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 reply dated 02/26/26 has been received. No claim is amended.
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.
The rejection of claims 12-15 and 23-30 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn,
Claim Rejections - 35 USC § 102
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.
Claim(s) 12,14-15,23-27,29 and 30 remain rejected under 35 U.S.C. 102a1 as being anticipated by Hu et al. (BMC Cancer 2011, 11:82, 13 pages) as evidenced by Aubert (PNAS September 30, 2003 vol. 100 suppl. 1, 11836–11841).
Claim 1 is drawn to a method comprising culturing neural stem cells in a differentiation medium for a time and under conditions to for neuronal cells wherein the differentiation medium comprises a serum-free neural stem cell culture medium and a serum-free supplement comprising at least on gamma secretase inhibitor. The claim also recites wherein cell clumping is reduced by at least 65% compared to culture without inclusion of a gamma secretase inhibitor.
Hu taught isolating of neural stem cells from brains of mouse embryos. Single cells were primarily plated in serum-free Dulbecco’s modified Eagle’s medium (DMEDM)/F12 medium containing 20 ng/ml basic fibroblast growth factor, 20 ng/ml epidermal growth factor (EGF), B-27 neural supplement and were fed every 3 days by adding fresh medium supplemented with gamma secretase inhibitor (GSI), see page 3. Hu taught that NSCs normally proliferate and form neurospheres but in the presence of a GSI, proliferation and neurosphere formation is decreased. Hu did not teach that the cells exhibited reduced clumping in the presence of the GSI. Hu does not teach how much neurosphere formation (cell clumping) was decreased (claim 12, 65% and claim 15, 75%). However, because Hu teaches carrying out the method steps as claimed, it is held that the effect would be inherent to the method.
The specification, at para 73, teaches that the clumping is the result of higher cell density due to increased proliferation that occurs in the absence of GSI. Accordingly, Hu taught GSI led to augmented differentiation and attenuated proliferation, which is consistent with reduced clumping.
With regard to claims 14,25-27,29 and 30, Hu taught use of both 0.25 and 25 micromolar GSI (see supplementary materials).
Applicant argues that Hu fails to teach, either explicitly or inherently, the claimed specific quantitative reduction. Applicant asserts that the specification demonstrates this outcome is not necessary or inevitable. Applicant points to paragraph 84 that states, “…while the effect of cell clump reduction during the differentiation of hPSC-derived NSCs may be a common feature of the gamma-secretase inhibitors tested herein, their efficacy varies.” Thus, Applicant argues that the disclosure contradicts the notion that any GSI used in a differentiation method will necessarily result in a clumping reduction of at least 65%.
Applicant asserts that Hu’s Supplementary Figure 1 showing a 65% reduction in clumping does not establish anticipation because it is a single data point.
These arguments are not persuasive because they are not commensurate in scope with the claims. The claims are not limited to a specific GSI and concentration. Hu meets the limitations recited in the method steps and thus the outcome of such would be the same as that of the claims. Applicant argues that the current method is a 2D culture method and Hu uses a 3D culture method. Again, the claims are not limited to a 2D culture method and there is no evidence of record that the 2D method is responsible for a higher reduction in clumping that cannot be achieved by the methods of Hu. The methods of Hu do attain a high reduction of clumping as shown by Supplementary Figure 1. There is no evidence that this Figure is not exemplary. Hu explicitly teaches the methods precisely as claimed and any effect of carrying out the method would be inherent absent evidence to the contrary. If there are differences in effect, these should be recited in the claims. For example, perhaps an additional culture component, a GSI concentration difference or duration in culture etc.
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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.
Claim(s) 12,13,28 remain rejected under 35 U.S.C. 103 as being unpatentable over Hu et al. (BMC Cancer 2011, 11:82, 13 pages) as evidenced by Aubert (PNAS September 30, 2003 vol. 100 suppl. 1, 11836–11841) in view of Groth (Seminars in Cell & Developmental Biology, Volume 23, Issue 4, June 2012, Pages 465-472).
Hu meets the limitations of independent claim 12 as set forth above. Hu did not teach the specific identity of the GSI used. However, may GSIs were known in the art at the time of filing including Compound E, LY411575 and MK-0752 which are each recited in claims 13 and 28.
For example, Groth taught numerous GSIs as inhibitors of Notch signaling which is the mechanism of action in the teachings of Hu as well as the instant invention. Among the GSIs discussed by Groth are those recited in claims 13 and 28, Compound E, LY411575 and MK-0752. Groth discusses that while GSIs were originally developed to inhibit Notch signaling in the treatment of Alzheimer’s Disease, the were also being explored for treatment of other diseases through affecting Notch signaling.
It would have been obvious at the time of filing to use any of Compound E, LY411575 and MK-0752 as GSIs in the method of Hu in culture of NSCs to affect the proliferation/differentiation of NSCs to arrive at the invention as claimed. One would have been motivated to turn to Groth for the choice of GSI because Hu does not reveal the specific identity of GSI used and Groth provides a review of numerous GSIs, their structures and mechanisms of action. One would have had a reasonable expectation of success in making the combination and would have arrived at the recited GSIs as Groth taught LY411575 and Compound E as being in the same class and having high potency and specificity.
Applicant points to paragraph 84 supporting the concept that the efficacy of various GSI in reducing clumping varies. Applicant argues that the selection of a particular GSI and concentration to achieve the claimed, significant reduction is not a matter of simple substitution or a predictable result. In response, because Hu generically referred to use of a GSI, one would turn to the art to identify various GSIs for use. Hu taught using a 10-fold range and varying efficacies between 0.25mm and 25mm. Thus, it would have been obvious to try various concentrations of various GSIs to choose one that led to desired culture characteristics. An ordinary artisan would recognize this as a matter of routine optimization rather than inventive ingenuity. According to MPEP 2143.05 (II), “In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions. see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.").
Conclusion
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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/VALARIE E BERTOGLIO/ Primary Examiner, Art Unit 1632