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
Applicant’s election without traverse of Group I, claims 1-61 in the reply filed on 10/31/2025 is acknowledged.
Claim 62 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/31/2025.
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 1-61 are 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 1,11,13-15, 30,43, and 45-47 are unclear in reference to the BET pathway. BET is not a signaling pathway but is a family of proteins that binds to chromatin. BET proteins do operate as a complex. Clarification is requested as to how “BET pathway” should be interpreted so the breadth of BET pathway antagonists can be interpreted either as an antagonist of the BET proteins themselves or other proteins that act along with the BET proteins at the chromatin. Claims 2-29 are unclear based on their dependency from claim 1. Claims 31-61 are unclear based on their dependency from claim 30.
Claims 29 and 60 contain the trademark/trade name GlutaMAXTM. 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 GlutaMAXTM and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 112a
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 1-61 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 the claimed method of differentiating pluripotent stem cells into mesenchymal stem progenitors wherein the Wnt pathway agonist is a CHIR98014, the “BET pathway antagonist” is a BET inhibitor, the PDGF pathway agonist is a PDGF, does not reasonably provide enablement for ant Wnt pathway agonist other than CHIR98014, any BET pathway antagonist other than a BET inhibitor, and PDGF pathway agonist other than a PDGF. 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/or use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(a)). 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 USPQ2d 1404). Clearly, 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). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case are discussed below.
MPEP §2164.01(a), 4th paragraph, provides that, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
The claims are broadly drawn to culture with a WNT pathway agonist. This encompasses increasing signaling anywhere along the pathway. As discussed by Liu (2021, Signal Transduction and Targeted Therapy, 7:3, pages 1-23), Wnts are a family of secreted glycoproteins. Canonical Wnt signaling (Wnt/b-catenin pathway) acts through stabilizing b-catenin, which then activates transcription of Wnt target genes. Non-canonical Wnt pathways are independent of b-catenin and generally regulate cell polarity as opposed to cell proliferation and differentiation. Thus, different Wnt pathway agonists can generate different cell responses. Additionally, Liu discusses that Wnts can be regulated extracellularly by a variety of different proteins such as glypicans and sFRPs that interact with different Wnts, or intracellularly by miRNAs or small molecule GSK3b inhibitors. GSK3b acts downstream of Wnt binding to its receptor and targets b-catenin for degradation. Thus, activating the Wnt signaling pathway encompasses activation of the pathway at a variety of points along the pathway and through different mechanisms, including activating a single gene that does not lead to the differentiation into a MSC progenitor. The specification teaches, by example, use of CHIR98014. CHIR98014 has a different effect on cells than other Wnt activators such as Wnt3A (see Naujok, BMC Research Notes 2014, 7:273, specifically Figure 2) and other GSK3b inhibitors (see BIO, Figure 2). Noteably, Naujok teaches that the GSK-3b inhibitor, SB216763 (recited in claim, 7) did not activate the Wnt signaling pathway. Thus, the claims, by generically reciting WNT pathway agonist, not only encompass CHIR98014, but also various Wnts as well as inhibitors of the various proteins that inhibit various Wnts (see Liu, Table 2). Because CHIR98014 is the only Wnt activator (agonist) used in the working examples of the specification and because the specification and art at the time of filing fail to disclose other Wnt activators that operate through the same mechanism with the same selectivity and potency, to obtain the claimed results, it would require undue experimentation to determine which other Wnt activators would be effective in the methods as claimed.
Similarly, the claims broadly refer to use of PDGF pathway agonists, and FGF-beta pathway agonists. The Specification teaches only one species for each of these broad genera that encompasses a variety of mechanisms of action at any point along the signaling pathways. With regard to PDGF, for example, the specification teaches use of PDGF, itself, not any downstream signaling activators. Figure 2 of Ai (Drug Discovery Today, Volume 29, Number 7 July 2024, 17 pages) depicts multiple sub-pathways downstream of PDGF binding and the claims encompass use of agonists downstream in only a single sub-pathway which would not predictably have the same effect as activation of the whole pathway at the level of the receptor. Likewise, Figure 2 of Werner (Int. J. Mol. Sci. 2023, 24, 14882. https://doi.org/10.3390/ ijms241914882) depicts the IGF-1 signaling pathway and numerous points where an agonist can be introduced. Figure 3 of Ornitz (WIREs Dev Biol 2015, 4:215–266. doi: 10.1002/wdev.176) shows the highly complex FGF signaling pathway. With regard to BET pathway antagonists, BET is not a pathway. It is a class of molecules that affect chromatin structure. Their binding to chromatin can be antagonized by mimetics that to a binding pocket for acetylated lysine (see Filippakopoulos (NATURE REVIEWS | DRUG DISCOVERY VOLUME 13 | MAY 2014 | 337-356).
It is also noted that the Specification does provide any identifying characteristics for the precursor cells other than some morphology characteristics such as nascent mesodermal like morphology, large nuclei and some cells having filapodia. Thus, given that the Specification only teaches a single WNT agonist, a single BET antagonist, PDGF, IGF-1 and FGF-b, themselves, and without identifying characteristics of the desired mesenchymal progenitor cell precursors, it would require undue experimentation how to obtain the desired cells using any other culture media components other than CHIR98014, (+)-JQ1, IGF-1, PDGF and bFGF.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALARIE BERTOGLIO whose telephone number is (571)272-0725. The examiner can normally be reached M-F 6AM-2:30PM.
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VALARIE E. BERTOGLIO, Ph.D.
Examiner
Art Unit 1632
/VALARIE E BERTOGLIO/ Primary Examiner, Art Unit 1632