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 .
Claim Status
Claims 1 – 20 are pending in this application.
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 15 and 20 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 claims 15 and 20, the phrases "for example", “such as”, and “preferably” render the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 103
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.
Claims 1, 2, 4, 6, 9, 14 and 17 - 19 are rejected under 35 U.S.C. 103 over Takayama et al. (U.S. Patent No 11,359,178 B2) in view of Dyachuk et al. (Parasympathetic neurons originate from nerve-associated peripheral glial progenitors, July 2014, Vol. 345, Issue 6192), hereinafter Takayama and Dyachuk. The references mapped to the prior art are in bold print and parenthesis (), within the claims when present.
Regarding claim 1, Takayama teaches (Takayama, col. 4, lines 25 - 45) a method of making parasympathetic neurons (parasymN) but does not teach comprising culturing of Schwann Cell Progenitors (SCPs) (Dyachuk, Abstract) however, in (a) chemically-defined parasymN differentiation media (Takayama, col. 12, line 59 – col. 13, line 3) is taught.
Regarding claim 2, Takayama teaches the chemically-defined parasymN differentiation media comprising:
FBS (col. 13, line 18)
GDNF (col. 6, lines 31- 32)
BDNF (col. 6, lines 23 – 24)
CNTF (col. 7, lines 51 – 52)
NGF, the lack of NGF is an optional limitation (claim 1, col. 16, lines 10 – 11)
Regarding claim 4, Takayama teaches a method comprising culturing the cells for about two or more weeks (Figure 3 and col. 14, lines 13 – 23; “13 – 87 days”).
Regarding claim 6, Takayama teaches that the progenitors form (col. 12, line 30) (spheroids) cell aggregates, which is an inherent characteristic of culturing stem cells.
Regarding claim 9, Takayama teaches the method of claim 6, where the cells aggregates are cultured on a substrate coated (col. 7, lines 62 – 65) with Polyornithine (PO)/laminin (LM)/fibronectin (FN).
Regarding claim 14, Takayama teaches a method of parasympathetic differentiation, which inherently induces differentiation of about 50% (optimizable quality) of the cells into parasymN.
Regarding claim 17, Takayama teaches a method comprising isolating parasymN from other cells in the culture, optionally wherein the other cells comprise one or more of stem cells and NCC (col. 2, lines 44 – 46; col. 3, lines 8 – 10).
Regarding claim 18, Takayama teaches a method of parasympathetic (col. 4, lines 25 - 45) differentiation to produce a population of cells.
Regarding claim 19, Takayama teaches that the cells from the previous claim are in a medium, therefore creating conditioned media, which is an inherent quality of Takayama’s protocol.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified and/or optimized Takayama to incorporate the teachings of Dyachuk to use the SCPs as their starting point for parasymN differentiation.
Regarding claims 1, 2, 4, 6, 9, 14 and 17 - 19, Takayama teaches all of the elements of the current invention except the use of Schwann cell progenitors. Takayama used Neural crest cells. Dyachuk teaches and provides motivation for the use of Schwann cell precursors (Abstract), not neural crest cells. Dyachuk suggests which cells to differentiate into parasympathetic neurons based off their findings about the parasympathetic system in mice.
Claims 5, 7, 8, 10 – 13 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Takayama and Dyachuk as applied to claims 1, 2, 4, 6, 9 and 17 - 19 above, and further in view of Cho et al. (W.O. Patent Application No. 201835907), hereinafter Cho.
Regarding claim 5, Takayama, Dyachuk, and Cho teach a method where the SCPs (Dyachuk, Abstract, the use of SCPs) are prepared by culturing Neural Crest cells (Takayama, col. 4, lines 25 – 45), Cho teaches a chemically-defined SCP differentiation media (Cho, pg. 16, Example 1).
Regarding claim 7, Takayama teaches all of the elements of the current invention as stated above including, the method of claim 6. Cho teaches the use of SCPs being cultured in SCP differentiation media for about 6-14 days (Cho, Example 1, pg. 16).
Regarding claim 8, Takayama teaches all of the elements of the current invention as stated above except, the SCP differentiation media.
Cho teaches a Schwann cell precursor induction medium comprising (Example 1, pg. 16):
N2
B27
BSA
GlutaMAX
CT 99021
SB431542
NRG1
β-mercaptoethanol
DMEM/F12 (1:1 mix) and Neurobasal medium
FGF2 (Example 6, pg. 21)
Regarding claim 10, Takayama and Cho teach the method of claim 5, wherein the NCC are prepared by culturing stem cells, optionally embryonic stems cells or induced pluripotent stem cells (Takayama, col. 5, lines 10 – 25) (Cho, pg. 19), in a chemically-defined NCC induction media (Takayama, col. 12, lines 40 – 48).
Regarding claim 11, Takayama and Cho teach the method of claim 10, wherein the NCC induction media comprises a transforming growth factor beta (TGFβ)/Activin-Nodal signaling inhibitor and an activator wingless (Wnt) signaling (Takayama, col. 5, lines 40 – 45; SB431542 and CHIR99021 or CT 99021).
Regarding claim 12, Takayama teaches (col. 12, lines 30 – 48) a NCC induction media comprising:
BMP4
SB431542
CHIR99021
Stock solutions for the variation (col. 11, lines 33 – 44)
Regarding claim 13, Takayama teaches the method of claim 12, wherein the NCC are cultured in NCC induction media for 10-12 days (col. 12, lines 30 – 58; steps 1 – 5 takes approximately 10 – 12 days).
Regarding claim 16, Takayama teaches all of the elements of the current invention as stated above except, the method of claim 15, further comprising enriching the parasymN, optionally compromising FACS (Cho, pg. 18) and/or immunopanning.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine and optimize the teachings of Takayama and Cho under the motivation of Dyachuk to produce a protocol for differentiating Schwann progenitor cells into parasymN.
Regarding claims 5, 7, 8, 10 – 13 and 16, Takayama teaches all of the elements of the current invention as stated above except, the use of Schwann cell progenitors. Cho teaches the protocol (pg. 16, Example 1; Figure 1; pg. 32, claim 1) to use for differentiating Schwann cells from stem cells and a chemically-defined SCP medium with the components from claim 8 and the time period of claim 7. Dyachuk (Abstract) provides the motivation and rationale for the use of Schwann cell progenitors in a parasymN differentiation protocol. Cho teaches the use of FACS analysis (pg. 18) for determining SCP derivation. Dyachuk provides the motivation for the use of Schwann cells and it would be prima facie obvious to add a sorting element for enriching the parasymN in Takayama’s protocol to increase the inherent outcome of claim 14.
Claims 15 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Takayama and Dyachuk as applied to claims 1, 2, 4, 6, 9, 14 and 17 - 19 above, and further in view of Kida et al. (U.S. Patent No. 11,186,821 B2) and Wehrwein et al. (Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System, Comprehensive Physiology 6:1239-1278, 2016), hereinafter Kida and Wehrwein.
Regarding claim 15 and 20:
Takayama and Dyachuk teach the method of claim 1.
Takayama teaches that the parasymN are characterized by one or more of a neuron-like cell morphology (Figure 8), the appearance of well-developed neurite bundles (Figure 8), expression of one or more autonomic markers such as PHOX2B, ChAT (col. 3, lines 15), and the reduction in SOX10 (col. 5, lines 56 – 59) expression relative to SCPs and/or SCs.
Dyachuk teaches to look at the expression of ASCL1 (Figure 2).
Kida teaches PRPH (Kida, col. 13, lines 43 – 50) and ChAT relative TH (Figures 5 and 6).
Wehrwein teaches cholinergic muscarinic receptors (MusR), which are functionally activated by bethanechol (BeCh) (Wehrwein, Table 5) and functionally inactivated by atropine (Wehrwein, Table 5).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Takayama, Kida, and Wehrwein under the motivation of Dyachuk to provide a process for characterizing and producing parasymN from Schwann cell progenitors.
Takayama’s protocol has laid the foundation for this application. Kida and Dychauk teach which markers to analyze for parasympathetic neurons; while Wehrwein characterizes and teaches the history of muscarinic receptors in the autonomic nervous system.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Takayama and Dyachuk as applied to claims 1, 2, 4, 6, 9, 14 and 17 - 19 above, and further in view of Gibco’s User Procedural Guide for Neurobasal Medium, hereinafter Gibco.
Regarding claim 3, in which the limitations of claim 1 are contained, Takayama and Dyachuk teach the method.
Gibco teaches a Neurobasal medium comprising:
B27
L-Glutamine
Takayama teaches a chemically-defined parasymN differentiation media comprising:
FBS (col. 13, line 18)
GDNF (col. 6, lines 31- 32)
BDNF (col. 6, lines 23 – 24)
CNTF (col. 7, lines 51 – 52)
ascorbic acid (col. 6, lines 53 – 54)
dbcAMP (col. 6, lines 10 – 16)
Retinoic acid (col. 7, lines 25 – 32)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified and/or optimized Takayama to incorporate the teachings of Dyachuk to use the SCPs as their starting point for parasymN differentiation and to combine the teachings of Gibco to provide a proper medium for the maintenance of mature parasymN produced from the protocol.
Takayama teaches all of the elements of the current invention except the use of SCPs, Neurobasal medium, B27 supplementation, and the use of L-glutamine. B27 is used for long-term survival, maturation, and functional maintenance of mature neurons, often used after initial N2-driven differentiation to support later stages. L-glutamine is a vital nutrient in neuronal cell culture, acting as a primary energy source, a precursor for certain neurotransmitters, and a building block for proteins and nucleotides, crucial for neuronal growth, survival, and function, supporting both metabolic needs and neurotransmission. Dyachuk teaches and provides motivation for the use of Schwann cell precursors (Abstract). Gibco teaches and provides motivation for the use of Neurobasal medium, B27, and L-glutamine as the cells differentiate into mature parasympathetic neurons.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER JACKSON III whose telephone number is (571)272-0247. The examiner can normally be reached Monday - Friday 9:00AM - 5:00PM.
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/WALTER JACKSON III/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638