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 – 15 are pending in the instant 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 2, 5, 6, 7, 11, 12, 13 and 15 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 6, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 2, 5, 6, 7, 11, 13 and 15, the phrases "in particular" or “more in particular” render the claim(s) indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by "or the like"), thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(d).
Claims 2 and 12 contain the trademark/trade names STEMdiff, Matrigel, and Geltrex. 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 1) a culture medium for stem cells and 2) extracellular basement matrix gel and, accordingly, the identification/description is indefinite.
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 – 11 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Martins et al. (Self-Organizing 3D Human Trunk Neuromuscular Organoids Cell Stem Cell, 2020; 26, 172-186.e6; hereinafter Martins) in view of Kamm et al. (U.S. Patent Application Publication No. 2017/0355945 A1, hereinafter Kamm).
Regarding claims 1 – 2, 12 and 14, Martins discloses a method for obtaining a self-organizing 3D human trunk neuromuscular organoid that fits the criteria of instant claims 1 and 2 (p. e3, In vitro generation of NMPs from HPSCs; Generation of neuromuscular organoids in 3D). Martins refers to resuspending and seeding neuromesoderm progenitors, which is interpreted as representing step d. Martins teaches all of the elements of the current invention as stated above except transferring the neuromuscular 3D organoid to a recipient with a low-binding surface comprising a basement membrane matrix. Martins keeps the organoids in a low-binding surface with no basement membrane matrix, but with specific growth factors. Kamm discloses an invention related to microfluidic devices for the 3D coculture of neuronal and muscle cells, the use of Matrigel (para. [0027]).
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 modify Martins’ protocol with a basement membrane matrix of Kamm. The use of basement membrane matrices is a well-known technique in the art for differentiating and growing organoids.
Regarding claim 3, Martins discloses the use of a GSK-3 inhibitor and basic FGF (p. e3, Generation of neuromuscular…).
Regarding claim 4, Martins discloses the use of ultra-low binding 96-well plates (p. e3, Generation of neuromuscular…).
Regarding claim 5, Martins discloses centrifuging the plates for 2 min at 350 G (p. e3, Generation of neuromuscular…) instead of 100 G.
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 modify Martins’ protocol by reducing the centripetal force in order to minimize shear stress, prevent cell damage, and preserve sample integrity.
Regarding claim 6, Martins discloses that during the whole period, organoids were maintained on an orbital shaker rotating at 75 rpm (p. e3, Generation of neuromuscular…).
Regarding claim 7, Martins discloses the use of accutase for dissociating HPSCs (p. e3, Generation of neuromuscular…).
Regarding claims 8 – 10, Martins discloses resuspending the neuromesodermal progenitors at 4,500 – 9,000/well and a timeline of “re-plating” that fits the range of instant claim 9 (p . e3, Generation of neuromuscular…). Martins does not explicitly disclose a cell density of 22 spheres per well.
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 modify Martins’ cell density and cell culture plates for use in generating neuromuscular organoids. Doing so would adjust an optimizable quality of the organoid that improves differentiation.
Regarding claim 11, Kamm discloses the use of high glucose DMEM (para. [0182]) and horse serum (para. [0070]). Kamm further discloses/provides motivation that the horse serum is used to induce myoblast fusion and skeletal muscle differentiation.
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 modify Martins’ organoid generating protocol with the high glucose medium and horse serum of Kamm. Doing so would induce myoblast fusion and skeletal muscle differentiation.
Claims 13 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Martins and Kamm as applied to claims 1 – 12 and 14 above, and further in view of Shi et al. (Modeling the Pathogenesis of Charcot-Marie-Tooth Disease Type 1A Using Patient-Specific iPSCs Stem Cell Reports, 2017; 10, 120-133; hereinafter Shi).
Regarding claims 13 and 15, Kamm discloses utilizing physiological relevant cells, such as Schwann cells, responsible for axon guidance, myelination, nerve repair, etc. in order to study demyelinating neuropathies, such as Charcot-Marie-Tooth disease (para. [0173]). Shi discloses the generation of hiPSC lines from two CMT1A patients as in vitro cell model (Abstract). Shi provides the motivation for using the cells derived from the CMT1a patients by disclosing that their result may have important implications for the uncovering of the underlying mechanism and development of a promising therapeutic strategy for CMT1A neuropathy.
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 modify the cells of Martins and Kamm for the CMT1A hiPSC cells of Shi. Doing so would allow for generating a promising therapeutic strategy for CMT1A, according to Shi.
Conclusion
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 M-F 9:00A - 5:00P.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WALTER JACKSON III/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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