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 .
Election/Restrictions
Applicant's election with traverse of Group V, claims 35 and 38 in the reply filed on 1/30/2026 is acknowledged. The traversal is on the ground(s) that the technical feature of a culture medium comprising LY2157299 does not make a contribution over the prior art in view of Semechkin et al. (US 2016/0122711 A1) ("Semechkin"). Applicant respectfully disagrees with the Office's conclusion and submits that all of the pending claims now require the inclusion of a culture medium comprising AM580. Applicant therefore submits that the subject matter recited in the Groups V and VI claims is linked by a technical feature that is not taught or suggested by Semechkin and makes a contribution over the prior art in view of Semechkin.
This is not found persuasive because Semechkin was sufficient to break unity with the now cancelled claims and the limitation of LY2157299 was recited in claim 38 which was restricted to elected Group V.
The requirement is still deemed proper and is therefore made FINAL.
Claim 49 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 1/30/2026.
Claims 36 and 37 have been cancelled.
Claims 40-48 are new.
Claims 36, 38 and 40-48 are examined in the instant application.
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 36, 38 and 40-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
a method of differentiating pluripotent stem cells into photoreceptor neuron cells, comprising the steps of:
culturing pluripotent stem cells in a culture medium comprising 7.5μM of LY2157299 to obtain ectoderm cells,
culturing the ectoderm cells in a culture medium comprising 7.5μM of LY2157299 and 0.5μM AM580 to obtain photoreceptor neurons,
does not reasonably provide enablement for:
differentiating pluripotent stem cells or ectoderm cells into photoreceptor neurons in one step, and
with any concentration of LY2157299 or AM580.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
While determining whether a specification is enabling, one considers whether the claimed invention provides sufficient guidance to make and use the claimed invention, if not, whether an artisan would have required undue experimentation to make and use the claimed invention and whether working examples have been provided. When determining whether a specification meets the enablement requirements, some of the factors that need to be analyzed are: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and whether the quantity of any necessary experimentation to make or use the invention based on the content of the disclosure is ''undue'' (In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). Furthermore, USPTO does not have laboratory facilities to test if an invention will function as claimed when working examples are not disclosed in the specification, therefore, enablement issues are raised and discussed based on the state of knowledge pertinent to an art at the time of the invention, therefore skepticism raised in the enablement rejections are those raised in the art by artisans of expertise.
The breadth of the claimed invention encompasses: differentiating pluripotent stem cells or ectoderm cells into photoreceptor neuron cells in one step using any concentration of LY2157299 and AM580.
However, a review of the instantly filed specification teaches that the claimed methods
require a step-by-step differentiation protocol to differentiate pluripotent stem cells or ectoderm cells into photoreceptor neuron cells with specific concentrations for LY2157299 and AM580.
Working Examples
The specification teaches in Figures 2 and 3 that the concentration of LY2157299 and AM580 are critical to practicing the claimed methods. Specifically, the specification teaches starting on pg. 9 line 16 bridge pg. 10 line 3 that to little LY2157299 and AM580 results in no induction of ectoderm and photoreceptor cells respectively and too much results in apoptosis and thus an optimal concentration must be used. The specification teaches on pg. 15 lines 8-12:
“As shown in Figure 2, the results show that in the absence of L Y2157299 or at low concentration of L Y2157299, the ectoderm could not be completely formed, and high concentration of LY2157299 induced cell apoptosis, so the concentration used in the present invention was within the optimal concentration range of L Y2157299.”
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The specification continues on pg. 16 lines 9-12:
“As shown in Figure 3, the results showed that the concentration of AM580 was positively correlated with the photoreceptor non-specific marker PAX6, but when the concentration of AM580 was too high, it would lead to apoptosis.”
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In this regard the specification teaches that 7.5μM of LY2157299 and 0.5μM AM580 was necessary to practice the claimed invention.
Multiple Stages of Differentiation
The pending claims encompass directly differentiating pluripotent stem cells into photoreceptor neuron cells in one step, which is not possible. All pluripotent stem cells must form a germ layer (endoderm, ectoderm or mesoderm) before directing cell differentiation towards a specific cell lineage, i.e. a photoreceptor neuron cell.
Further the art teaches that timing and concentration of growth factors is critical to cell differentiation. For example, Cell Guidance Systems (August 2024, 4 page printout attached) teaches:
“Growth factors are critical to many aspects of cell culture including proliferation, differentiation and cell maintenance. While the effects of too-little growth factors, such as lack of proliferation, are readily apparent, adding too much growth factor, though less obvious can be equally important.
Similar to drugs, as well as their desired effects, growth factors can have a myriad of unwanted side effects. Just as drugs have therapeutic windows in which the drug has efficacy and tolerable side effects, there is an optimal range for growth factors used in culture.” (pg. 1 lines 1-7).
Conclusion
Thus, as set forth above, the claimed invention has two issues of enablement: (i) the concentration of the factors used to produce ectoderm and photoreceptor neuron cells and (ii) the direct differentiation of pluripotent stem cells into photoreceptor neuron cells. However, as the art teaches above, the skilled artisan would find that only through a multi-step differentiation process using specific optimal concentrations of LY2157299 and AM580 can photoreceptor neuron cells be obtained from pluripotent stem cells. Thus, the claims are not enabled for their entire breadth and thus limiting the claimed invention to the scope set forth above is proper.
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 43, 47 and 48 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 43, 47 and 48 contains the trademark/trade name Optiferrin. 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 Optiferrin and, accordingly, the identification/description is indefinite.
Closest Prior Art
The closest prior art for the claimed invention is US 2016/122711 A1 (Semechkin et al.) and US 2020/010801 A1 (Kuroda et al.). While Semchkin and Kuroda teach obtaining retinal pigment epithelial cells and mention both LY2157299 and AM580 in their disclosures, they do not produce or obtain the recited photoreceptor neuron cells, nor do they teach the specific concentrations of LY2157299 and AM580 necessary to successfully obtain photoreceptor neuron cells from pluripotent stem cells.
Conclusion
No claims are allowed. The claims are free of the prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID A MONTANARI whose telephone number is (571)272-3108. The examiner can normally be reached M-Tr 8-6.
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/DAVID A MONTANARI/Examiner, Art Unit 1632
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