DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/27/2025 has been entered.
Election/Restrictions
Newly submitted claims 55-56 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: The newly added claims are a therapeutic method which therefore requires treatment, alleviation, and/or reduction of at least one symptom of a disease or disorder. In contrast, the method of the previously presented claims and that have been considered in previous prosecution are a method with the result of a cell fusion event. No therapeutic result is required. As such, the outcome of the method of the new claims is materially different and distinction from the claims that have already been considered.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 55-56 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Previously presented claims 41-54 are under consideration in this office action.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 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 41 and 45-54, as previously presented, are rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
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 require 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 and use the invention based on the content of the disclosure is “undue”.
The claims are drawn to a method of produced a fused cell in a subject in need of regeneration treatment, the method comprising: administering to a subject in need of regeneration treatment of a stem cell and ATP to cause the fusion of the stem cell and a somatic cell in the subject to regenerate or improve a cardiac cell, tissue or organ, wherein said stem cell and said ATP are administered at a site where dysfunction or hypofunction occurs due to cardiac damage or degeneration.
The specification provides specific guidance to and reductive examples of in vitro means of fusing a stem cell with mammalian cardiac cells by treating a co-culture of mouse cardiac cells and bone marrow stem cells with ATP. The specification teaches at the time of the invention, it was established in the art that bone marrow stem cell or hematopoietic stem cell administration for treatment of ischemic cardiac tissue resulted in improved cardiac function and a degree of cardiac repair. At the time of this finding, it was believed that this cardiac repair was due to transdifferentiation of the stem cells into new cardiac tissue. However, others, such as Alvarez-Dolado et al. and Nygren et al. (of record in IDS) demonstrated that at the site of repair was evidence of stem cell fusion with cardiac cells and they hypothesized that this stem cell fusion may be involved in the cardiac repair. From these finding in the art and Applicant's in vitro finding, the inventors propose that administration of stem cells with ATP will result in stem cell fusion with cells at a site of damage and will regenerate or improve cell, tissue, or organ function.
However, the specification fails to provide specific guidance or any evidence that this hypothesis is correct. The specification fails to provide any evidence that administration of ATP with stem cells will predictably result in cell fusion. The specification fails to provide any evidence that administration of ATP with stem cells will predictable result in tissue regeneration or improvement. The specification fails to provide any evidence that a cell fusion event in vivo will cause tissue regeneration or improve tissue function. As such, the specification fails to enable the claimed invention because claims are drawn to a hypothetic method that has not been validated or demonstrated by the specification or art. As such neither the specification nor the art enable the instant claims because neither the art nor the specification provide specific guidance to a method that will predictably result in in vivo cell fusion or a tissue regeneration without further experimentation to validate these results. Such validation would not be considered routine experimentation or mere optimization because the method requires testing to determine that it is more than a hypothesis. As such, neither the specification nor the art enable the claimed method.
The state of the art teaches in vivo, ATP has pleiotropic effects and bind to other cells types in vivo that could hinder its availability to the bone marrow stem cell/myocardial cell fusion events. Jagger et al. (Journal of the International Society of Sports Nutrition 11:28, 2014; pp. 1-7) teaches extracellular ATP stimulates vasodilation by binding to endothelial ATP-selective P2Y2 receptor (p. 1, abstract). Thus it is quite possible that a systemic or event local administration of the bone marrow stem cells and ATP could result in the ATP:P2Y2 receptor binding and sequestration of ATP prior to ATPs arrival at the site of a bone marrow stem cell-myocardial cell fusion event hindering ATP availability at said site. Jagger also teaches that ATP is involved in all aspects of biosynthesis in cells and acts as the primary intracellular energy source. Extracellular ATP and it metabolites are involved in regulating a variety processes including cardiac function, neurotransmission, liver glycogen metabolism, muscle contraction, and blood flow (p. 1, col 1, background section, par 1). Thus, in a multicellular system, such as the claimed patient, where there are multiple cell types present in, at, and between the site of administration and the site of cardiac cell/bone marrow cell fusion site that could utilize and take away the ATP from its intended target site, the site of bone marrow cell and cardiac cell interaction and fusion.
Komukai (Komukai et al. Circ. J. 66:926-929, 2002) teach that ATP administered intravenously is degraded to adenosine (p. 926. Col 1, par 1). Thus degradation following administration also reduces the availability of ATP for cell fusion events. The specification does not provide evidence that adenosine metabolite products will also facilitate the bone marrow cell:myocardial cell fusion. As such, it is not apparent that ATP in a patient will be sufficiently available for the claimed cell fusion event because ATP is quickly metabolized in vivo.
Komukai also teaches that ATP administration also can have the side effects of causing chest pain and discomfort and II AV blockage (p. 1, Table 1). ATP administration has also been reported to cause rapid heart rate, heart palpitations, and increased stress on the heart (Printout from Atp Injection - Uses, Side-effects, Reviews, and Precautions - Biomiicron Pharma - TabletWise – India. https://www.tabletwise.com/atp-injection, printed 4/23/2018, pp. 1-11. See p. 2, line 2 and p. 2, section ‘Atp Injection-Precausions & How to Use’.). If a subject has cardiac dysfunction or hypofunction due to cardiac damage or degeneration as claimed, administering drugs that are cardiac stressors, such as ATP, would not necessarily be therapeutic as would be required by the claims. Thus the art teaches that obstacles of ATP delivery to facilitate a fusion event in vivo. As such, the art suggests unpredictability and specification fails to provide specific guidance that address these obstacles to ATP delivery to provide a reasonable expectation of success in the claimed method.
The instant invention, as claimed, falls under the “germ of an idea” concept defined by the CAFC. The court has stated that “patent protection is granted in return for an enabling disclosure, not for vague intimations of general ideas that may or may not be workable”. The court continues to say that “tossing out the mere germ of an idea does not constitute an enabling disclosure” and that “the specification, not knowledge in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement”. (See Genentech inc v. Novo Nordisk A/S 42 USPQ2d 1001, at 1005). The claimed methods of transfer constitute such a “germ of an idea”.
Therefore at the time of filing the skilled artisan would need to perform an undue amount of experimentation without a predictable degree of success to implement the invention as claimed.
Therefore at the time of filing the skilled artisan would need to perform an undue amount of experimentation without a predictable degree of success to implement the invention as claimed.
Response to Arguments
Applicant's arguments filed 5/27/2025 have been fully considered but they are not persuasive.
Regarding the 112 rejection of record, Applicant continues to traverse the rejection on the same basis addressed previously in prosecution multiple times. As such, Examiner refers back to the previous office action for the rationale as to why the arguments are not persuasive. Applicant also states that new claims 55 and 56 would be enabled. In response, claims 55 and 56 have been withdrawn from consideration as patentably distinct subject matter from the claims previously considered.
No claims are allowed.
This is a request for continued examination of the instant application. All claims are identical to, patentably indistinct from, or have unity of invention with the invention claimed in the earlier application (that is, restriction (including lack of unity) would not be proper) and could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the earlier application. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action in this case. See MPEP § 706.07(b). 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 MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632