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 .
Status of claims
Claims 1-3, 5-10, and 12-17 are pending and under exam. Claims 4, 11 and 18-24 are cancelled.
WITHDRAWN REJECTIONS
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.
Claims 1-3, 5-10, 12-20, and 22-24 were 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.
It is noted that the claims were rejected for not providing support that the FGF4 alone was sufficient for inducing differentiating into mature ventricular cells. Applicants argued that “whether the resulting cell population is "purely ventricular" is not an appropriate basis for denying support from the written description support for the claimed differentiation methods.” Additionally, Applicants argued that “the claimed inventions are supported by the finding that differentiation in a medium comprising FGF4 promotes differentiation toward mature ventricular cardiomyocytes. Since AA is an optional additional component that may be further included, the support for the claimed inventions does not depend on demonstrating a separate or additional effect of FGF4 + AA over FGF4 alone.”
Applicants’ arguments were found persuasive and the rejection is withdrawn.
Claim 1-3, 5-10, 12-20 and 22-24 were rejected under 35 USC 112(a) as failing to comply with the enablement requirement.
Applicants’ claims were rejected for not accurately tracing the differentiation protocol tracing the FGF4 addition. Applicants argued that “the claimed inventions are supported by the finding that differentiation in a medium comprising FGF4 promotes differentiation toward mature ventricular cardiomyocytes. Since AA is an optional additional component that may be further included, the support for the claimed inventions does not depend on demonstrating a separate or additional effect of FGF4 + AA over FGF4 alone.”
This rejection is withdrawn following Applicant arguments.
MAINTAINED REJECTION
Claim Interpretation
It is noted that at [0050] of the specification notes that “the term “stem cell” refers to pluripotent stem cells comprising embryonic stem cells and induced pluripotent stem cells derived from the inner cell mass in the blastocyst of an early-developmental-stage embryo having pluripotency;” claim 3 and [0051] indicate that “the stem cells are preferably embryonic stem cells, induced pluripotent stem cells, or adult stem cells, but are not limited thereto.” As such all stem cells are interpreted to read on the claimed “Stem cells.”
Claims 1-3, 5-10, and 12-17 remain 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 claims contain 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.
It is submitted that the claims still encompass any and all stem cells. Applicants asserted that “Sepac et al. cited on page 10 of the Office Action allegedly describes that hiPSCs exhibit lower differentiation efficiency than hESCs. Since iPSCs are reprogrammed cells, it may be readily understood that iPSCs can exhibit lower differentiation efficiency than ESCs.” It is noted that the issue is not whether a person of ordinary skill in the art could adapt the disclosed methods to additional stem cell types, but whether the specification reasonably conveys to those skilled in the art that the inventors were in possession of the full scope of the claimed invention.
The present claims encompass differentiation of cardiomyocytes from any stem cell, falling within the scope of the claims. However, the specification describes only a limited subset of stem cell types and does not provide representative examples or other disclosures sufficient to demonstrate possession of methods applicable across full breadth of the claimed genus. Nor does the specification identify characteristics of stem cells that are amenable for differentiation to cardiomyocytes upon treatment with FGF4.
Applicant’s contention that the disclosed methods may be applied to additional stem cell is directed to what a person of ordinary skill in the art might be able to accomplish after reading the specification. Such an argument pertains to enablement rather than written description and does not remedy the lack of disclosure demonstrating that the inventors were in possession of the full claimed genus at the time of filing.
Accordingly, the specification does not reasonably convey possession of the full scope of the claimed invention.
Claims 2-3, 5-10, and 12-17 are rejected for their dependency on the rejected claims.
Claim 1-3, 5-10, and 12-17 remain rejected under 35 USC 112(a) as failing to comply with the enablement requirement.
It is noted that the claims encompass differentiating any stem cell into cardiomyocytes using a medium comprising FGF4, without limitation as to stem cell type, developmental stage, origin or required cofactors. The specification however only discloses a single working example involving differentiation of a specific human embryonic stem cell line (BG01), treated with FGF4, FGF10 and other factors during days 5-15 of an already initiated differentiation protocol. The specification does not provide guidance regarding optimization of the claimed factors for to other pluripotent (stem) cells.
The term stem cells encompasses neural stem cells, hematopoietic stem cells, MSCs, intestinal stem cells, cancer stem cells, ESCs or iPSCs.
It is pointed out that the prior art did not teach that any kind of adult stem cells differentiate into cardiomyocytes. For example, Mashiach taught that “Human embryonic stem cells (ESC) are undifferentiated and are endowed with the capacities of self-renewal and pluripotential differentiation. Adult stem cells renew their own tissue, but whether they can transdifferentiate to other tissues is still controversial.” (See Mashiach Abstract). Further Batalov taught that “Human cardiomyocytes derived from pluripotent stem cells (PSCs) are the only viable source for new cardiomyocytes currently available. The reason is that adult cardiomyocytes are non-proliferative, and adult stem cells are difficult to differentiate into cardiomyocytes.” (See Batalov; p. 72; col. 1; para 1). Thus, the art recognized that not all stem cell types are readily known to differentiate into cardiomyocytes, and the prior art acknowledged the unpredictability in differentiation of cardiomyocyte differentiation from adult stem cells. It is also noted that the specification did not teach that all or representative number of adult stem cells can differentiate into cardiomyocytes. The specification only demonstrated that BG01 embryonic stem cells can differentiate into cardiomyocytes.
Due to the lack of teachings in the art regarding use of FGF4 in all stem cell types, and the recognized unpredictability in the area of cardiomyocyte differentiation, a large amount of guidance and teachings would be necessary in order to be enabling for methods of such.
Claims 2-3, 5-10, and 12-17 are rejected for their dependency on the rejected claims.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JAGAMYA NMN VIJAYARAGHAVAN/
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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