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 .
Claim Status
Claims 1-12 are pending.
Applicant’s election without traverse of the invention of group II (claims 3-10) drawn to a method for producing a myotube in the reply filed on 03 August 2026 is acknowledged. Claims 1-2, and 11-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, claims 3-10 are pending and under examination in the present Official Action.
Priority
The present application claims priority to Japan Application No. JP 2023-100081, filed 19 June 2023. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified untranslated copies of papers required by 37 CFR 1.55 have been received in this application on 09 July 2024.
The earliest possible priority for the instant application is 19 June 2023.
Information Disclosure Statement
The information disclosure statement filed 30 July 2024 fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
Drawings
The drawings submitted on 17 June 2024 are accepted by the Examiner.
Claim Objections
Claims 7-8 are objected to because of the following informalities: abbreviations/acronyms need to be spelled out upon their first encounter in the claims (for example: MYOD1). Appropriate correction is required.
Examiner’s Comment
Throughout the present Official Action, where reference is made to the instant specification, the Examiner will be referring to the publication of the Application (US20240417690 A1).
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 3-10 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 3-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: -----a step of introducing a MYOD1 gene into the human urine-derived cell positive for CD90 to induce the formation of a myotube-----. As written, claim 3 only requires selection of CD90 positive cells but somehow the method is to result in the production of a myotube as set forth in the preamble. It is unclear how a myotube is produced without actually positively requiring a myotube to be produced in the method. It is not apparent as to under what structural or functional parameters the separating a human urine-derived cell positive for CD90 is indicative to the preamble of the claim (a method for method for producing a myotube). Accordingly, a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought. Claims 4-10 are further rejected for their dependency on a rejected base claim.
Claim 3 is further rejected for the recitation of “derived” in the first line of the claim. It is unclear what steps are encompassed by the term “derived” nor what characteristics a myotube must have in order to be considered “derived” from a human urine-derived cell. Unlike the term “human urine-derived cell” the term “derived” is not a term of common usage in the art. Therefore, the metes and bounds of claim 3 cannot be determined and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought by claim 3. Claims 4-10 are further rejected for their dependency on a rejected base claim.
Claims 5 and 6 recite “inducing a myotube” in the first and second lines of each claim. It is unclear what steps are encompassed by “inducing a myotube” and it is unclear what steps are required in order to “induce a myotube” and fall within the scope of claims 5 and 6.
Claims 5 and 6 are further rejected for depending from claim 3 yet reciting “comprising”. This is unclear because it is unclear whether Applicant intends the scope of claims 5 and 6 to supplant the method step recited in claim 3 or whether Applicant instead intends the scope of claims 5 and 6 to encompass the method of claim 3 further comprising the recited step. Accordingly, a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought by claims 5 and 6. Claims 7-10 are further rejected for their dependency on a rejected base claim.
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.
Claims 3-10 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 3 broadly encompasses a method for producing a myotube from human urine-derived cells comprising the sole step of selecting CD90 positive cells from the human urine-derived cells. Thus claim 3 encompasses a vast genus of methods wherein CD90 positive human urine-derived cells are converted (by any presently known, e.g., chemical modification, modifications by contact, culturing in appropriate condition, expression of exogenous sequences, or unknown method) that may or not produce a myotube from a human urine derived cell. There is lack of structure/function correlation for the claimed genus of methods of production of myotubules. In addition, there is no corresponding structure recited in claim 3 for carrying out the function of producing a myotube from the CD90 positive human urine-derived cells. Claim 4 sets forth the human origin of the cells but does nothing to limit the genus of methods claimed and does nothing to provide a structure for carrying out the recited function. Claims 5 and 6 set forth a step of “inducing a myotube” but continue to read on a vast genus of known and unknown methods for “inducing” and continue to fail to set forth a corresponding structure for accomplishing the induction into myotubes. Claims 7-8 positively recite introducing a MYOD1 gene into the human urine-derived cells positive for CD90 which itself provides a structure for producing a myotube but continues to read on a vast genus of introduction which encompasses known and unknown methods for the introduction of genetic material into cells (for example, claims 7-8 encompass any transient or any stable integration of genetic material, any chemical, any protein, and any virally facilitated means for getting the MYOD1 gene into cells, etc.). Claims 9-10 negatively limit the method to those which do not comprise making an induced pluripotent stem cell in the process but these claims continue to read on a vast genus of known and unknown methods for “inducing” and continue to fail to set forth a corresponding structure for accomplishing the induction into myotubes. Thus, the claims broadly encompass a vast genus of methods and the claims fail to recite a corresponding structure for the function of producing a myotube from the CD90 cells.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021). Further, A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). See MPEP 2163(II)(A)(3)(a)(ii).
Here, the specification provides only a single example for the induction of myotubes wherein MYOD1 is introduced into CD90 positive human urine-derived cells (Specification, [0109]-[0110], [0116]). The example teaches the introduction of the MYOD1 gene to CD90 positive human urine-derived cells via the polybrene facilitated infection of the cells with a retroviral vector encoding MYOD1 under control of a TRE3GS promoter (Specification, [0109]-[0110]). No example is provided which teaches the production of myotubes comprising solely the step of selecting for CD90 positive cells and, as far as inducing myotubes is concerned, no example is provided which induces myotubes from CD90 positive cells other than via the introduction of a retroviral vector encoding MYOD1 under control of the TRE3GS promoter.
Thus, the specification does not reasonably convey to the skilled artisan that the inventors had possession of the invention claimed at the time of filing considering the vast genus encompassed, the disclosure of only a single working example, and the lack of a claimed corresponding structure for the function of inducing a myotube. The skilled artisan may be reasonably certain that the inventors had possession of a method of producing myotubes from human urine-derived cells comprising a step of selecting CD90 positive human urine-derived cells and a step of introducing a retroviral vector encoding a MYOD1 gene under control of a promoter into the CD90 positive human urine-derived cells but the same cannot be said for a method of doing so comprising the sole step of selecting CD90 positive cells.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 3-10 are rejected under 35 U.S.C. 103 as being unpatentable over US 2022/0144902, published: 12 May 2022, hereinafter “Takizawa” in view of Manaph, et al. Stem cell research & therapy 9.1 (2018): 189, published: 11 July 2018, hereinafter “Manaph”, Mishra, et al. Scientific reports 10.1 (2020): 18978, published: 04 November 2020, hereinafter “Mishra”, and Dan et al. BMC Molecular and Cell Biology 24.1 (2023): 8, published: 07 March 2023, hereinafter “Dan”.
The applied Takizawa reference has a common inventor as the instant application with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(1). The publication dated for Takizawa is 12 May 2022. The earliest effective filing date of the instant application is 19 June 2023.
Therefore a rejection under 35 U.S.C. 103 CANNOT be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02. Because the reference qualifies as prior art under 102(a)(1), the provisions of MPEP 717.02 do not apply.
Regarding claim 3, Takizawa teaches a method for preparing myotubes from urine-derived cells by introducing a MYOD1 gene into the cells (Takizawa, Abstract). Of note, the method of Takizawa uses the same retroviral vector encoding MYOD1 under control of a TRE3GS promoter and polybrene introduction as the instant application to carry out the induction of the cells to produce myotubes (Takizawa, FIG. 2, [0104]-[0105]).
Thus, the only difference between the method of Takizawa and the instantly claimed method is the fact that Takizawa does not teach a step of selecting CD90 positive cells from the urine-derived cells.
Takizawa is not silent as to the relevance of the myotubes produced and in fact teaches that the myotubes are produced from urine-derived cells of humans with Duchenne muscular dystrophy (DMD) (Takizawa, [0111], Abstract). Takizawa also teaches that the method is an improvement over existing direct reprogramming methods which were a challenge because of extra morphology selection steps and relatively long length of time for induction (Takizawa, [0008]). Thus, a person having ordinary skill in the art would have known from Takizawa that direct reprogramming methods for urine-derived cells were ripe for improvement and that such methods were in the field of investigative testing methods and therapies for DMD.
Manaph teaches that urine-derived cells contain a population of urine stem cells (USC) and that those stem cells express a variety of markers including those associated with mesenchymal stem cells and that those markers include CD90 (Manaph, page 2, first full paragraph, and “Urine stem cells USC” heading). Manaph teaches that USCs have high expandability compared to other stem cell types and that USCs in fact comprise MSCs (Manaph, page 2, last partial paragraph; Table 1). Manaph also specifically teaches that USCs are useful for the generation of skeletal muscle cells and suggests to use them as a therapy for DMD because they are more effective and generate more differentiated cells than other traditional stem cells like ESCs and iPSCs (Manaph, page 8, “Muscle engineering” heading). Thus, a person having ordinary skill in the art knew from the teachings of Manaph that human urine-derived cells contain USCs and that those USCs contain MSCs expressing CD90 and that USCs are suggested for the production of skeletal muscle cells as a therapy for DMD because of their distinct advantages over ESCs and iPSCs. Mishra teaches that CD90 expression promotes enhanced myogenic differentiation in MSCs (Mishra, Abstract; Figure 5). Mishra also teaches that UCT MSCs (a type of MSC which more highly expresses CD90) more effectively differentiate into myotubes displaying morphology similar to bona fide myogenic cells than MSCs expressing lower levels of CD90 (Mishra, page 2, last partial paragraph; page 5, first partial paragraph). Mishra also teaches that the MSCs expressing higher levels of CD90 are a valuable source of cells for therapy and modelling of disease processes (Mishra, page 6, second full paragraph). Thus, a person having ordinary skill in the art would have known from Mishra that CD90 is a specific marker for MSCs which have enhanced myogenic differentiation potential and which differentiate into myotubes with morphologies similar to bona fide myogenic cells. Finally, the use of flow cytometry to select for CD90 positive cells from urine-derived cells is a technique that was well known to a person having ordinary skill in the art before the effective filing date of the claimed invention (See Dan, page 3, first full paragraph).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have selected CD90 positive human urine-derived cells in a method for producing myotubes and to have arrived at the invention claimed in instant claim 3 with a reasonable expectation of success because they would have been motivated to do so from the teachings of Manaph and Mishra. Manaph teaches that urine-derived cells comprise MSCs and suggests to use USCs from urine-derived cells specifically for skeletal muscle differentiation in a DMD context and Mishra teaches that CD90 specifically is a marker for MSCs that more effectively differentiate into myotubes. There would have been a reasonable expectation of success in combining the teachings of Takizawa, Manaph, and Mishra insofar as all are concerned with cell therapies for muscle disorders and Manaph and Takizawa specifically teach urine-derived cells as a source of cells for DMD therapies while Mishra teaches characteristics of MSCs (which Manaph teaches are found within urine-derived cells) that make them more effective at differentiating into skeletal muscle cells.
Regarding claim 4, Takizawa teaches to use cells from a DMD patient.
Regarding claims 5 and 6, Takizawa teaches to induce differentiation of the urine-derived cells into myotubes.
Regarding claims 7 and 8, Takizawa teaches to introduce the MYOD1 gene into the urine-derived cells.
Regarding claims 9 and 10, the method of Takizawa is a direct reprogramming method which does not comprise generating an induced pluripotent stem cell.
Additional Comments
Kim, Ellis Y., et al. "Direct reprogramming of urine-derived cells with inducible MyoD for modeling human muscle disease." Skeletal muscle 6.1 (2016): 32, cited by Applicant on the IDS submitted on 30 July, 2024 is another piece of relevant prior art for the instant invention. Kim teaches another direct reprogramming method for producing myotubes from urine-derived cells (Kim, Abstract).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDAN THOMAS TINSLEY whose telephone number is (703)756-5906. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/BRENDAN THOMAS TINSLEY/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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