DETAILED ACTION
Claims 1-20 from the claim set filed 7/1/2026 are pending. Claims 12-20 are withdrawn for being directed to non-elected groups and claims 9 and 11 are withdrawn for being directed to non-elected species. Thus, claims 1-8 and 10 are being examined on the merits herein.
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 .
Election/Restrictions
Applicants elected with traverse Group I, claims 1-11, drawn to a method of generating a cerebellum-like organoid from human stem cells in the reply filed 7/1/2026. Examiner notes said election was made with traverse. However, because Applicants did not distinctly and specifically point out the supposed errors in the restriction requirement, the group election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicants’ election of claim 8 as the species of the cerebellum-like organoids and claim 10 as the species of human stem cells is acknowledged. Because Applicants did not distinctly and specifically point out the supposed errors in the species requirement, the species election has been treated as an election without traverse (MPEP § 818.01(a)).
Thus, claims 9 and 11-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-8 and 10 will be examined on the merits herein.
Priority
A claim for benefit of a prior-filed application under 35 U.S.C. 119(a)-(f) or under 35
U.S.C. 120, 121, 365(a)-(c), 386 (a) or 386(c) has been made. The effective filing date of the
present application is 4/3/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4/3/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Objection to the Specification
Trade names or marks used in commerce have been noted in this application. An example that is present in the instant application is the term GLUTAMAX. Trade names or marks used in commerce should be accompanied by the generic terminology; furthermore, theses terms should be capitalized (e.g., GLUTAMAX®) wherever they appear 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.
Appropriate correction is appreciated.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-8 and 10 are rejected under 35 U.S.C. 112(b), 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 1 and the term “cerebellum-like” organoid, it is noted said term is a relative term which renders the claim indefinite. The term “cerebellum-like” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree of what a "cerebellum-like" organoid entails, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The claim is considered indefinite because there is a question or doubt as to what elements are required by a “cerebellum-like” organoid. Does said organoid express certain markers or structural characteristics? What properties are necessary to encompass the phrase “cerebellum-like”? Thus, the metes and bounds of the claim cannot be determined and the claim is indefinite.
In further regards to claim 1 and the term “mature, functional” Purkinje cells, it is noted said term is a relative term which renders the claim indefinite. The term “mature, functional” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree of what “mature, functional” Purkinje cells entail, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The claim is considered indefinite because there is a question or doubt as to what elements are required by “mature, functional” Purkinje cells. Do said cells express certain markers or structural characteristics? What properties are necessary to encompass the phrase “mature, functional”? Thus, the metes and bounds of the claim cannot be determined and the claim is indefinite.
Additionally, in regard to claim 1, point d) refers to “the one or more SMAD signaling inhibitors”. There is no previous mention of “the one or more SMAD signaling inhibitors” within claim 1. Rather, claim 1 points a)-c) refer to “the two or more SMAD signaling inhibitors”. Thus, there is insufficient antecedent basis for this limitation in the claim.
Thus, the claim is properly rejected as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Due to each of claims 2-8 and 10 depending directly or indirectly from claim 1, said claims each inherit the deficiencies thereof and thus are rejected on the same basis.
Claim 6 is rejected under 35 U.S.C. 112(b), 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 6 contains the trademark/trade name 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 identify/describe a supplement of a culture medium and accordingly, the identification/description is indefinite.
In further regards to claim 6, Applicant recites the limitation "(L-alanyl-L-glutamine dipeptide)". The use of parentheses around this phrase creates ambiguity regarding the metes and bounds of the claim. It is unclear whether the parenthetical language is intended to be a required limitation of the claim or merely an exemplary or optional feature.
Thus, because the scope of the claim cannot be reasonably ascertained, the claim fails to meet the definiteness requirements of 35 USC 112(b).
Claim Rejections - 35 USC § 112(a)
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.
Claims 1-8 and 10 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 1 is directed to a method of generating a cerebellum-like organoid from human stem cells. Said method, as currently written, requires:
A method of generating a cerebellum-like organoid from human stem cells, comprising:
a. culturing (FOR AN UNSPECIFIED AMOUNT OF TIME) (ANY AMOUNT) of the human stem cells in the presence of (ANY AMOUNT) of two or more SMAD signaling inhibitors, (ANY AMOUNT) of a glycogen synthase kinase 3 (GSK3) inhibitor, and optionally (ANY AMOUNT) of a rho- associated, coiled-coil containing protein kinase (ROCK) inhibitor (ROCKi) in (ANY AMOUNT) of a growth factor-reduced medium to obtain (WITHIN AN UNSPECIFIED AMOUNT OF TIME) neuronal lineage embryoid bodies (EBs);
b. culturing (FOR AN UNSPECIFIED AMOUNT OF TIME) (ANY AMOUNT) of the neuronal lineage EBs derived from step a) in the presence of (ANY AMOUNT) of a midbrain- hindbrain morphogen and (ANY AMOUNT) of the two or more SMAD signaling inhibitors and (ANY AMOUNT) of the GSK3 inhibitor in (ANY AMOUNT) of the growth factor-reduced medium, thereby obtaining (WITHIN AN UNSPECIFIED AMOUNT OF TIME) midbrain-hindbrain regionalized tissues;
c. culturing (FOR AN UNSPECIFIED AMOUNT OF TIME) (ANY AMOUNT) of the midbrain-hindbrain regionalized tissues from step b) in the presence of (ANY AMOUNT) of the midbrain-hindbrain morphogen, (ANY AMOUNT) of the two or more SMAD signaling inhibitors, and (ANY AMOUNT) of the GSK3 inhibitor in a first cerebellar differentiation medium (CerDM1), thereby obtaining (WITHIN AN UNSPECIFIED AMOUNT OF TIME) isthmic organizer regionalized tissues;
d. culturing (FOR AN UNSPECIFIED AMOUNT OF TIME) (ANY AMOUNT) of the isthmic organizer regionalized tissues from step c) in (ANY AMOUNT) of a second cerebellar differentiation medium (CerDM2) in motion, in an agitated environment, or on an orbital shaker, thereby obtaining (WITHIN AN UNSPECIFIED AMOUNT OF TIME) cerebellar neuroepithelial tissues, wherein the CerDM2 does not contain the one or more SMAD signaling inhibitors, the GSK3 inhibitor, the ROCKi, and the midbrain-hindbrain morphogen; and
e. culturing (FOR AN UNSPECIFIED AMOUNT OF TIME) (ANY AMOUNT) of the cerebellar neuroepithelial tissues from step d) in the presence of (ANY AMOUNT) of a thyroid hormone and optionally further in presence of (ANY AMOUNT) of one or more of a solubilized basement membrane matrix, (ANY AMOUNT) of stromal cell-derived factor 1 alpha (SDF 1 a), and (ANY AMOUNT) of brain-derived neurotrophic factor (BDNF) in a third cerebellar differentiation medium (CerDM3) thereby forming (AFTER AN UNSPECIFIED AMOUNT OF TIME) a cerebellum-like organoid,
wherein the cerebellum-like organoids contain mature, functional Purkinje cells.
Dependent claims 2-8 and 10 either depend directly from claim 1 or incorporate the product of claim 1.
To satisfy the written description aspect of 35 U.S.C. 112, first paragraph, Applicants must show that they are in possession of the invention being claimed. Possession of an invention may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings, structural or chemical formulas or sequences that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998).
The application is considered to lack written description for the full genus of the method of claim 1, as currently written.
After reviewing the specification and the prior art, it appears a method of generating a cerebellum-like organoid requires a very exact process with precise timing of agents to be added at specific concentrations. i.e., it is imperative that specific concentrations of agents are added or removed at precise timepoints. Further, as will be appreciated by a POSITA and as is noted by Watson (Watson, et al., The Cerebellum (2018) 17: 419-417; PTO 892), only a handful of studies have generated Purkinje cells from human pluripotent stem cells, with most of these protocols proving challenging to reproduce (Abstract).
Figure 14 provides a clear and precise timeline for the addition and removal of specific agents. Paragraphs [0137]-[0140] provide specific concentrations of the agents to be added to the culture medium.
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However, with regards to the claimed method which as currently written does not require specific concentrations nor a specific timeline, Applicants have not disclosed a representative number of species within the genus to demonstrate Applicants were in possession of the full genus of the method as claimed. The specific concentrations and timeline provided in the specification (Fig 14; [0137]-[0140]) are not representative of the broad genus of the method of generating a cerebellum-like organoid which is encompassed by the claims.
Accordingly, the claims are considered to lack sufficient written description and are properly rejected under 35 USC 112, first paragraph.
Claims 1-8 and 10 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification, while being enabling for a method of generating a cerebellum-like organoid from human stem cells in which precise concentrations of agents are added and removed at precise timepoints, as indicated in Fig 14 and paragraphs [0137]-[0140] of the specification, does not reasonably provide enablement for the genus of the method as currently claimed which does not require specific concentrations nor specific times at which agents are added and removed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with this claim. Dependent claims 2-8 and 10 either depend directly or indirectly from claim 1.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” See MPEP § 2164. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill:
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples;
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Breadth of the claims:
With respect to the breadth of the claims, the claims as currently drafted encompass the genus of a method of generating a cerebellum-like organoid from human stem cells comprising any concentration of agents and cells as well as any period of time for agents to be added and removed. Consequently, the breadth of the claims is expansive.
Nature of the invention:
The invention is in the field of cerebellum organoid development.
The nature of the invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fec. Cir. 2001).
The state of the prior art and predictability in the art:
With respect to the state of the prior art, and predictability of the art, at the time of filing the instant invention, only a handful of studies had generated Purkinje cells from human pluripotent stem cells. For example, Muguruma (Muguruma et al., Cell Reports (2015) 10: 537-550; IDS filed 4/3/2024) disclosed a method to generate the self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells which generated electrophysiologically functional Purkinje cells (Abstract).
However, Watson (Watson, et al., The Cerebellum (2018) 17: 419-417; PTO 892) notes the handful of studies which have generated Purkinje cells from human pluripotent stem cells, comprise protocols which have proved challenging to reproduce (Abstract).
Consequently, there is reason to conclude that there would be a high degree of unpredictability in generating a cerebellum-like organoid from the method of claim 1 as currently written.
Guidance of the Specification/Workinq Examples:
Applicants have not provided working examples encompassing the genus of a method of generating a cerebellum-like organoid as is currently encompassed by claim 1. Applicants have provided a working example for the species of a method of generating a cerebellum-like organoid comprising specific timepoints and concentrations as taught in Fig 14 and paragraphs [0137]-[0140]. The absence of working examples directed to the genus of a method of generating a cerebellum-like organoid claimed, necessitates further experimentation. Therefore, the specification does not provide sufficient guidance on how to make and use the claimed genus of a method of generating a cerebellum-like organoid.
The Quantitation of Experimentation Required:
Undue experimentation would be required to practice the invention as claimed due to the amount of experimentation necessary because of the expansive breadth of the claims, the state of the prior art and its lack of predictability, and the lack of guidance in the form of working examples in the specification.
MPEP §2164.01(a), provides that “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
After applying the Wands factors and analysis to claims 1-8 and 10, in view of the Applicant’s entire disclosure, it is concluded that the practice of the invention as claimed in said claims, would not be enabled by the written disclosure. Therefore, claims 1-8 and 10 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to make the invention commensurate in scope with the claims.
Prior Art Made of Record & Conclusion
No prior art has been applied.
Examiner notes other studies have generated Purkinje Cells from human stem cells. Both Muguruma (Muguruma et al., Cell Reports (2015) 10: 537-550; IDS filed 4/3/2024) and Watson (Watson, et al., The Cerebellum (2018) 17: 419-417; PTO 892) teach methods of generating Purkinje Cells from human stem cells. However, the field of cerebellum organoid development is a new field. In addition to being a new field, it is noted in the prior art that there is high degree of unpredictability/reproducibility within the published prior art. Further, Examiner notes when searching the claimed method, the instant inventors were repeatedly noted as the pioneers of this specific protocol. I.e., while other methods exist for generating the claimed Purkinje Cells, said methods differ from the claimed invention in regards to the agents added to the culture. Due to the unpredictability associated with cerebellum organoid development, one would not have had a reasonable expectation of success in taking the known methods and combining the agents in various manners to arrive at the instant claimed invention.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE R SMALL whose telephone number is (703)756-4783. The examiner can normally be reached Monday - Friday 8:30am-4pm.
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/KATHERINE R SMALL/Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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