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 .
Applicant's amendments to the claims filed on 01-05-2026 have been received and entered. Claims 1-20 are pending in the instant application.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-6, in the reply filed on 01-05-2026 is acknowledged.
Claims 7-20 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01-05-2026.
Claims 1-6 are under consideration.
Priority
This application is a 371 of PCT/CN2021/118183 filed on 09/14/2021 which claim priority from foreign application CHINA 202011002775.4 filed on 09/22/2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 03-22-2023, 05-06-2025, 10-16-2025 are in compliance with the provisions of 37 CPR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Claim Objections
Claims 2, 3, 5 are objected to because of the following informalities:
Claim 1 employ the numbers “(1)” and “(2)” which are in the same category with the numbering of claims. It would be clearer if the steps were identified with letters (e.g., a, b, c etc.) to distinguish with the numbering of the claims.
Claim 2 employs the acronyms for “DMH-1”, “SHH”, “SAG” and “FGF8b”. Each of these terms should be identified by its full name, followed by its acronyms in parenthesis at its recitation in the text of the claims.
Claims 3 and 5 employ the tilde symbol “~” which appears to represent for ranges of numerical values. However, this tilde symbol “~” has not been widely recognized in the arts. It would be remedial to amend to symbol of “-” or “to” in the claims.
Appropriate correction is required.
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 1-6 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 recites “consecutive multiple stages”, claims 2, 3, 4, 5 recite “first stage”, “second stage”, “third stage”, “fourth stage”. It is noted that a stage is a condition or phase, whereas a step is an action or instruction. In the context of stem cell induction and differentiation, stages generally refer to the distinct, biological, or morphological states a cell passes through, while steps refer to the specific, actionable, and sequential protocols or media changes applied by researchers to move cells between those stages. In the instant case, the claims are directed to a process of neural induction of stem cells to become dopaminergic neurons (stage with distinct, biological, or morphological state a cell passes through); therefore, it is unclear what biological, or morphological states the “consecutive multiple stages” are referring to. The claims do not recite distinct, biological, or morphological states in different stages recited in the claims. It appears the claims are reciting sequential steps (consecutive multiple steps); therefore, it would be remedial to amend the term “stage” to “step”.
Claim 1 also include the term “ie.” which render the claims indefinite because it is unclear whether the limitation(s) following the term are part of the claimed invention. See MPEP § 2173.05(d).
Claim 5 recites the terms "preferably" in lines 3 to 6, and claim 6 also recites the term "preferably" in line 2 which is vague and render the claim indefinite because it is unclear whether the phrase after the term "preferably" is intended in the claim or not.
Claims 2-4 are included in the rejection because they directly or indirectly depend from rejected claims. Appropriate correction is required.
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.
Claim 1-6 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.
Claims 1-6 are directed to a method for preparing midbrain substantia nigra dopaminergic neurons, comprising culturing stem cells in a medium containing neural induction agents supplementing components in consecutive multiple stages to accomplish induction and obtaining the stem cell-derived midbrain substantia nigra dopaminergic neurons from the culture.
In analyzing whether the written description requirement is met for the genus claim, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics, specific features and functional attributes that would distinguish different members of the claimed genus. 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. An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). 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., Pfaffv. Wells Elecs., 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).
The claims encompass a genus of stem cells in a medium containing a genus of neural induction agents with any concentration and any incubation time that can result in generation of stem cell-derived midbrain substantia nigra dopaminergic neurons (functional limitation).
1. Not all stem cell can be differentiated into neuron. The specification of the claimed invention only discloses embryonic stem cells or induced pluripotent stem cells. For example, stem cell such as adult hematopoietic stem cells cannot be differentiated into neurons:
Roybon et al (STEM CELLS 2006;24:1594–1604, doi: 10.1634/stemcells.2005-0548) teach “failure of trans-differentiation of adult hematopoietic stem cells into neurons” (Title), and Roybon et al stated that “the present study investigates whether highly purified mouse adult hematopoietic stem cells (HSCs), characterized by lineage marker depletion and expression of the cell surface markers Sca1 and c-Kit (Lin2 Sca11 c-Kit1 [LSK]), can be stimulated to adopt a neuronal fate. When the HSCLSK cells were cultured in vitro in neuronal differentiation medium supplemented with retinoic acid, 50% of the cells expressed the neural progenitor marker nestin and no cells had become postmitotic. Electrophysiological recordings on neuron-like cells showed that these cells were incapable of generating action potentials. When the HSCLSK cells either were grown in vitro together with neural precursor cells or were transplanted into the striatum or cerebellum of wild-type mouse, they either differentiated into Iba1-immunopositive macrophage/microglia or died. In conclusion, we demonstrate that adult HSCLSK cells do not have the capacity to leave the hematopoietic lineage and differentiate into neurons.” (Abstract).
2. High concentration of neural induction agents with extended exposure/incubation time can cause adverse/apoptotic effects for neuronal lineages: For example, Retinoic acid (RA) is a primary neural differentiation agent that cannot be used in high concentrations for extended periods of time due to its dose-dependent toxicity, which can lead to abnormal embryonic development, apoptosis, and cellular damage. While RA is crucial for inducing neuronal differentiation from stem cells, excessive amounts can cause toxic developmental effects:
Wang et al (Neurotoxicology and Teratology Volume 100, November–December 2023, 107291, Doi : 10.1016/j.ntt.2023.107291) teach “toxic effects of exogenous retinoic acid on the neurodevelopment of zebrafish (Danio rerio) embryos” (Title). Wang et al stated that “We used exogenous RA to raise the amount of RA signal in the embryos and looked at the effects of excess RA on embryonic morphological development. Upregulation of the RA signal significantly reduced embryo hatching and increased embryo malformation. To further understand the neurotoxic impact of RA signaling on early neurodevelopment, we measured the expression of neurodevelopmental marker genes and cell death and proliferation markers in zebrafish embryos. Exogenous RA disrupted stem cell (SC) and neuron marker gene expression and exacerbated apoptosis in the embryos. Furthermore, we looked into the links between the transcriptional coactivator RBM14 and RA signaling to better understand the mechanism of RA neurotoxicity. There was a negative interaction between RA signaling and the transcription coactivator RBM14, and the morpholino-induced RBM14 downregulation can partially block the effects of RAR antagonist BMS493-induced RA signaling inhibition on embryonic malformation and cell apoptosis. In conclusion, exogenous RA causes neurodevelopmental toxicity, and RBM14 may be involved in this neurotoxic process.” (Abstract).
3. Not all neural induction agents can be used to differentiate into neuron. Some neural induction agents are primary medium induction factors that induce astrogliogenesis (glial cell formation) while inhibiting or not inducing neuronal differentiation from stem cells. For example, factors that activate the JAK-STAT signaling pathway, essential for the switch from neurogenesis to gliogenesis:
Miller et al (Neuron, Volume 54, Issue 3, 2007, Pages 357-369, ISSN 0896-6273, Doi:10.1016/j.neuron.2007.04.019.) teach “a central role for a neuron-driven cardiotrophin-1-gp130-JAK-STAT pathway in the initiation of gliogenesis: ………neurogenic cortical precursors became gliogenic if placed in a postnatal cortical environment. So, what is the extrinsic cue that induces the gliogenic switch? The answer to this came from two coincident lines of study, both of which implicated cytokines of the IL-6 family. This particular subfamily of cytokines include ciliary neurotrophic factor (CNTF), leukemia inhibitor factor (LIF), and cardiotrophin-1 (CT-1), all of which require and induce heterodimerization of two signal-transducing β subunits, the coreceptors LIFRβ and gp130. These receptors activate a number of signaling cascades, including the JAK-STAT pathway” (Page 359, left column). Miller et al also teach that “during the gliogenic period, when ngn1 levels are low, exposure to BMP2 and gliogenic cytokines causes formation of a Smad:p300/CBP:STAT complex that transactivates gliogenic genes. Under these conditions, BMPs also cause expression of inhibitory HLHs such as Id1 (Nakashima et al., 2001) that can antagonize any neurogenic bHLHs expressed in the same precursors, thereby ensuring that precursors make glia and not neurons” (Figure 2) (Page 360, left column).
PNG
media_image1.png
759
1022
media_image1.png
Greyscale
Therefore, the specification lacks sufficient variety of species to reflect the variance in the genus showing contemplated biological function of any neural induction agents can be used to generate dopaminergic neurons from any stem cell with any concentration and time exposure. The claimed invention as a whole is not adequately described if the claims require essential or critical elements which are not adequately described in the specification and which is not conventional in the art as of applicants effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 UsPQ2d 1641, 1646 (1998).
Overall, what these statements indicate is that the Applicant must provide adequate description of biological function of the recited genus of neural induction agents that can be used to generate dopaminergic neurons from any stem cell with any concentration and time exposure such that the Artisan of skill could determine the desired effect, and conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) and Amgen lnc. v.Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). Thus, it is concluded that the written description requirement is not satisfied for the claimed genus
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 1 is rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Studer et al (Pub. No.: US 2019/0211306 A1, Pub. Date: Jul. 11, 2019).
Regarding to claim 1, Studer et al teach “methods to direct the lineage specific differentiation of hESC and/or hiPSC into floor plate midbrain progenitor cells and then further into large populations of midbrain fate FOXA2+LMXlA+ TH+ dopamine (DA) neurons using novel culture conditions.” (Abstract). Studer et al teach “FIG. 26 shows exemplary grafted human DA neurons derived from pluripotent stem cells have electrophysiological features typical of those seen in mouse substantia nigra pars compacta (SNpc)” ([0143], page 18) (For the preamble).
Studer et al teach method for inducing directed differentiation of cells into a population of floor plate midbrain progenitor cells, comprising, a) providing: i) an embryonic stem cell, an induced nonembryonic pluripotent cell; and ii) first inhibitor is SB431542, second inhibitor is LDN-193189, activator of Sonic hedgehog (SHH) signaling is selected from the group consisting of Sonic hedgehog (SHH) C25II and a purmorphamine, and said third inhibitor is CHIR99021; b) contacting said cell population with first and second inhibitor under conditions capable of resulting in said differentiated population of floor plate midbrain progenitor cells such that said contact with said first and said second inhibitor is within 48 hours of plating cells in vitro: c) further contacting said cells with said activator of Sonic hedgehog (SHH) signaling under conditions for differentiating a population of floor plate midbrain progenitor cells; and d) further contacting said cells with said third inhibitor for differentiating said cell population into a population of floor plate midbrain progenitor cells; and e) contacting said population of floor plate midbrain progenitor cells with neuronal maturation medium for differentiation of floor plate
midbrain progenitor cells into floor plate midbrain dopamine (DA) neurons; f) sorting said floor plate midbrain dopamine (DA) neurons for CD142 expression into a population of cells at least 80% positive for CD142 ([0016], page 4-5) (For step (1) and (2)).
Thus, claim 1 is anticipated by Studer et al.
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 2-6 are rejected under 35 U.S.C. 103 as being unpatentable over Studer et al (Pub. No.: US 2019/0211306 A1, Pub. Date: Jul. 11, 2019) in view of Ericson et al (Pub. No.: US 2023/0233617 A1, Foreign Application Priority Data: May 7, 2020).
The teachings of Studer et al above are incorporated herein in their entirety.
Regarding to claim 2, Studer et al teach many different exposure regimens for cells with different neural induction agents during dopaminergic neuron differentiation to obtain optimal yield of cell types:
Studer et al teach exposure to SHH C25II, Purmorphamine, FGF8 and CHIR99021 were optimized for midbrain floor plate and yield of novel populations of DA neuron (see FIG. 1d). Following floor plate induction, further maturation (days 11-25 or longer than 25 days in culture up to at least 100 days in culture) was carried out in differentiation medium based on Neurobasal/B27 in the presence of DA neuron survival and maturation factors such as AA, BDNF, GDNF, TGFβ and dbcAMP (see full methods for details) ([0176], page 23), and wherein said at least one activator of SHH signaling is selected from the group consisting of SHH proteins, Smoothened agonists (SAGs), and combinations of two or more of the foregoing (e.g., claim 9, page 73).
Studer et al teach contacting the cells with different exposure regimens (exposure to LDN-193189+SB431542="LSB", any of SHH agonists (purmorphamine+ SHH) and FGF8 (S/F8)) for specific amounts of time, i.e. 24 hours, 48 hours, etc. with three primary exemplary culture conditions tested with several variations of these primary conditions in order to determine optimal yield of cell types. Systematic comparisons of the three culture conditions (FIG. 1d) were performed using global temporal gene expression profiling ([0349], page 65 see below).
PNG
media_image2.png
1604
1215
media_image2.png
Greyscale
Thus, it is indicating that adding neural induction agents such as LDN-193189, SB431542, SHH C25II, Purmorphamine, FGF8 and CHIR99021 in different exposure regimens with several variations of conditions for specific amounts of time in different differentiation steps was recognized in the prior art reference to be a result-effective variable. A person of ordinary skill in the art would have been motivated to perform the adding different combinations of neural induction agents in different stages of differentiation processes a plurality of times out of the course of routine optimization, in order to determine optimal yield of cell types for obtaining the stem cell-derived midbrain substantia nigra dopaminergic neurons.
Although Studer et al teach “Dual inhibition of SMAD can be achieved with a variety of compounds including Noggin, SB431542, LDN-193189, Dorsomorphin, or other molecules that block TGFβ, BMP, and Activin/Nodal signaling.” ([0165], Page 22), Studer et al do not specifically teach DMH-1 (Dorsomorphin homologue 1). Ericson et al cure the deficiency.
Ericson et al teach methods for differentiating stem cells into ventral midbrain dopaminergic progenitor cells, and into mesencephalic dopaminergic neurons (Abstract). Ericson et al teach the BMP signaling inhibitor is a canonical BMP signaling inhibitor. Exemplary non-limiting examples of BMP signaling inhibitors include DMH1; DMH2; LDN-193189; LDN-214117; etc. ([0121], page 10)
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Studer et al by using inhibitor of BMP signaling such as DMH-1 as taught by Ericson et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Ericson et al teach that neurons showed significant increase of neurite outgrowth and complexity between day 30-40 of culture ([0192] page 14), and protocols for derivation of mDA neurons (dopamine neurons) from hPSCs have been progressively improved, and have now, after extensive evaluation in pre-clinical grafting experiments, reached the point of clinical trials using allogeneic ESCs or autologous iPSCs as starting material ([0314], page 22). Ericson et al teach that ventral midbrain (vMB) progenitors produced by the methods of this invention can be used to screen for factors (such as small molecule drugs, peptides, and polynucleotides) or environmental conditions (such as culture conditions or manipulation) that promote and/or enhance differentiation and maturation of neurons in culture ([0211], page 15). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Ericson et al were successful in generation of dopamine neuron from pluripotent stem cells with detailed instructions and data.
Regarding to claim 3-4, Studer et al and Ericson et al references teach many different exposure regimens for cells with different neural induction agents and different concentrations during dopaminergic neuron differentiation to optimize the quality and quantity of dopaminergic neuron:
Studer et al teach “SB431542 (10 µM (ranging in concentration from 0.5-50 µM, Tocris, Ellisville, Mich.), SHH C25II (100 ng/ml (ranging in concentration from 10-2000 ng/ml, R&D, Minneapolis, Minn.), …., FGF8 (100 ng/ml (ranging in concentration from 10-500 ng/ml, R&D) and CHIR99021 (CHIR; 3 µM (ranging in concentration from 0.1-10 µM, Stemgent).” ([0177], page 24).
Ericson et al teach that “a preferred embodiment comprises the use of SB431542 and DMH-1 at a concentration of 0.1 µM-250 µM, or more preferable 1-25 µM, or most preferable 5 µM of SB431542 and 2.5 µM of DMH-1” ([0127], page 10) and smoothened agonists (SAGs) such as SAG 1.3 at a concentration of about 300 nM (~0.3 µM) ([0128], page 10).
It is noted that Ericson et al teach exposure of stem cells to TGFβ/Activin-Nodal signaling, BMP signaling (i.e. dual SMAD inhibition), activator of Hedgehog (Hh) signaling (i.e. SAG) for different period of times and combination ([0135]-[0138], page 11), and Ericson et al also stated that “using patterning factors that operate via timed exposure rather than precise concentrations as described here opens up new possibilities for robust specification of defined neuronal subtypes for disease modeling, high-throughput drug development and cell replacement therapies” ([0336], page 26). Thus, similar to the teachings of Studer et al above, adding neural induction agents in different exposure regimens during differentiation process was also recognized in the Ericson et al reference to be a result-effective variable. A person of ordinary skill in the art would have been motivated to perform the adding different combinations of neural induction agents in different stages of differentiation processes with different concentration of neural induction agents a plurality of times out of the course of routine optimization, in order to obtain desired cell type and improve the quantity and quality of the dopaminergic neurons.
Regarding to claim 5, Studer et al and Ericson et al references teach various exposure time in different stages for different neural induction agents regimes during dopaminergic neuron differentiation:
Studer et al teach “Exposure to SHH C25II, Purmorphamine, FGF8 and CHIR99021 were optimized for midbrain floor plate and yield of novel populations of DA neuron (see FIG. 1d). Following floor plate induction, further maturation (days 11-25 or longer than 25 days in culture up to at least 100 days in culture) was carried out in differentiation medium based on Neurobasal/B27 in the presence of DA neuron survival and maturation factors” ([0176], page 23). Studer et al teach three primary exemplary culture conditions tested with variation in exposure time with different neural induction agents ([0349], page 65, see below)
PNG
media_image3.png
595
604
media_image3.png
Greyscale
Additionally, Ericson et al teach “at least about 80% ventral midbrain dopaminergic progenitor cells 7-16 days, such as about 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, or about 15 days after first contacting said cell population with the at least one activator of Retinoic Acid (RA) signaling.” (e.g., claim 5, page 31). The population comprising differentiated mesencephalic dopaminergic neurons is obtainable within about 30-40 days after first contacting the plurality of stem cells with the at least one activator of Retinoic Acid (RA) signaling (e.g., claim 27, page 31), and it takes about 60 days to generate human mDA neurons exhibiting mature electrophysiological characteristics in culture ([0314], page 23).
Thus, exposure time for cells with different neural induction agents during dopaminergic neuron differentiation is recognized in the prior art to be a result-effective variable. A person of ordinary skill in the art would have been motivated to expose the cells with different neural induction agents with different time periods during the process of dopaminergic neuron differentiation out of the course of routine optimization, in order to improve the quantity and quality of the dopaminergic neurons.
Regarding to claim 6, Studer et al teach “The present invention relates to the field of stem cell biology, in particular the linage specific differentiation of pluripotent …., but is not limited to, human embryonic stem cells (hESC) in addition to nonembryonic human induced pluripotent stem cells (hiPSC)” ([0008], page 1).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHOA NHAT TRAN whose telephone number is (571)270-0201. The examiner can normally be reached M-F (9-5).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KHOA NHAT TRAN/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632