawn from consideration as being drawn to inventions nonelected without traverse.
Status of Rejections
The cancellation of claim 21 renders any rejections thereof moot.
The rejection of claims 1-5 and 7-10 under 35 U.S.C. 102(a)(2) as being anticipated by Clarke (US 2023/0062612 A1) is withdrawn in light of the amendments to the last 3 lines of claim 1.
Applicant’s arguments, insofar as they pertain to the new rejections of record, are addressed following the rejections.
Claim Rejections - 35 USC § 112(b)
Claims 1-5 and 7-10 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 recites the limitation “wherein the number of HLA class Ib α-chain and ß2-microglobulin molecules on the cell surface of the hypoimmunogenic human cell is increased compared to cells not comprising the exogenous gene encoding ß2 microglobulin” in the last 3 lines. It is unclear whether “cells not comprising the exogenous gene encoding ß2 microglobulin” refers to cells which satisfy conditions (i) to (v) and (vii) of claim 1 (i.e., cells which only differ from the claimed cell in not comprising the exogenous gene encoding ß2 microglobulin), or to any cells which does not comprise the exogenous gene encoding ß2 microglobulin.
Furthermore, there is insufficient antecedent basis for the limitation "the number of HLA class Ib α-chain and ß2-microglobulin molecules on the cell surface of the hypoimmunogenic human cell" in claim 1.
Claims 2-5 and 7-10 are included in the rejection because they depend from claim 1.
Claim Rejections - 35 USC § 102/103
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)(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) 1-5 and 7-10 are rejected under 35 U.S.C. 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over, Clarke (US 2023/0062612 A1, effective filing date 01/17/2020).
Clark discloses a hypoimmunogenic human stem cell comprising deletions of MHC class I human leukocyte antigens (reads on HLA class I of claim 1), MHC class II human leukocyte antigens (reads on HLA class II of claim 1), and CIITA (claim 4) (para 24-25, 117-118), thereby eliminating surface expression of MHC class I molecules in the cells (para 375) (claim 2). MHC class I, or HLA class I, includes HLA-A, HLA-B, and HLA-C (para 259) (claim 3). Clarke discloses an embodiment of the hypoimmunogenic stem cell, which may be a pluripotent stem cell or a differentiated cell thereof (claim 10), wherein the cell has been modified to conditionally express HLA-E (reads on HLA class Ib), HLA-G (reads on HLA class Ib), PD-L1, PD-L2, and ß2 microglobulin (para 319) (claims 1, 5).
Clarke discloses an embodiment of the hypoimmunogenic cells that comprise a “suicide gene,” or a “safety switch” (para 326) (claim 7). Clarke discloses that the safety switch transgene and hypoimmunity gene is integrated into a safe harbor locus selected from the group consisting of an AAVS1 locus, a CCR5 locus, or a Rosa 26 locus (para 101, 107) (claims 8-9).
Clarke discloses that in some embodiments, the isolated human cell comprises deletion or reduced expression of ß2 microglobulin (para 24, 118), indicating that the deletion or reduced expression of ß2 microglobulin in said cell is optional, and therefore the existence of embodiments in which said cell comprises an endogenous gene encoding ß2 microglobulin that is not deficient in expression (claim 1, (vii)).
Clarke is silent as to whether the number of HLA class Ib α-chain and B2-microglobulin molecules on the cell surface of the hypoimmunogenic human cell is increased compared to cells not comprising the exogenous gene encoding B2 microglobulin (i.e., the limitations recited in the last 3 lines of claim 1). The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not the product of the prior art differs, and if so to what extent, from applicant’s claimed product. The prior art discloses a hypoimmunogenic human cell which is similar to applicant’s claimed cell for these reasons: the cell taught in Clarke satisfies conditions (i) to (vii) of claim 1, as set forth above. Thus, it may be inferred that the cell disclosed in Clarke, which possesses the structural properties of the claimed cell (i.e., limitations (i) to (vii) of claim 1), would also possess the functional properties of the claimed cell (i.e., the limitations recited in the last 3 lines of claim 1). Where an examiner cannot determine whether or not the reference inherently possesses properties which anticipate, or render obvious, the claimed invention a rejection under §§102/103 is appropriate. See MPEP §§ 2112-2112.02.
The cited art taken as a whole demonstrates a reasonable probability that the cell disclosed in Clarke is either identical or sufficiently similar to the claimed cell that whatever differences exist, they are not patentably significant. Therefore, the burden of establishing novelty or unobviousness by objective evidence is shifted to applicants. See MPEP § 2112(v). Clear evidence that the cell of the cited prior art does not possess a critical characteristic that is possessed by the claimed cell would advance prosecution and might permit allowance of claims to applicant’s product. Applicant is requested to specifically point out the support for any amendments made to the disclosure and arguments in response to this Office Action, including the claims. See MPEP §§ 714.02 and 2163.06. Applicant is also requested to refer to pages and line numbers in the as-filed specification. It is noted that other art may be applicable under 35 U.S.C. § 102 or 35 U.S.C. § 103(a) once the aforementioned issue(s) is/are addressed.
Response to Arguments
RE: 35 U.S.C. 102(a)(2) as being anticipated by Clarke (US 2023/0062612 A1)
Applicant argues: Applicant has amended claim 1, upon which claims 2-5 and 7-10 depend, to include "an endogenous gene encoding β2 microglobulin that is not deficient in expression" and that "the number of HLA class Ib α-chain and β2-microglobulin molecules on the cell surface in the hypoimmunogenic human cell is increased compared to cells not having the exogenous gene encoding β2 microglobulin." One characteristic of the present invention is that introducing exogenous B2M into cells containing endogenous B2M increases the number of HLA class Ib α-chains and B2M molecules on the cell surface. This feature is neither disclosed nor suggested by Clarke et al.
Clarke et al. discloses that, in some embodiments, the "decreased or eliminated expression of B2M reduces or eliminates expression of one or more of the following MHC-1 molecules: HLA-A, HLA-B, and HLA-C" (paragraph 0390). Clarke et al. only focuses on decreasing the B2M expression to decrease MHC-1 molecule expression. In contrast, the present invention includes an endogenous B2M encoding gene that is not deficient in expression, as well as the introduction of an exogenous B2M encoding gene. The present invention describes that the HLA class Ib α-chains expressed on the cell surface are increased following the introduction of the additional exogenous B2M encoding gene, which contrasts with the focus of Clarke at al. on decreasing levels of MHC-1 molecules by decreasing B2M expression. In the instances in which B2M expression is mentioned in Clarke et al., Clarke et al. describes reduced or silenced expression of B2M and, as such, does not disclose the introduction of an exogenous B2M encoding gene in the presence of an endogenous B2M encoding gene that is not deficient in expression.
In response: Applicant’s arguments have been fully considered, but are not persuasive. As set forth in the rejection above, Clarke discloses an embodiment of the hypoimmunogenic stem cell, wherein the cell has been modified to conditionally express, among other immunosuppressive factors, ß2 microglobulin (para 319). Furthermore, as set forth in the rejection above, Clarke discloses that in some embodiments, the isolated human cell comprises deletion or reduced expression of ß2 microglobulin (para 24, 118), indicating that the deletion or reduced expression of ß2 microglobulin in said cell is optional. This indicates the existence of embodiment(s) in which said cell comprises an endogenous gene encoding ß2 microglobulin that is not deficient in expression. Thus, the cell taught in in Clarke does satisfy, in addition to other limitations, limitations (vi) and (vii) of claim 1.
Applicant argues that Clarke neither discloses nor suggests that introducing exogenous B2M into cells containing endogenous B2M increases the number of HLA class Ib α-chains and B2M molecules on the cell surface. As set forth above, the rejection over Clarke has been modified to a 102/103 rejection because the examiner cannot determine whether or not the reference inherently possesses properties which anticipate, or render obvious, the claimed invention. In this case, Clarke does disclose a cell that satisfies the structural properties of the hypoimmunogenic human cell of claim 1 (i.e., Clarke discloses a hypoimmunogenic human cell that satisfies limitations (i) to (vii) of claim 1). Although Clarke is silent regarding whether said cell has an increased number of HLA class Ib α-chains and B2M molecules on the cell surface compared to cells not comprising the exogenous gene encoding B2M, it may be inferred that the cell disclosed in Clarke, which possesses the structural properties of the claimed cell (i.e., limitations (i) to (vii) of claim 1), would also possess the functional properties of the claimed cell (i.e., the limitations recited in the last 3 lines of claim 1).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Risa Takenaka whose telephone number is (571)272-0149. The examiner can normally be reached M-F, 12-7 EST.
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/RISA TAKENAKA/Examiner, Art Unit 1632
/KARA D JOHNSON/Primary Examiner, Art Unit 1632
