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 .
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.
Claim Status
Claims 1-36 are currently pending and examined on the merits.
Claim Rejections - 35 USC § 112(b)/2nd paragraph
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 1-36 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.
Claims 1 and 24 contain the limitations “from human stem cells” and “differentiating pluripotent stem cells”. It is unclear if the human stem cells are the same or different from the pluripotent stem cells. For examination purposes, claim 1 is interpreted as “[a] method of producing dopaminergic neurons from human pluripotent stem cells… of a protocol for differentiating the human pluripotent stem cells into the dopaminergic neurons”. Claims 2-23 and 25-32 are included in this rejection based on their dependency on independent claims 1 and 24.
The term “better” in claim 33 is a relative term which renders the claim indefinite. The term “better” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For examination purposes, any improvement in differentiation is considered to read on the claims as presented.
Claim Rejections - 35 USC § 112(a)/1st paragraph
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.
Enablement
Claims 33-36 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 specification, while being enabling for a method of producing dopaminergic cells by adding or increasing a concentration of vitamin A in a neurobasal media at approximately day 20 of a differentiation protocol such that the dopaminergic neurons produce more dopamine than cells produced by different methodologies, does not reasonably provide enablement for producing dopaminergic cells which produce more dopamine by culturing in any neurobasal media. The specification 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.
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.
(A) With respect to the breadth of the claims, the claims as currently drafted encompass a method of producing dopaminergic neurons from naïve state cells by culturing in a neurobasal media, wherein the naïve state stem cells differentiate into dopaminergic cells better than primed state stem cells. The instant claims do not require any particular neurobasal media or additives. Nor do the claims require any comparison steps to determine how or whether the differentiation is “better”. Consequently, the breadth of the claims is expansive.
(B) The invention is in the field of.
(C)-(E) With respect to the state of the prior art, and predictability of the art, differentiation of stem cells into neurons is a developing art. As disclosed in Yi et al., (2024) Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson’s disease. Neural Regeneration Research, 20(11): 3193-3206 (hereinafter Yi), a post-filing reference, reviews methods for producing dopaminergic neurons from pluripotent stem cells (PSCs) (Abstract). Yi explains that the process of neural differentiation of PSCs requires a series of steps to mimic the developmental processes (Overview of neural differentiation form embryonic stem cells and induced pluripotent stem cells). Differentiation protocols have been developed utilizing small molecules and transcription factors (Small molecule induced differentiation, Transcription factors induced differentiation, Table 1). The prior art is silent as to differentiation utilizing a neurobasal media alone without a step-wise small molecule differentiation protocol or genetic engineering. Therefore, differentiation of stem cells into neural cells is an art with some degree of unpredictability.
(F)-(G) The applicants have provided multiple working examples directed to methods for differentiating stem cells into dopaminergic progenitor cells by varying vitamin concentration at approximately day 20 of a differentiation protocol. The applicants have not provided working examples for differentiating stem cells into dopaminergic progenitors by culturing in a neurobasal media alone.
(H) Undue experimentation would be required to practice the invention as claimed due to the amount of experimentation necessary because of the breadth of the claims, the state of the prior art and its predictability, and the limited amount of guidance in the form of varied working examples in the specification.
MPEP §2164.01(a), 4th paragraph, 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).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states that, “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at p. 1005.
After applying the Wands factors and analysis to claims 33-36, in view of the applicant’s entire disclosure, and considering the In re Wright, In re Fisher and Genentech decisions discussed above, it is concluded that the practice of the invention as claimed in claims 33-36 would not be enabled by the written disclosure. Therefore, claims 33-36 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 or use the invention as presently claimed.
Written Description
Claims 33-36 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession 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 or structural chemical formulas 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 Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by “whatever characteristics sufficiently distinguish if). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G. D. Searie & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004). See MPEP § 2163.
The specification as originally filed contains no mention of differentiating either naïve state stem cells or primed state stem cells using a neurobasal media alone. The specification is limited to methods of differentiating using a stepwise protocol requiring multiple additives throughout the differentiation protocol (See e.g., [0083], Fig. 1). Therefore, it is not clear that applicants had possession of the full scope of invention as presently claimed.
Claim Rejections - 35 USC § 102
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) 33 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Studer et al., US Publication No. 2018/0094242 (cited on IDS dated 10/30/24, hereinafter Studer).
Regarding claim 33, Studer discloses methods of inducing differentiation of human stem cells into midbrain dopaminergic neurons (Abstract). The human stem cells to be differentiated may be selected from embryonic stem cells (i.e., naïve stem cells), induced pluripotent stem cells, parthenogenetic stem cells, primordial germ cell-like pluripotent stem cells, epiblast stem cells, or F-class pluripotent stem cells ([0019]). Suitable media for the differentiation protocol include Neurobasal media ([0096], [0153]-[0198], [0207]-[0505]).
Therefore, every limitation of claim 33 is present in Studer and the subject matter is anticipated.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27, 31-37 of U.S. Patent No. 1,2104,170. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are all directed to a method of producing dopaminergic neurons from human stem cells comprising a step of adding or increasing a concentration of vitamins to neurobasal media at approximately Day 20 +/−3 of a protocol for differentiating pluripotent stem cells into dopaminergic neurons, wherein the vitamins comprise vitamin A, and wherein the dopaminergic neurons are characterized by producing greater than 30% more dopamine and its metabolites on Day 30 than dopaminergic neurons produced by the same differentiation protocol without added or increased vitamins. The narrower scope of the ‘170 patent anticipates the broader claims of the present invention.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA D JOHNSON whose telephone number is (571)270-1414. The examiner can normally be reached Monday-Friday 8:00-4:00 CT.
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/KARA D JOHNSON/Primary Examiner, Art Unit 1632
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