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 .
Election/Restrictions
This action is in response to the papers filed on 05/12/2026. Claims 1-12 are currently pending as per claims filed on 06/16/2023.
Applicant’s election without traverse of Group II, which include claims 10-12, drawn to a method of treatment or using a mesenchymal stem cell, which is genetically engineered to secrete growth-regulated oncogene-alpha (GRO-a) or overexpress GRO-a compared to a parent cell, or GRO-a, to a subject in need thereof in the reply filed on 05/12/2026 is acknowledged.
Claims 1-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim.
The requirement for restriction between Groups I-II is still deemed proper and is therefore made FINAL.
Therefore, claims 10-12 are subject to examination to which the following grounds of rejection are applicable. Claims 10-12 are independent claims.
Priority
The instant application is a 371 of PCT/KR2021/016262 filed on 11/09/2021, which requests claim foreign priority to KOREA, REPUBLIC OF 10-2020-0152280 filed on 11/13/2020.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d), a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Thus, the earliest possible priority for the instant application is November 13, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/15/2023 was filed before the mailing date of the non-final office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 10-12 are objected to because of the following informalities. The recitation of the phrase growth-regulated oncogene-alpha (GROalpha) requires the indefinite article “a” in front of the GRO-alpha in each of the independent claims at the first encounter in the claims or the definite article “the” if after the first occurrence. Appropriate correction is required.
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 10 is 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.
Claim 10 recites “administering a pharmaceutically effective amount of a mesenchymal
stem cell”. As written, it appears the claim requires pieces or portions of an individual mesenchymal stem cell. It would be unclear to a person having ordinary skill in the art how to determine any, “amount of a mesenchymal stem cell”. For the purpose of examination, the intended meaning will be considered to be administering a pharmaceutically effective amount of mesenchymal stem cells.
Claims 11 and 12 are indefinite because there is not recitation of “administration to a subject in need thereof”. The method treating a muscle disease in the absence of any indication that the administering is to a subject in need thereof implies treating a subject by way of prevention if the subject, if fact, does not have a muscle disease. Thus, it is unclear if the method is for treating or preventing the muscle disease in a subject.
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 10-12 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 using engineered MSCs expressing Gro-a or Gro-a to provide anti-cell death effects to mouse myoblast C2C12 cells in vitro, and treating Duchenne muscular dystrophy mouse models using MSCs expressing Gro-a or Gro-a via systemic administration, does not reasonably provide enablement for a method of treating any and all muscle pathologies, nor a method of treating any and all subjects, nor a method of any treatment with prepared food containing Gro-a. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Claims 10-12 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.
While the written description and enablement requirements are separate and generally separable requirements, the instant application fails to meet either requirement for essentially the same reasons, as set forth below.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the patent coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is not based on a single factor but is rather a conclusion reached by weighing many factors (See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter, 1986) and In re Wands, 8USPQ2d 1400 (Fed. Cir. 1988); these factors include the following:
1) Nature of the Invention.
The instant claims are drawn to a method of treating a muscle disease in a subject by engineering MSCs to secrete Gro-a, provide Gro-a as an active ingredient, or provide a combination of both.
2) Scope of the Invention.
The claims broadly encompass methods of treating any and all muscular disease (for example: Myasthenia gravis, polymyositis, Pompe disease, mitochondrial myopathy, ALS) in any subject (for example: human, dog, fish, reptile, bird, amphibian), as well as methods wherein the MSCs are administered via any route to the subject (for example: orally, topically, central catheter). This breadth not only establishes a vast scope needing support in the instant specification and the art at the time of filing to preclude the imposition of undue experimentation on skilled artisans, but also establishes a vast genus of methods in which any subjects are treated for any muscle condition. This genus encompasses, for example, a method of treating frogs experiencing a condition presenting with defective skeletal muscle differentiation by providing a topical administration of Gro-a. The burden is on the Applicant for supporting this genus in a manner sufficient for skilled artisans to believe that Applicant had possession of the claimed invention.
3) Number of Working Examples and Guidance.
The specification provides working examples for the isolation and culture of human placenta-derived mesenchymal stem cells (PL-MSCs) and human Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) followed by co-culture with mouse myoblasts that were incubated with lovastatin to induce cell injury (Pg. 11-12, example 1), culture of Gro-a alone or in combination with a RIP-3 inhibitor with mouse myoblasts that were incubated with lovastatin to induce death of muscle cells (Pg. 14-16, example 3), treatment of a mouse model of Duchenne muscular dystrophy with intravenous and intraperitoneally injected with each of injected with WJ-MSCs and GRO-a. The Specification discloses that GRO-α inhibited the expression of the necrosis markers in a concentration-dependent manner (para [0081], Figures 4C and 4D).
No example is taught in which any other muscle pathology is treated, any subjects other than mouse myoblasts or a MDX mouse model, nor any administration (including with a food composition) other than intravenous and intraperitoneal injection or any dosage used of a health functional food composition or a cell therapy agent comprising GRO-α to treat a muscle disease. Thus, the extent to which undue experimentation may be imposed upon a skilled artisan is entirely weighed by an evaluation of the art at the time of filing.
4) State of the Art.
The use of MSCs to treat muscle pathologies in in vivo models of muscle disease is not new (Biressi, Stefano et al. The Journal of clinical investigation vol. 130,11 (2020)). Indeed Biressi et al. describes “…studies using both intramuscular and systemic delivery in different dystrophic mouse models have examined the potential therapeutic efficacy of MSCs of different tissue origin. Although many studies demonstrate the ability of MSCs to engraft in skeletal muscle, their ability to enhance muscle contractile force is unclear. Studies have also suggested the potential of transplanted MSCs to give rise to MuSCs. Notably, in some of these studies, MSCs derived from nonmurine tissues were successfully transplanted into immune-competent mice, supporting the idea that MSCs have immune-evasive properties. Local and intravenous injections of human adipose-derived stromal cells were able to engraft in muscles of GRMD dogs and express human dystrophin. Stromal cells obtained from human dental pulp were administered to GRMD dogs, resulting in significant engraftment in muscles but only modest human dystrophin expression after systemic multiple deliveries. These findings support the idea that MSCs may exert anti-inflammatory or paracrine effects.” Typically, the injections were intravenous or intramuscular (Pg. 5656-5657, Section: Cells from non–skeletal muscle tissues). Some clinical trials have been shown with MSCs studied for their therapeutic potential in DMD patients (Table 2.)5) Unpredictability of the Art.
The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability M.P.E.P. § 2164.03.
Biressi et al. teaches “These mesenchymal stromal cells, often referred to as “mesenchymal stem cells” (MSCs), are under evaluation as potential cellular therapies for different pathological conditions. However, uncertainties remain because of the extreme heterogeneity of such cells obtained from different tissues and based on different criteria. Furthermore, it is unclear how paracrine effects are likely to be effective, long-term treatments of chronic, degenerative diseases like muscular dystrophies. Nevertheless, studies using both intramuscular and systemic delivery in different dystrophic mouse models have examined the potential therapeutic efficacy of MSCs of different tissue origin. Although many studies demonstrate the ability of MSCs to engraft in skeletal muscle, their ability to enhance muscle contractile force is unclear (Pg. 5656-5657, Section: Cells from non–skeletal muscle tissues, 1st Paragraph).
No teaching in the art at the time of filing has been found to support an oral food composition of Gro-alpha to treat muscle related pathologies. No teachings of administration has been found to support all routes of administration of MSCs or Gro-alpha. In addition, no art has been uncovered for the treatment of muscle condition using MSCs or Gro-alpha in all any and all subjects.
Thus, the art at the time of filing evidences unpredictability in the treatment of any muscle pathology with MSCs and/or Gro-alpha, of the treatment of any muscle pathology using any route of administration with MSCs and/or Gro-alpha, of the treatment of any muscle pathologies with food compositions containing Gro-alpha, of the treatment of any muscle pathologies found in any and all subjects because the art at the time of filing lacks teachings of methods of treating anything other than muscle pathologies related to DMD in mouse models of DMD, canines, and humans with specific routes of administrations.
As well, the claims are drawn to incredibly large genera of administration modes, skin conditions, and subjects. The physiological art is recognized as unpredictable. (MPEP 2164.03.) In cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved. It is not a question of safety but one of predictability. The claims require administration by many routes that are not potentially able to deliver enough “mesenchymal stem cells” to achieve the end results in humans (like oral administration). Further, the claims are drawn to a genus of skin conditions encompassing conditions in which mesenchymal stem cells engineered to excrete Gro-alpha and/or Gro-alpha are not recognized as a treatment because the factors causing the disease do not implicate Gro-alpha at all.
This raises issues under description as well as enablement. The description component of the rejection is herein included as you cannot use what you have not described. Furthermore, the enablement of the instant invention has been assessed in light of the specification and the prior art available at the time of filing. "However, claims reading on significant numbers of inoperative embodiments would render claims non- enabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative. Atlas Powder Co. v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984); In re Cook, 439 F.2d 730, 735, 169 USPQ 298,302 (CCPA 1971). (see MPEP 2164.08(b). Specifically, the method of administration is more limited than by any as claimed as set forth above. As well, for delivery of MSCs and/or Gro-alpha to specific sites, delivery directly to those sites is needed.
6) Amount of Experimentation Required. The claims have been evaluated in light of the art at the time of filing and found not to be commensurate in scope with the specification. MPEP 2164.05 teaches, “However, the examiner should carefully compare the steps, materials, and conditions used in the experiments of the declaration with those disclosed in the application to make sure that they are commensurate in scope; i.e., that the experiments used the guidance in the specification as filed and what was well known to one of skill in the art. Such a showing also must be commensurate with the scope of the claimed invention, i.e., must bear a reasonable correlation to the scope of the claimed invention.
Consequently, the prior art when combined with the lack of any disclosed direct experimental test of Applicant's hypothesized treatments, shows that one of skill in the art at the time the invention was made would have had no basis to reasonably predict or conclude the claimed methods of preventing or treating could be identified given the lack of details necessary to identify those meeting the necessary functions. Though not controlling, the lack of working examples, is, nevertheless, a factor to be considered in a case involving both physiological activity and an undeveloped art. When a patent applicant chooses to forego exemplification and bases utility on broad terminology and general allegations, he runs the risk that unless one with ordinary skill in the art would accept the allegations as obviously valid and correct, the PTO may, properly, ask for evidence to substantiate them. Ex parte Sudilovsky, 21 USPQ2d 1702, 1705 (BPAI 1991); In re Novak, 134 USPA 335 (CCPA 1962); In re Fouche, 169 USPQ 429 (CCPA 1971).
In view of the breadth of the claims, the lack of guidance in the specification for treating any subject with any muscle related pathology by any route of administration of MSCs and/or Gro-alpha, and the unpredictability evidenced in the art at the time of filing, it would require undue experimentation for a skilled artisan to use the invention claimed. Further, in an unpredictable art, the disclosure of limited examples utilizing MSCs in vitro and in a mouse model of DMD, the teaching of only specific routes of administration, and the lack of a teaching of treatment of any and all muscle conditions would represent to the skilled artisan that applicants were not in possession of claimed genus.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KODYE LEE ABBOTT whose telephone number is (703)756-1111. The examiner can normally be reached M-F 8-5.
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/KODYE LEE ABBOTT/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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