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 .
Withdrawn/modified rejections
35 USC 112b rejection on claims 1-7 was withdrawn, because of the amendments/ cancellation of the claims.
35 USC 103 art rejection on claims 1-7 was withdrawn based on amendments and applicant’s arguments,
Claim objection
In claim 1, the phrase “wherein” is grouped with the product collection step. However, the variable temperature stimulation treatment was recited in the activity stimulation step. Therefore, the variable stimulation limitations don’t belong where they are recited.
New rejections
Claim Rejections - 35 USC § 112 (a)
Claims 1, 5-7 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 a mesenchymal stem cell subjected to a specific variable temperature stimulation treatment to simultaneously release G-CSF, Fractalkine, EGF, IL-4, IL-5 and IL-13 does not reasonably provide enablement for any stem cell undergone any modification to simultaneously release G-CSF, Fractalkine, EGF, IL-4, IL-5 and IL-13 after the cell culture, activity stimulation and product collection steps. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to utilize the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, the enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention:
The claims are drawn to a method for producing a modified stem cell that simultaneously releases G-CSF, Fractalkine, EGF, IL-4, IL-5 and IL-13 after cell culture, activity stimulation and product collection steps.
(2) Breadth of the claims:
The instant claim 1 recites any modified stem cell (i.e, any modification and any stem cell) simultaneously releasing G-CSF, Fractalkine, EGF, IL-4, IL-5 and IL-13 after cell culture, activity stimulation and product collection steps.
(3) The state of the prior art:
Prior art on stem cell cryopreservation is mostly directed to improving the post-thaw viability and differentiation capability of stem cells rather than the capability to secrete various factors. Whaley et al., 2021 teaches that cell -specific recommendations should be considered for best post-thaw survivability of cells. Rapid cooling is associated with better cryopreservation outcomes for embryonic stem cells while slow colling is better for hematopoietic stem cells and mesenchymal stem cells (Whaley et al., 2021). A three -step cooling, cryopreservation method for human mesenchymal stem cells (MSCs) is taught by Pravdyuk et al., 2013, cryopreservation by cooling from 0 to -70C , then to -400C, followed by to -80 0Cshowed the highest viabilities and metabolic rates after thawing, compared to their two step and one step freezing protocols. After cryopreservation by three-step cooling protocol MSCs were able to achieve multilineage differentiation . Pogozhykh et al., 2017, investigated changes in cell survival, vital parameters and differentiation potential of placental multipotent stromal cells after temperature fluctuations in the liquid nitrogen steam storage. Post-thaw results of the study showed that the regulation of various genes after cryopreservation procedures varied significantly, resulting over up to ten-fold up or down regulation of adipogenic, chodrogenic and osteogenic genes in the cryopreserved cells compared to the cells that were not cryopreserved.
(4) The predictability or unpredictability of the art:
The current status of the prior art regarding optimum cryopreservation conditions of various stem cells and their post-thaw outcomes appears to vary among different stem cells. While MSCs achieved multilineage differentiation after three step cryopreservation, placental multipotent stomal cells showed significant variations in gene regulation that resulted in up to ten-fold up or down regulation of adipogenic, chodrogenic and osteogenic genes upon subjecting to freeze-thaw cycles, indicating the unpredictability of the art with regards to cryopreservation outcomes of various stem cells. It appears that the art teaching variable temperature stimulations that lead to changes in gene expression is unpredictable. Therefore, while enabling a mesenchymal stem cell subjected to a specific variable temperature stimulation treatment to simultaneously release G-CSF, Fractalkine, EGF, IL-4, IL-5 and IL-13, applicant is invited to provide evidence that the recited factors can occur under any culture conditions in any stem cell type having any modification.
(5) The relative skill of those in the art:
The relative skill of those in the art is high, requiring a graduate degree.
(6) The amount of guidance presented:
Specification has not provided guidance on what modifications in what stem cells result in the simultaneous release of the claimed factors. Therefore, the claims and specification when taken together do not provide guidance to correlating any modification in any stem cell that results in simultaneous release of G-CSF, Fractalkine, EGF, IL-4, IL-5 and IL-13.
(7) The presence of working examples:
Page 7 of the specification recites that the stem cell referred to in the present invention is a mesenchymal stem cell. Comparative example 1, the only working example related to the instant invention discloses the release of the G-CSF, Fractalkine, EGF, IL-4, IL-5 and IL after subjecting a three-step variable temperature stimulation from the cells isolated from adipose tissue. However the specification do not provide any working example correlating other stem cells with modifications other than subjecting to specific variable temperature stimulation to result in simultaneous release of G-CSF, Fractalkine, EGF, IL-4, IL-5 and IL-13.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed above and the high unpredictability and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to make and use the claimed invention within the broad scope as instantly claimed. For example, one of ordinary skill in the art would have to perform an undue amount of experimentation to determine what stem cells would simultaneously release G-CSF, Fractalkine, EGF, IL-4, IL-5 and IL-13 after the cell culture, activity stimulation and product collection steps.
Therefore, the specification does not enable any person skilled in the art to which it pertains, or with which it is nearly connected, to make and use the invention commensurate in scope with these claims.
Claim Rejections - 35 USC § 112(a)
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, 5-7 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.
The purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997).
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include a disclosure of a representative number of species to describe the complete structure of the claimed genus and/or disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
Scope of the invention
The instant claims are drawn to a method for producing a “modified” stem cell that simultaneously release G-CSF, Fractalkine, EGF, IL-4, IL-5 and IL-13 after cell culture, activity stimulation and product collection steps. The genus “modified” indicates any modification to any stem cell and the said stem cell expresses claimed markers simultaneously. The genus “modified” may encompass structural, genetic or any other cellular alterations that may be applicable. However, the specification does not disclose any of such alterations. Instead, the specification discloses what appears to be a simultaneous activation/expression of the genetic structures already possessed by a single species of stem cell, i.e., a mesenchymal stem cell, as a result of a specific variable temperature stimulation recited in the claims. Therefore, it appears that applicant was not in possession of the genus “modified stem cell” which is capable of simultaneously releasing G-CSF, Fractalkine, EGF, IL-4, IL-5 and IL-13, at the time of filling of the claimed invention
Structure/function relationship
The genus of “modified stem cell” encompasses any modification to the stem cell. The genus “modified” may encompass any structural, genetic or other cellular alterations that may be applicable which result in simultaneous release of the claimed factors. The structure of the said genus is not identified because the specification described only one species which is the “activated” mesenchymal stem cell, wherein the activation was caused by subjecting the mesenchymal stem cell to a specific variable temperature stimulation. Further the breadth of any modification to result at the specific expression pattern recited in claim 1 is unpredictable as discussed in scope of enablement.
Conclusion
Specification discloses one species which is the “activated” mesenchymal stem cell that simultaneously express the claimed markers. However, the genus of “modified” is broad, encompassing numerous species under its umbrella as discussed above. Specification does not disclose what modification is done to what stem cells to result in simultaneous release of the claimed markers.
The specification provides evidence for possessing a mesenchymal stem cell subjected to a specific variable temperature stimulation resulting in simultaneous release of the said factors. However, the specification fails to reasonably convey to one skilled in the relevant art that the inventors, at the time of effective filling date of the application, had possession of the genus “modified stem cell” capable of simultaneously releasing G-CSF, Fractalkine, EGF, IL-4, IL-5 and IL-13 Therefore, the examiner concludes there’s insufficient written description for the instantly claimed genera.
Response to Arguments
Applicant’s arguments, see pages 1-15, filed on 07/24/2026, with respect to the rejection of claims 1-7 under 35 U.S.C. 112b and 35 U.S.C. 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn.
However, upon further consideration, a new 35 U.S.C. 112 a scope of enablement and lack of written description rejections were made.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HASHANTHI ABEYRATNE-PERERA whose telephone number is (571)272-6562. The examiner can normally be reached Monday-Friday 7:30 am- 5:00pm.
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/HASHANTHI KOMITIGE ABEYRATNE-PERERA/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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