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 .
Status of the Claims
Claims 1-12 are currently pending.
Claims 1-4 are amended.
Claims 5-12 have been added.
Claims 1-12 have been considered on the merits.
Withdrawn Rejections
The rejections made onto claims 3-4 under 35 U.S.C. § 112(b) are withdrawn in light of the amendments submitted on 09/26/2025.
New and Maintained Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
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 3-6 and 9 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.
Claim 3 recites a step/a limitation of “stem cells destined for differentiation into neurons are induced pluripotent stem (iPS) cells that are derived from a healthy subject, patient having a neural disorder, or that have been subjected to gene editing so as to have genes that either cause, or are rink factors for, a neural disorder”. The specification describes employing mature neurons in the methods at paragraph [0071] and [0078]. The specification describes the neurons to be iPSC-derived neurons, however these cells were purchased and used in the method after they had been derived from iPSCs. Therefore, the concept of performing the method using induced pluripotent stem (iPS) cells that are derived from a healthy subject, patient having a neural disorder, or that have been subjected to gene editing so as to have genes that either cause, or are rink factors for, a neural disorder lacks written description.
This is a new matter rejection.
Claim 4 recites a step/a limitation of “wherein the stem cells destined for differentiation into neurons are pluripotent stem cells that have undergone a differentiation induction treatment to form neural cells”. The specification describes employing mature neurons in the methods at paragraph [0071] and [0078]. The specification describes the neurons to be iPSC-derived neurons, however these cells were purchased and used in the method after they had been derived from iPSCs. Therefore, the concept of performing the method using induced pluripotent stem (iPS) cells that have undergone a differentiation induction treatment to form neural cells lacks written description.
This is a new matter rejection.
Claim 5 recites a step/a limitation of “wherein the stem cells destined for differentiation into neurons are stem cells that have been induced to differentiate into neurons by introducing a transcription factor”. The specification describes employing mature neurons in the methods at paragraph [0071] and [0078]. The specification describes the neurons to be iPSC-derived neurons, however these cells were purchased and used in the method after they had been derived from iPSCs. Therefore, the concept of performing the method using stem cells that have been induced to differentiate into neurons by introducing a transcription factor lacks written description.
This is a new matter rejection.
Claim 6 recites a step/a limitation of “wherein the stem cells destined for differentiation into astrocytes are stem cells that have been induced to differentiate into astrocytes by introducing a transcription factor”. The specification describes employing mature neurons in the methods at paragraph [0071] and [0078]. The specification describes the astrocytes to be iPSC-derived astrocytes, however these cells were purchased and used in the method after they had been derived from iPSCs. Therefore, the concept of performing the method using stem cells that have been induced to differentiate into astrocytes by introducing a transcription factor lacks written description.
This is a new matter rejection.
Claim 9 recites a step/a limitation of “wherein said spheroid has a % variation in a calcium transient assay of less than 10%”. The specification teaches a lowest % variation for a 1:1 ratio of neurons : astrocytes to be 13.4%. Nowhere in the specification is a % variation lower than 13.4 obtained for any ratio of neurons to astrocytes. Therefore, the concept of a % variation less than 10% lacks written description.
This is a new matter rejection.
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 1-12 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 phrases “neurons or stem cells destined for differentiation into neurons” and “astrocytes or stem cells destined for differentiation into astrocytes” which renders the claim indefinite. It is unclear whether the phrase is to be read as having to choose from “neurons” or “stem cells destined for differentiation into neurons” or if the phrase is meant to be read as “neurons destined for differentiation into neurons” or “stem cells destined for differentiation into neurons”. It is equally unclear whether the phrase is to be read as having to choose from “astrocytes” or “stem cells destined for differentiation into astrocytes” or if the phrase is meant to be read as “astrocytes destined for differentiation into neurons” or “stem cells destined for differentiation into astrocytes”. Appropriate clarification is required.
Dependent claims 2-12 are included in this rejection.
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 1-2 and 4-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Carromeu et al (US20190017097A1).
Regarding claim 1, Carromeu teaches a method of producing a neural cell-containing spheroid comprising mixing neural cells and astrocytes by having a mixed population of neurons and astrocytes in wells of a well plate that form a spheroid ([0018]). The cells can be present in the well to form the spheroid at a range of ratio, but notably the ratio can be 50/50 as required by claim 1 ([0020]). Carromeu teaches that the spheroids are cultured between 4-16 weeks as required by claim 1, 10, 11, and 12 ([0007]). Carromeu also teaches that the mixture of cells is cultured to form spheroids as required by claim 2 ([0028]). Carromeu teaches that the neural cells and astrocytes are cells which have been differentiated from any human iPSCs as required by claims 1 and 4 ([0027]/[0033]).
Claims 7-9 contain a wherein clause that recites the intended result of the method rather than requiring an additional step be performed. Claim 7 recites an intended result of the method of producing a neural cell-containing spheroid wherein the spheroid has a % variation in a calcium transient assay of less than 20%. Claim 8 recites an intended result of the method of producing a neural cell-containing spheroid wherein the spheroid has a % variation in a calcium transient assay of less than 15%. Claim 9 recites an intended result of the method of producing a neural cell-containing spheroid wherein the spheroid has a % variation in a calcium transient assay of less than 10%. MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that a such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore since these claims only recite the results of the steps, then art reading on claim 1 will also read on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary including unexpected results.
Claims 5 and 6 contain product by process limitations in which the process of deriving neurons or astrocytes from stem cells by introducing a transcription factor carries little patentable weight. It is only the product of the spheroid containing mature neurons and astrocytes, which is anticipated by the prior art and not the process by which the neurons and astrocytes of the product were made. This is because the final product (spheroid of neurons and astrocytes) is not distinguished by any particular features or characteristics resulting from the process by which the neurons or astrocytes were made. As such, the limitations of the claimed process of deriving neurons and astrocytes from stem cells using a transcription factor are met by any mature neurons or astrocytes in the prior art. 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 it which are encompassed by the claimed process deriving the mature neurons and astrocytes of the spheroid from stem cells using a transcription factor of claims 5 and 6. Thus, the teachings of Carromeu anticipate the limitations of claims 5 and 6.
Therefore, Carromeu 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.
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 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Carromeu et al (US20190017097A1), in view of Choi et al (“A three-dimensional human neural cell culture model of Alzheimer’s disease”, Nature Letter, 2014).
With regards to claim 3, the limitations of the independent claim 1 have been taught above.
Although Carromeu teaches the use of human iPSCs in the formation of the spheroids, Carromeu does not teach that the iPSCs are derived from a patient having a neural disorder or that have been subjected to gene editing so as to have genes that either cause, or are risk factors for, a neural disorder as required by claim 3.
However, Choi teaches a method of making 3-dimensional human neural cell culture model of Alzheimer’s disease through the generation of human neural progenitor cells which contain multiple FAD (familial Alzheimer’s disease) mutations, which causes the Alzheimer’s neural disorder hallmarks in the cells (abstract). Choi teaches that their Alzheimer’s model provides a “unique strategy for recapitulating Alzheimer’s disease pathology in the 3D human neural cell culture model may also serve to facilitate the development of more precise human cellular models of other neurodegenerative disorders” (pg. 278, col 1, para 2).
One of ordinary skill in the art prior to the effective filling date of the instant application would find it obvious at the effective filling date of the instant invention to combine the 3D spheroid neural cell spheroid model of Carromeu with the diseased cell mutations of neural cells to model neural disease taught by Choi to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Choi teaches that their Alzheimer’s model provides a “unique strategy for recapitulating Alzheimer’s disease pathology in the 3D human neural cell culture model may also serve to facilitate the development of more precise human cellular models of other neurodegenerative disorders” (pg. 278, col 1, para 2). One of ordinary skill in the art would have a reasonable expectation of success when combining Carromeu with Choi because both provide methods of making 3D neural cell models from both healthy and diseased/gene edited neurons.
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.
Response to Arguments
Applicant's arguments filed 09/26/2025 have been fully considered but they are not persuasive.
Applicant argues (Remarks, pg. 6-7) that the newly added limitation to claim 1 of culturing the spheroid for at least four weeks is not taught by Carromeu and that “there is no disclosure or suggestion of culturing for at least four weeks.
This argument is not found persuasive. Carromeu teaches that the spheroids are cultured between 4-16 weeks ([0007]). Therefore, the argument is not found persuasive.
Applicant argues (Remarks, pg. 7) that Choi et al does not remedy the alleged deficiencies of Carromeu which have been addressed ay point 19 above. Therefore, the argument is not found persuasive.
Conclusion
No claims are 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Examiner Contact Information
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632