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 .
Applicant’s election without traverse of Group I, claims 1, 5, 8, 11, 12, 18, 19, 25, 35, 36, 43-47, 57, 71, 76, 90, 94, 115, 122, 126 and 146 in the reply filed on 1/21/2026 is acknowledged.
Claim 3 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/21/2026.
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 122 and 126 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, claims do not recite something significantly different than a judicial exception. The rationale for this determination is explained below.
The Claims
The claims are directed to:
A gonadal cell population that expresses LHX1
Teachings in the Art
Regarding claims 122 and 126, the art teaches that gonadal cells occur naturally and naturally express LHX1 (see Parker et al., Knobil and Neil’s Physiology of Reproduction, Third Ed., Chapter 8, pgs. 313-336, particularly page 319).
Teachings in the Specification
The specification teaches in Example 1-4 the stepwise differentiation of pluripotent stem cells into the claimed gonadal cells. However, the gonadal cells and cell population expressing LHX1 were not subjected to any modification that would markedly distinguish them from their natural occurring counterparts. While the claimed cells were obtained from an in vitro differentiation method, the claimed cells and cell population recite no structural or functional feature that would distinguish them from those that occur in nature.
Accordingly, the claims are directed to a composition using only a nature-based product, i.e., gonadal cells that express LHX1, this nature-based product is then analyzed to determine whether it has markedly different characteristics from any naturally occurring counterpart(s) in their natural state. The claims thus encompass gonadal cells which are identical (no difference in characteristics) to naturally occurring gonadal cells.
Because there is no difference between the gonadal cells used in the claimed composition, the claimed gonadal cells and cell population do not have markedly different characteristics, and thus are a “product of nature” exception. In re Roslin Institute (Edinburgh), 750 F.3d 1333, 1338-39 (Fed. Cir. 2014). Accordingly, the claimed compositions are directed to an exception. Because the claimed compositions do not include any additional features that could add significantly more to the exception, the claimed cardiomyocytes and PSCs do not qualify as eligible subject matter, and should be rejected under 35 U.S.C. § 101.
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An examination of Step 2A in the revised 101 guidance, with respect to the claimed invention, the answer is yes since the claimed compositions comprise only a naturally occurring products (judicial exceptions), in the instant case this naturally occurring products are gonadal cells.
It is only the recited limitations in the claims that are examined under 101 and not aspects such as what the cells are capable of being used for (i.e. for use in transplantation). In this case only gonadal cells or a cell population comprising cells that express LHX1 are examined with respect their status as a judicial exception. It is emphasized that the claimed invention is a composition and not a method.
An examination of Step 2B, the answer is no with respect to the claimed invention. There are no other additional elements recited in the claims that would amount to significantly more than the judicial exceptions. This is because while the claimed invention is drawn to gonadal cells, there are no additional components which impart any additional element or structural limitations to the recited cells. The gonadal cells of the claims are indistinguishable from gonadal cells that exist in nature. The gonadal cells of the claims have the same capability as those that exist in nature and the fact that they are present in an isolated population or produced by a specific method does not change the gonadal cells in significant or meaningful way to amount to more than the judicial exception.
The only factors which can be examined under 101 in the claimed composition are those that are recited in the claim i.e. a gonadal cell and a cell population comprising cells that express LHX1.
How the claimed cells and cell population are obtained and the knowledge of using said cells and population are not considered with respect to a composition, it is only the judicial exceptions themselves that are analyzed under 101 and in this case all of the components in the claimed composition are naturally-occurring products and thus qualify as a judicial exception.
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.
Claim(s) 122 and 126 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sasaki et al. (2015, Cell Stem Cell, Vol. 17, pgs. 178-194).
Claims 122 and 126 are drawn to a product by process; the process of making carries little patentable weight. In the instant case, the process of obtaining a gonadal cell population or a cell population comprising cells that express OSR1 or LHX1 from pluripotent stem cells does not impart any specific property or function to the claimed cell populations that would distinguish them from the prior art. It is only the product, which is anticipated by the prior art and not the process, by which the product was made. This is because the final product, a gonadal cell population or a cell population comprising cells that express OSR1 or LHX1 is not distinguished by any particular features or characteristics resulting from the process by which it is made. Thus the method of making a gonadal cell population or a cell population comprising cells that express OSR1 or LHX1 does not impart any specific property or function to the claimed cell populations. Patentability of a product-by-process claim is determined by the novelty and nonobviousness of the claimed product itself without consideration of the process for making the product.
Regarding claim 122, Sasaki et al. teach a gonadal cell population termed human primordial germ cell-like cells (see Abstract and pg. 183 col. 2 parag. 1).
Regarding claim 126, Sasaki teaches a cell population comprising LHX1 (Figs. 3H and S7E).
Thus the teachings of Sasaki clearly anticipate the invention of claims 122 and 126.
Claim Rejections - 35 USC § 103
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 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(s) 1, 5, 8, 11, 12, 18, 19, 25, 35, 36, 43-46, 57, 71, 76, 90, 94, 115, 126 and 146 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sasaki et al. (2015, Cell Stem Cell, Vol. 17, pgs. 178-194) in view of Lam et al. (2014, J. Am. Soc. Nephrol., Vol. 25, pgs. 1211-1225) and Pui et al. (2017, Mechanisms of Development, Vol. 144, pgs. 125-139) and evidenced by the teachings of Nicol et al. (2018, Human Mol. Genet., Vol. 27(24), pgs. 4273-4287), Warga et al. (2007, Developmental Biology, Vol. 310, pgs. 211-225) and Evseenko et al. (2010, PNAS, Vol. 107(31), pgs. 13742-13747).
Regarding claims 1, 5, 8, 76, 115, 122, 126, Sasaki et al. teach a method of producing a gonadal cell population comprising:
culturing human pluripotent stem cells in a mesoderm induction medium comprising Activin A to produce a population of cells that express Brachyury (aka T),
culturing the cells that express T in an intermediate mesoderm induction medium to produce a population of cells that express LHX1, and
culturing the cells expressing LHX1 in a gonadal induction medium comprising BMP4 to produce a gonadal cell population (see Abstract, pg. 191, Figs. 4 and S1-S7).
Regarding claims 11, 18 and 25, Sasaki teaches using the GSK3 inhibitor CHIR99021 (pg. 181 col. 1 parag. 1).
Regarding claims 12 and 94 and the expression of FOXL2 on gonadal cells, the teachings of Nicol et al. are relied upon in teaching that FOXL2 is a marker of gonadal cells and thus it is interpreted that the gonadal cells of Sasaki inherently express FOXL2.
Regarding claims 19, 43 and 44, Sasaki teaches using the ROCK inhibitor Y-27632 at multiple steps, which can block apoptosis (pg. 191 col. 2 parags. 1 and 2).
Regarding claim 35 and the co-expression of Brachyury, N-Cadherin, EpCam and NCAM, Sasaki teaches the co-expression of EpCam and Brachyury (aka T) on their intermediate mesoderm cells (Figs. 1 and 5). While Sasaki does not teach the additional co-expression of N-Cadherin and NCAM, this would be inherent in view of the teachings of Warga et al. and Evseenko et al. who teach respectively, that N-cadherin and NCAM are expressed on intermediate mesoderm.
Regarding claim 36, Sasaki teaches that at least 90% in the cell population are mesoderm-like cells (Fig. 2).
Regarding claim 57, Sasaki teaches that the culturing time for intermediate mesoderm induction is about 4-14 days (pg. 191 col. 1 parag. 1).
Regarding claim 90, Sasaki teaches that the period of time for culturing in gonadal induction medium is about 5 days to about 21 days (Fig. 2A).
Regarding claim 146, Sasaki teaches culture on fibronectin-coated plates which is a means of adhesion culture (pg. 191 col. 2 parag. 2).
Sasaki does not teach:
Regarding using an RAPM to produce LHX1 expressing cells in claims 1, 45, 46, 71, Lam et al. teach that using retinoic acid in a method of producing LHX1 expressing cells is the most efficient method of producing intermediate mesoderm expressing LHX1 (pg. 1212 col. 2 parag. 1).
Regarding using FGF to produce gonadal cells, Pui et al. teach that BMP can be combined with FGF during differentiation such that BMP signaling is necessary for the formation of primordial germ cells and FGF signaling regulates gonadal sex determination (pg. 128 col. 2 parag. 1).
Thus at the time of filing the ordinary artisan would have found it prima facie obvious to combine the teachings of Sasaki regarding a method of producing a gonadal cell population with the teachings of Lam regarding the benefits of using retinoic acid and Pui regarding the role of FGF in gonadal cell development to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a combination since Lam teaches that retinoic acid is an effective part of producing LHX1 expressing intermediate mesoderm and Pui teaching that BMP and FGF work together to specific primordial germ cells and gonadal cell development.
There would have been a reasonable expectation of success that the retinoic acid of Lam and the FGF of Pui could be used in the method of Sasaki since Lam and Pui both teach that retinoic acid and FGF have a role in obtaining intermediate mesoderm and gonadal cells respectively.
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID A MONTANARI whose telephone number is (571)272-3108. The examiner can normally be reached M-Tr 8-6.
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/DAVID A MONTANARI/Examiner, Art Unit 1632
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