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
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Claims 13-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 07/06/2026.
Telephone Conversation: On 8/18/2026 Examiner discussed the claims with Attorney Christopher R Cowles and suggested amendments to claims to place the case in condition for allowance. The suggestion entailed limiting claims to the elected species A-0554 or the broader generic structure [1] by limiting X1-X4 = CR3 and R1 = H or F (see Remarks filed 07/06/2026). Examiner noted that while there is no (102 art), the claims as filed are extremely broad. Applicant argued that the claims are drawn to product and not method (of use) and if there is no prior art, the scope to use does not matter. Examiner argued 112-1 is two prong ‘make and use’ requirement (for ‘scope-of-enablement’ not just ‘enablement’)
Since the elected species A-0554 was found to be free of prior art with respect to anticipation (102), Examination was extended to the full scope of Group 1, claims 1-12.
Claim Rejections – Improper Markush Group
The nonstatutory Markush grouping rejection is based on a judicially approved “improper Markush grouping” doctrine. Claims 1-712 are rejected on the judicially created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature.
A Markush claim contains an “improper Markush grouping” if:
(1) the species of the Markush group do not share a single structural similarity,”
OR
(2) the species do not share a common use.
Members of a Markush group share a "single structural similarity” when they belong to the same recognized physical or chemical class or to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent (see Federal Register, Vol. 76, No. 27, Wednesday, February 9, 2011, p. 7166, left and middle columns, bridging paragraph).
The compounds do not even belong to a recognized single class of compounds because every variable varies having complex meanings and endless permutations and combinations.
Consider, for example, possibilities of X1-X4. The members of the recited cross boundaries of patent classification. The Markush group are so disparate chemically as not to be members of a recognized chemical class of compounds. Further the point of attachment and how these are linked to each render the conceivable compounds structurally different. In view of these claimed elements and the divergent substitutions on the above groups, the physical and chemical properties of claimed compounds are going to be different. Applicants may have to establish the core structure for their claimed compound. It cannot be said that all members of the Markush group have a single structural similarity, based on the above-described structural differences. Specifically, the species of the Markush group do not share a “single structural similarity” because there are no required structural features within each variable definition such that each member of the group would have at least one structural feature, which feature is essential to the activity/function of the claimed compounds, in common. In addition, alternatively usable member of the Markush group for example, the inhibitors or binders of different enzymes (ultimately responsible for the intended use), do not share a common use, absent evidence to the contrary.
The question of whether the lack of a specific statutory basis is a fatal flaw against a holding of an Improper Markush group was decided in In re Harnish, 206 USPQ 300, 305, where the court said, “…we think it should be clear from our actions in Weber and Haas II that we there recognized the possibility of such a thing as an "improper Markush grouping." We were and are aware that it does not have a specific statutory basis …” The court went on to reverse the rejection, (which had been made by the Board under Rule 196(b)) but not on the lack of a specific statutory basis but rather, “Clearly, they are all coumarin compounds which the board admitted to be "a single structural similarity." We hold, therefore, that the claimed compounds all belong to a subgenus, as defined by appellant, which is not repugnant to scientific classification. Under these circumstances we consider the claimed compounds to be part of a single invention so that there is unity of invention…” Thus, the rejection was overturned not because of any lack of a specific statutory basis, but because of the specific facts in the case. The Markush group was held proper in that case, as was the case also in Ex parte Price 150 USPQ 467, Ex parte Beck and Taylor, 119 USPQ 100, and Ex parte Della Bella and Chiarino 7 USPQ2d 1669. Cases where the Markush group was held improper include Ex Parte Palmer, 7 USPQ 11, In re Winnek, 73 USPQ 225, In re Ruzicka, 66 USPQ 226, Ex parte Hentrich, 57 USPQ 419, Ex parte Barnard, 135 USPQ 109, Ex parte Reid, 105 USPQ 251, Ex parte Sun and Huggins, 85 USPQ 516, In re Thompson and Tanner, 69 USPQ 148, In re Swenson, 56 USPQ 180, and In re Kingston, 65 USPQ 371. Note In re Milas 71 USPQ 212 in which the structural difference between vitamin A and D was sufficient to uphold the improper Markush rejection. Also see In re Winnek 73 USPQ 225 and In re Ruzicka 66 USPQ 226 in which structural differences were small and yet a similar holding was maintained. All these cases involved compounds in the art known to be structure-sensitive. Of particular interest is Ex Parte Hozumi, 3 USPQ2d 1059, which reversed an improper Markush rejection “in view of the relatively large proportion of the structure of the compounds in the claimed class which is common to the entire class”. Here, by contrast, the amount in common is none.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1) (emphasis provided).
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 1-12 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 few combinations of the variables of formula 1, does not reasonably provide enablement for the large number of the combination of the variables. For example, it is not seen wherein in the specification enabling disclosure is found, with respect to R1 for anything other than F. Similarly, there is no disclosure as to formula 1 compound with any of X1-X4 being other than CH. 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.
The determination that "undue experimentation" would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the relevant factual considerations.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). These include: (1) breadth of the claims; (2) nature of the invention; (3) state of the prior art; (4) amount of direction provided by the inventor; (5) the level of predictability in the art; (6) the existence of working examples; (7) quantity of experimentation needed to make or use the invention based on the content of the disclosure; and (8) relative skill in the art.
All the factors have been considered with the most relevant factors discussed below:
The claims are drawn to compounds of formula 1
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with substituents layered on top of substituents encompassing large number of conceivable structures that vary widely in physical and chemical properties such as size, molecular weight, chemical functional groups. These properties are known in the art to greatly influence the biological properties of compounds and thus are part and parcel for the ‘how to use’ aspect of the enablement requirement (more on this later, with multiple citations of state of the arf).
How to make prong of the enablement requirement.
Consider the elected species formula 1, as per page 45 of Remarks 07/06/2026 page 45
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There is no compound disclosed for any of [1] having any combination of X1, X2, X3 and or X4 with N. All the compounds made have CH for these Xs except for two one having a F and other with methyl.
Further there is no compound wherein R1 is other than H or F.
Similarly, there is one compound with R2 being other than CH2.
The laundry list for these possibilities as per base claim 1 is:
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The issue is not that any and all such compounds can be made or not. The issue here is working example, guidance and direction with respect which combination of the above variables to make, and if made, would provide for predictable use.
How to use prong of the enablement requirement.
The intended use of the above compounds, according to disclosure:
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Biological properties are unpredictable and are ultimately tide to the chemical structure. For example, in the related analogous pharmaceutical art, Venkatesh, J. Pharm. Sci. 89, 145-154 (2000) (p. 146, left column, “Role of the Development Scientist in Compound Lead Selection and Optimization”, teaches that biological properties are intimately related to structure. Likewise, J. G. Cannon, Chapter Nineteen in Burger's Medicinal Chemistry and Drug Discovery, Fifth Edition, Volume I: Principles and Practice, Wiley-Interscience 1995, pp. 783-802, 784, teaches many caveats in analog design and states
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The close analogy between pharmaceutical and agricultural art as to the underlying structural dependence of biological property is well-known to one of skill in the art. See for example, Linda Hall, How Herbicides Work, Biology to Application, 2014, Alberta Agriculture and Rural Development, Information Management, wherein Linda teaches
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The above on page 1 explicitly teaches that in order to be an active ingredient in any of the claimed methods (as in claims 6-9), certain structural requirements are required, for example, as on page 47
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For similar teachings in the area of fungicides, see El-Nawawy, Journal of Microbiology of the United Arab Republic (1967), 2(2), 115-33, which teaches Relation between chemical structure and biological activity and also Zhang, ACS Appl. Mater. Interfaces 2013, 5, 10953−10959.
Biological activity (control value) of the compounds is compared with structurally ‘similar’ compounds of WO 2017110862, at instant Published Application [0488]- [0493] where the instant elected species compounds of formula [1] are buried. No structural information is present in [0488]-[0493]. Further the compound of 2017110862 has none of the functionalities of the
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(partial structure) of the elected species formula [1]. However, the teaching in the comparison shows that the enhanced benefit of having H instead of alkyl substituents. The compound compared corresponds to compound 7 in 2017110862
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And differs from the elected species in the instant R2 being benzyl.
This compound 7 is higher homolog (that is H vs alkyl) of the instant formamide compound A0482 in paragraph [0489] and [0491] of published Application. See MPEP 2144.09 [R-01.2024] in this regard.
What disease state is controlled in the comparative data in the 0488]- [0493] is unclear.
The R2=benzyl compound with formamide group does not fall under the scope of the elected formula [1].
Thus, major portion of the elected formula [1] already known in the art, with the difference being the formyl
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, as opposed to acyl group corresponding to the X in the above noted Table from 2017110862
The lower homolog, H versus alkyl, in the above discussed compounds provides for better numbers in the comparative data is consistent with the teachings of Venkatesh, Cannon, Linda, El-Nawawy and Zhang: substituents decorating the core template do matter.
This in turn means that the claims are not commensurate in scope with the breadth of enablement in as much as the disclosure is limited to few combinations of the possibilities of formula [1]. There is a substantial gap between what is taught in the specification and what is being claimed. For these reasons, one skilled in the art would be faced with undue amount of research. The specification lacks disclosure sufficient to make and use the invention commensurate with the scope of the claims. Note that in University of Rochester v. G.D. Searle & Co., 68 USPQ2d 1424 at 1438, the screening for over 600 compounds was deemed to be undue. Applicant’s scope of the pictured formula far exceeds this number.
MPEP 2164.01(a) states, “A conclusion of Iack 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. ln re Wright, 999 F.2d 1557,1562, 27 USPQ 2d 1510, 1513 (Fed. Cir. 1993).'' That conclusion is clearly justified here. Thus, undue experimentation would be required to make and use Applicants' invention.
Suggestion:
Limit claims to elected formula [1] (see page 45 of Remarks 07/06/2026)
wherein X1, X2, X3, X4 = CR3 with R3 as defined originally and with R1 = H or F.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625
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