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 .
This case has been transferred to Examiner Constantina Stavrou.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-4 and 11-18, in the reply filed on 11/10/2025 is acknowledged. The traversal is on the ground(s) that the previous office action has not rejected any claim in the present application under 35 U.S.C. § 102 and/or 103 over Cheng and/or Fu. This is not found persuasive because a 35 U.S.C. § 102 and/or 103 rejection is not required to support that the claims lack unity of invention. As stated in the requirement for restriction mailed on 09/10/2025, the claims require a technical feature of an induced multipotent endoderm stem cell. This is technical feature is not considered a special technical feature because Cheng et al (CN111304147A, reference of record) teaches a population of multipotent endoderm stem cells (see claim 1 of Cheng). Additionally, Fu et al (2018, Cell Res., reference of record) teaches a population of induced multipotent endoderm stem cells (see “Results” on pg. 9-10).
The requirement is still deemed proper and is therefore made FINAL.
Claims 5 and 7-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected group, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/10/2025.
Status of the Claims
Claims 1-5 and 7-18 are currently pending.
Claims 4 and 9 are amended.
Claims 5 and 7-10 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claim 6 is cancelled.
New claims 11-18 have been added.
Claims 1-4 and 11-18 have been considered on the merits.
Specification
The use of the terms Matrige® (at least on pg. 6 and 15) and TrypLE™ (at least on pg. 22), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 1-4 and 11-18 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 contains the phrase “inducing differentiation of a human differentiated cell” which is indefinite. It is unclear how a terminally differentiated cell, the claimed “human differentiated cell” is further differentiated into an smEnSC. Claim 1 should be amended to recite “inducing de-differentiation of a human differentiated cell” or “inducing reprogramming of a human differentiated cell”, or similar. Appropriate clarification is required. The dependents of claim 1 are included in the rejection due to dependency on claim 1.
Claim 12 is unclear. Claim 12 recites the limitation “wherein the smEnSC comprises upregulated transcription factors of FOXA1, TBX3, SOX9, CEBPA, and PROX1, which are key transcription factors for early liver development”. However, this limitation is indefinite. It is unclear how the phrase “which are key transcription factors for early liver development” limits the claimed method. The claim is interpreted to require only the upregulation of the listed transcription factors irrespective if the recited factors are key to any early liver development. Appropriate clarification is required.
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 1-4 and 11-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim et al (Journal of Hepatology, 2019), as evidenced by ThermoFisher (Technical document for DMEM/F12).
Regarding claims 1 and 2, Kim teaches a method for de-differentiating a terminally differentiated human cell into an induced multipotent endoderm stem cell (smEnSC) comprising the steps of culturing the differentiated cell in a culture system under a first culture condition including EGF, A83-01, and CHIR99021 (pg. 98, col. 1, last para; and pg. 98, col. 2, para 1). .
Regarding claim 3, Kim teaches that the differentiated cell is an adult cell(pg. 98, col. 2, para 1).
Regarding claim 4, Kim teaches that the adult cell is a primary parenchymal hepatic cell (also known as a hepatocyte) taken from human patient’s liver(pg. 98, col. 2, para 1).
Regarding claims 13-15, Kim teaches that their method further comprises differentiating the smEnSC into an endoderm-derived cell, and wherein the endoderm-derived cell is a parenchymal hepatic cell (pg. 98, col. 2, last para spanning col. 1, para 1 of pg. 99).
Regarding claim 16, Kim teaches wherein the first culture condition comprises a first culture medium (pg. 98, col. 2, para 1).
Regarding claim 17, Kim teaches that the first medium is DMEM/F12 (pg. 98, col. 2, para 1).
Regarding claim 18, Kim teaches that their culture system further comprises an additive selected from ascorbic acid phosphate magnesium, L-glutamine, MTG, and bFGF, as evidenced by ThermoFisher. ThermoFisher teaches that the DMEM/F12 base media employed in Kim contains L-glutamine(see amino acid components list on pg. 1).
Therefore, Kim anticipates the claims.
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.
Claims 1 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (Journal of Hepatology, 2019), as evidenced by ThermoFisher (Technical document for DMEM/F12), in view of Zhang et al (Stem Cell Reports, 2018).
With regards to claim 11, the limitations of the independent claim 1 are taught above.
Regarding claim 11, Kim teaches that the smEnSCs show a homogenous epithelial-like cell morphology (see Fig. 1D), and that the cells are able to be expanded indefinitely in vitro (pg. 101, col. 2, para 1).
Kim does not teach that the smEnSC expresses CDX2 as required by claim 11.
However, Zhang also teaches the method of claim 1 employing a different starting material, in which an iPSC is cultured in a culture system under a first culture condition, wherein the culture system comprises EGF, A83-01 and CHIR99021 to form an smEnSC (Summary/abstract).
Regarding claim 11, Zhang teaches that the smEnSC produced expresses CDX2 (Summary/abstract, pg. 781, col. 2, last para).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of producing smEnSCs as taught by Kim with the similar CDX2+ smEnSCs taught by Zhang to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Zhang also teaches the method of claim 1 employing a different starting material, in which an iPSC is cultured in a culture system under a first culture condition, wherein the culture system comprises EGF, A83-01 and CHIR99021 to form an smEnSC (Summary/abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Kim with Zhang because both produce the smEnSC using nearly identical methods.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 1 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (Journal of Hepatology, 2019), as evidenced by ThermoFisher (Technical document for DMEM/F12), in view of Mizuguchi et al (US20120231490A1).
With regards to claim 12, the limitations of the independent claim 1 are taught above.
Regarding claim 12, Kim teaches that the smEnSCs demonstrate an upregulated SOX9 transcription factor (pg. 99, col. 2, para 3).
Kim does not teach that the smEnSC comprises upregulated transcription factors of FOXA1, TBX3, CEBPA, and PROX1 as required by claim 12.
However, Mizuguchi teaches about genes/transcription factors which are involved in the differentiation of hepatocyte lineage cells.
Regarding claim 12, Mizuguchi teaches that FOXA1, TBX3, CEBPA, and PROX1 are involved in the differentiation of hepatocyte lineage cells ([0083]).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of producing smEnSCs as taught by Kim with the genes/transcription factors involved in hepatocyte lineage differentiation taught by Mizuguchi to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Mizuguchi teaches about genes/transcription factors which are involved in the differentiation of hepatocyte lineage cells ([0083]). One of ordinary skill in the art would have a reasonable expectation of success when combining Kim with Zhang because both concern the differentiation of hepatocyte lineage cells.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/DAVID A MONTANARI/Examiner, Art Unit 1632