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 .
Priority
The instant application is a national stage entry under 35 USC 371 of PCT/CN2020/123227, filed
23 October 2020. Acknowledgement is made of Applicants’ claim for foreign priority under 35 USC 119(b) to People’s Republic of China Application No. CN202011097347.4, filed 14 October 2020. Receipt is acknowledged of certified copies of papers, in a non-English language, required by 37 CFR 1.55. Therefore, the earliest possible priority date is 14 October 2020.
Election/Restrictions
Applicants’ election of Group II, encompassing claims 23-27, 30, and 33, in the reply filed on 05 November 2025 is acknowledged. The requirement is still deemed proper and is therefore made FINAL. However, because Applicants did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Accordingly, claims 20-22, 28-29, 31-32, and 34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Therefore, claims 20-34, of record 14 April 2023, are pending. Claims 20-22, 28-29, 31-32, and 34 are withdrawn for reading on the non-elected inventions. Prosecution on the merits comments for claims 23-27, 30, and 33.
Claim Interpretation
Instant claim 33 is directed to neurons that are obtained by the method according to claim 23. This is a product-by-process limitation. Product-by-process limitations are considered only in so far as the method of production affects the structure of the final product. In the instant case, there is no evidence that the production method of claim 23 imparts any particular structure or significance to the neurons. Thus, the claim will be interpreted as if neurons derived from any source or production method fulfills the recited claim limitation. See MPEP § 2113.
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 23-27, 30, and 33 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.
Regarding claim 23: Instant claim 23 recites the terms “preferably” and “further preferably”. In the instant case, the term “preferably” is being treated as exemplary language. Therefore, the exemplary term “preferably” renders the instant claim indefinite because it is unclear whether the limitations following the term are part of the claimed invention. See MPEP § 2173.05(d). For the sake of compact prosecution, the instant claim is interpreted as if the ”preferable” and/or “further preferable” language is not required.
In addition, the instant claim recites a list of preferable limitations without providing a conjunction to define the list as inclusive or exclusive. Therefore, the metes and bounds of the claim cannot be determined, rendering the claim indefinite. For purposes of compact prosecution, the instant claim is interpreted as if there is an “or” between the limitations.
Instant claims 24-27, 30, and 33 are either dependent upon parent claim 23 or fully incorporate the limitations of parent claim 23, and are thus rendered indefinite for the same reasons.
Appropriate correction is required.
Regarding claim 24: The instant claim recites the term “preferably”. In the instant case, the term “preferably” is being treated as exemplary language. Therefore, the exemplary term “preferably” renders the instant claim indefinite because it is unclear whether the limitations following the term are part of the claimed invention. See MPEP § 2173.05(d). For the sake of compact prosecution, the instant claim is interpreted as if the ”preferable” language is not required.
Appropriate correction is required.
Regarding claim 25: The instant claim recites the term “preferably”. In the instant case, the term “preferably” is being treated as exemplary language. Therefore, the exemplary term “preferably” renders the instant claim indefinite because it is unclear whether the limitations following the term are part of the claimed invention. See MPEP § 2173.05(d). For the sake of compact prosecution, the instant claim is interpreted as if the ”preferable” language is not required.
In addition, the instant claim contains the trademarks/trade names “Neurobasal™” and “Glutamax™”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to respectively identify/describe a cell culture medium and cell culture medium supplement and, accordingly, the identification/description of each is indefinite.
Appropriate correction is required.
Regarding claim 26: The instant claim recites the term “preferably”. In the instant case, the term “preferably” is being treated as exemplary language. Therefore, the exemplary term “preferably” renders the instant claim indefinite because it is unclear whether the limitations following the term are part of the claimed invention. See MPEP § 2173.05(d). For the sake of compact prosecution, the instant claim is interpreted as if the ”preferable” language is not required.
In addition, the instant claim recites a list of preferable limitations without providing a conjunction to define the list as inclusive or exclusive. Therefore, the metes and bounds of the claim cannot be determined, rendering the claim indefinite. For purposes of compact prosecution, the instant claim is interpreted as if there is an “or” between the limitations.
The instant claim also contains the trademarks/trade names “Neurobasal™” and “Glutamax™”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to respectively identify/describe a cell culture medium and cell culture medium supplement and, accordingly, the identification/description of each is indefinite.
Appropriate correction is required.
Regarding claim 30: The instant claim recites the term “preferably”. In the instant case, the term “preferably” is being treated as exemplary language. Therefore, the exemplary term “preferably” renders the instant claim indefinite because it is unclear whether the limitations following the term are part of the claimed invention. See MPEP § 2173.05(d). For the sake of compact prosecution, the instant claim is interpreted as if the ”preferable” language is not required.
Appropriate correction is required.
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.
Claim 33 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a nature-based product without significantly more.
Claim 33 is directed to a population of neurons obtained by the method of claim 23. Instant claim 33 comprises a product-by-process limitation, as can be observed in the Claim Interpretation section above and is incorporated in its entirety herein.
The test for 101 eligibility of judicial exceptions can be found at MPEP § 2106:
“First, the claimed invention must be to one of the four statutory categories. 35 U.S.C. 101 defines the four categories of invention that Congress deemed to be the appropriate subject matter of a patent: processes, machines, manufactures and compositions of matter.”
“Second, the claimed invention also must qualify as patent-eligible subject matter, i.e., the claim must not be directed to a judicial exception unless the claim as a whole includes additional limitations amounting to significantly more than the exception. The judicial exceptions (also called "judicially recognized exceptions" or simply "exceptions") are subject matter that the courts have found to be outside of, or exceptions to, the four statutory categories of invention, and are limited to abstract ideas, laws of nature and natural phenomena (including products of nature). Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 216, 110 USPQ2d 1976, 1980 (2014) (citing Ass'n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 589, 106 USPQ2d 1972, 1979 (2013).”
“The Supreme Court in Mayo laid out a framework for determining whether an applicant is seeking to patent a judicial exception itself, or a patent-eligible application of the judicial exception. See Alice Corp., 573 U.S. at 217-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. 66, 101 USPQ2d 1961). This framework, which is referred to as the Mayo test or the Alice/Mayo test, is discussed in further detail in subsection III, below. The first part of the Mayo test is to determine whether the claims are directed to an abstract idea, a law of nature or a natural phenomenon (i.e., a judicial exception). Id. If the claims are directed to a judicial exception, the second part of the Mayo test is to determine whether the claim recites additional elements that amount to significantly more than the judicial exception. Id. citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966). The Supreme Court has described the second part of the test as the "search for an 'inventive concept'". Alice Corp., 573 U.S. at 217-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966).”
Examiners should determine whether a claim satisfies the criteria for subject matter eligibility by evaluating the following steps outlined in a flow chart at MPEP 2106(III) and 2106.04(II)(A):
Step 1: is the Claim to a process, machine, manufacture or composition of matter? If Yes, proceed to Step 2A;
Step 2A, prong one: Is the Claim directed to a law of nature, a natural phenomenon (product of nature), or an abstract idea? If Yes, proceed to Step 2A, prong two;
Step 2A, prong two: Does the claim recite additional elements that integrate the judicial exception into a practical application? If No, proceed to Step 2B;
Step 2B: Does the claim recite additional elements that amount to significantly more (an inventive concept) than the judicial exception? If No, the claim is not eligible subject matter under 35 USC 101.
With regard to Step 1: YES, the claims are each directed to a composition of matter, or product.
With regard to Step 2A, prong one: YES, the claim is directed to neurons, which are nature-based products. More specifically, since the instantly claimed neurons comprise a product-by-process limitation – see Claim Interpretation section above – the claimed neurons are compared to the closest naturally occurring counterpart, which are neurons, per se. Thus, there is no marked different between the claim and product of nature. See, for example, Pages 6-7 of Zhou et al (WO 2018/157769 A1, of record on IDS filed 01 July 2024).
With regard to Step 2A, prong two: No, the claims do not include any additional elements that integrate the judicial exceptions into a practical application. Integration into a practical application requires additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that the claim is more than a drafting effort designed to monopolize the exception.
The claims do not modify or transform the naturally occurring neurons, nor apply the neurons for a particular treatment or medical condition, nor imposes a meaningful limit on the neurons recited therein.
With regard to Step 2B: No, the claim does not provide any additional elements that amount to significantly more (an inventive concept) than the judicial exception.
Taken together, the claim encompasses a natural product. The judicial exceptions are not integrated into practical applications as iterated above. The claim does not include additional elements
that are sufficient to amount to significantly more than the judicial exception as iterated above.
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.
Claim 33 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhou et al (WO 2018/157769 A1, of record on IDS filed 01 July 2024).
Zhou et al disclose methods for transdifferentiating non-neuronal cells into neurons, wherein the non-neuronal cells are cultured in an induction medium comprising a myosin inhibitor, and a maturation medium (Abstract; Pages 1-2, 5-6, 10-13, 18-19; Figure 1).
Accordingly, Zhou et al anticipate the claim as follows:
Regarding claim 33: Instant claim 33 comprises product-by-process. The effect of the product-by-process language is discussed above – see Claim Interpretation – and is incorporated herein in its entirety.
Accordingly, Zhou et al disclose the generation of neurons from non-neuronal cell. This therefore reads on the neurons of the instant claim.
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.
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 23-25, 27, 30, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al (WO 2018/157769 A1, of record on IDS filed 01 July 2024) in view of Li et al (Cell Stem Cell, 2015, of record on IDS filed 14 April 2023).
Zhou et al and Li et al are both considered prior art under 35 USC 102(a)(1). Zhou et al anticipate instant claim 33 based on the Claim Interpretation section above. However, the following rejection relies on an alternative interpretation wherein the production method of instant claim 23 does impose significant structural or functional characteristics to the generated neurons.
Regarding claims 23 and 33: Zhou et al disclose methods for transdifferentiating non-neuronal cells into neurons, wherein the non-neuronal cells are cultured in an induction medium comprising a myosin inhibitor, and a maturation medium (Abstract; Pages 1-2, 5-6, 10-13, 18-19; Figure 1).
Zhou et al do not disclose that the method further comprises treating the non-neuronal cells with an isoxazole compound, as required by instant claim 23.
Li et al, however, disclose that isoxazole 9 (ISX9) is a neuronal-fate-inducing small molecule that is necessary to activate neuron-specific genes during the differentiation of non-neuronal cells to neurons (Abstract; Pages 195-196, 200-201; Figure 4).
Therefore, it would have been prima facie obvious to have modified the method of Zhou et al such that the non-neuronal cells are further contacted with ISX9, as detailed in Li et al. One of ordinary skill in the art would have been motivated to contact the non-neuronal cells with ISX9 in combination with a myosin inhibitor, as they are both small molecules that are necessary to drive the differentiation of non-neuronal cells to neurons (Zhou et al: Pages 1-2; Li et al: Page 200), and would have had a reasonable expectation of success given that the disclosures of Zhou et al and Li et al are both concerned with the generation of neurons from non-neuronal cells. See MPEP § 2143(I)(A) and MPEP § 2143(I)(G).
Consequently, Zhou et al as modified by Li et al render obvious a method of differentiating non-neuronal cells into neurons, wherein the non-neuronal cells are contacted with a myosin inhibitor and ISX9. This therefore renders obvious the method of instant claim 23, and generated neurons thereof of instant claim 33.
Regarding claims 24-25: Following the discussion of claim 23, Zhou et al further disclose that the non-neuronal cells are cultured in an induction medium comprising a myosin inhibitor (claim 25) for 7 days, and a maturation medium for 14 days (Pages 2, 6, 11, 13, 18; Figure 1). This therefore reads on the method of instant claim 24. See MPEP § 2131.03.
Regarding claim 27: Following the discussion of claim 23, Zhou et al further disclose that the non-neuronal cells are fibroblasts (Pages 2, 11, 13; Figure 1). This therefore reads on the method of the instant claim.
Regarding claim 30: Following the discussion of claim 23, Zhou et al further disclose that the methods can be performed in vivo (Page 6). Therefore, the ordinary artisan would recognize that the myosin inhibitor and ISX9 can be administered to a subject in an effective amount to induce the differentiation of non-neuronal cells to neurons within the subject, and would have had a reasonable expectation of success given that it is within the skillset of the ordinary artisan to scale the in vitro concentrations of the small molecules to in vivo concentrations. See MPEP § 2143(I)(G). This therefore renders obvious the method of the instant claim.
Claims 23-27, 30, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al (WO 2018/157769 A1, of record on IDS filed 01 July 2024) in view of Li et al (Cell Stem Cell, 2015, of record on IDS filed 14 April 2023), and further in view of Kollins et al (Dev Neurobiol, 2009).
The discussion of Zhou et al as modified by Li et al regarding claim 23 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Zhou et al anticipate claim 33. Zhou et al as modified by Li et al render obvious claims 23-25, 27, 30, and 33. Kollins et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 26: Following the discussion of claim 23, Zhou et al further disclose that the maturation medium comprises N2 culture additive, B27 culture additive, glutamine, β-mercaptoethanol, NT3, BDNF, GDNF, and db-cAMP (Pages 2-3, 9, 18).
With that, Li et al further disclose that ISX9 is essential in inducing master neural genes, and that the neural-fate of cells is dependent upon ISX9 (Pages 200-201; Figure 4).
The combination of Zhou et al and Li et al fail to teach that the maturation medium comprises a myosin inhibitor and isoxazole compound, as required by instant claim 26.
Kollins et al, however, disclose that the inhibition of myosin-II via blebbistatin allows for neurons to shift towards a mature morphological state (Pages 10; Figure 8).
Therefore, it would have been prima facie obvious to have modified the method of Zhou et al in view of Li et al such that the maturation medium comprises a myosin inhibitor and ISX9, as suggested within Li et al and Kollins et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to include small molecules that are known to impact the maturation of neurons within the maturation medium, and would have had a reasonable expectation of success given the protocols outlined within the disclosure of Zhou et al coupled with the small molecule concentrations provided within the disclosures of Li et al and Kollins et al. See MPEP § 2143(I)(G).
Consequently, Zhou et al as modified by Li et al and Kollins et al render obvious a method of differentiating non-neuronal cells into neurons, wherein the maturation medium comprises a myosin inhibitor and ISX9. This therefore reads on the method of the instant claim.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633