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 .
DETAILED ACTION
STATUS OF THE CLAIMS: Claims 1, 16, 24, 29-32, 34, 39, 43, 96-97, 99, 102, 106, 109, 111 and 116-118 are pending in this application.
Election/Restrictions
Applicant’s election of species in the reply filed on March 13, 2026 is acknowledged. All claims were examined.
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(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, 16, 24, 29-32, 34, 39, 43, 96-97, 99, 102, 106, 109, 111 and 116-118 (including claims dependent thereon or claims that relate back to claim 1) 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 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.
The claims are drawn to N-oxides, solvates, dimer or trimers. But the numerous examples presented all failed to produce N-oxides, solvates, dimer or trimers. These cannot be simply willed into existence. As was stated in Morton International Inc. v. Cardinal Chemical Co., 28 USPQ2d 1190, “The specification purports to teach, with over fifty examples, the preparation of the claimed compounds with the required connectivity. However…there is no evidence that such compounds exist…the examples of the '881 patent [U.S. Patent # 4,062,881] to not produce the postulated compounds…there is…no evidence that such compounds even exist.” The same circumstance appears to be true here: there is no evidence that and N-oxides, solvates, dimer or trimers of these compounds actually exist; if they did, they would have formed.
Additionally, 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 thus use the invention commensurate in scope with these claims. N-oxides are non-enabled since generally not all solvents can form N-oxides with all compounds. There is no process enabling such a scope in the specification. Note Vippagunta provided herein who flatly states on p. 18, section 3.4 the following: “Predicting the formation of N-oxides, solvates, dimer or trimers of a compound…Is complex and difficult.” Applicants’ own specification confirms this despite numerous examples presented, none of the final products were obtained as N-oxides, solvates, dimer or trimers. The skill in the art of N-oxides, solvates, dimer or trimers preparation is quite high. Hence, applicants must show that N-oxides of the compounds can be made, or limit the claims accordingly.
Claims 1, 16, 24, 29-32, 34, 39, 43, 96-97, 99, 102, 106, 109, 111 and 116-118 (including claims dependent thereon or claims that relate back to claim 1) are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for unlabeled subgenus of compound of formula I or pharmaceutically acceptable salt thereof, does not reasonably provide enablement for and subgenus of compound of formula I labeled with deuterium (“deutero”) at various position or pharmaceutically acceptable salt thereof as recited in instant claims. 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.
In evaluating the enablement question, following factors are considered. Note In re Wands, 8 USPQ2d 1400 and Ex parte Forman, 230 USPQ 546. The factors include: 1) The nature of the invention, 2) the state of the prior art, 3) the predictability or lack thereof in the art, 4) the amount of direction or guidance present, 5) the presence or absence of working examples, 6) the breadth of the claims, and 7) the quantity of experimentation needed.
1. The nature of the invention and the state of the prior art:
The invention is drawn to a compound of Formula I:
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wherein the variable groups R1, R2, R3 … to name a few, include besides other variable groups a deuterium isotope or a pharmaceutically acceptable salt thereof. The scope of the genus of the compound of formula I shown above includes besides other various variable groups, D, an isotopic variant of H, thereof at many positions of the variable groups
Even a cursory calculation of the number of compounds embraced in the instant formula I based on the generic definition of alkyl, aryl, heteroaryl, heterocyclyl, substituted aryl, heteroaryl, cycloalkyl and other optional substituents of substituents etc. would result in trillions and trillions of compounds if not more. This is of course not the accurate number and the true number of compounds would far exceed this number of compounds. Thus, the genus embraced in these claims is too large and added to that any pharmaceutically acceptable salt thereof would further expand the scope of compounds. Adding deuterium as isotopic variation of H would result in trillions or more compounds. In addition, the core rings are variously substituted with both reactive groups and non-reactive groups and claim 1 merely recites D thereof of such a genus of compounds which by itself would now include at least trillions of compounds multiplied by trillions of compounds for the salts and then multiplied by trillions of compounds based on the deuterium compounds.
As recited, instant claim 1 is reach thorough claim wherein based on the fact that the number of compounds of formula I disclosed in the specification, it is claimed that any compound of the genus of formula I depicted above can be labeled with atoms of deuterium isotope at any variable groups for which there is no enabling disclosure.
Isotope labeling, in general, is a specialized art. Careful design and performance of synthesis of suitable precursor is needed not only to rapidly make the labeled compound but also to separate starting precursor from the desired final product. A reaction, which works for a particular precursor, may not work for another precursor. The art is not predictable. Thus, the breadth of the instants claims which is broad to include any available position for isotope labeling and use of the resultant compound lacks adequate support in the specification. The same is true for various other radiolabels or isotope where one need to design a suitable precursor and develop a process for each compound. See Atzrodt et al. Angew. Chem. Int. Ed. 2007, 46, 7744-7765 and Hulikal, V. Deuterium Labeled Compounds in Drug Discovery Process-Abstract, www.hwb.gov.in/htmldocs/nahwd2010/L15.pdf.
For example, if the process involves replacement of a halogen with deuterium by catalytic deuteration with D2 then presence of halogen in various variable groups of a compound of formula I will also undergo such a replacement reaction. In addition, the presence of unsaturated groups will also undergo deuteration. Similarly direct exchange of H with D will occur any available position not necessary or specifically. The Specification merely suggests deuterium isotopic variant for H but does not teach or suggest how to perform such an isotopic labeling process. Likewise, in instant specification, there is no teaching of making deuterium labeled compound in compounds of the genus shown in Tables and others as well as Examples. In addition, there is no single example in the specification showing how to perform the deuterium labeling. Given the general nature of the isotopic labeling embraced, it would not be possible for one trained in the art to redeem such an isotopic labeling as a routine process.
Careful design and performance of synthesis of suitable precursor is needed not only to rapidly make the labeled compound but also to separate starting precursor from the desired final product. A reaction, which works for a particular precursor, may not work for another precursor. The art is not predictable. Specification offers no teaching or suggestion for labeling with deuterium isotope.
2. The predictability or lack thereof in the art:
Hence the process as applied to the above-mentioned deuterium labeled compounds claimed by the applicant with a huge genus of variously substituted compounds of formula I to be labeled is not art-recognized process and hence there should be adequate enabling disclosure in the specification with working examples to make the compound of formula I with deuterium isotope claimed.
The amount of direction or guidance present:
Examples illustrated in the experimental section or written description offer no guidance or teachings as to the process of making variously substituted compound of formula I labeled with deuterium. Examples of unlabeled compounds shown therein cannot be deemed as objective enablement for any isotope and one needs guidance for precursor selection and labeling as there is no guidance provided in the specification for labeling with deuterium and the process of making them.
The presence or absence of working examples:
Although examples show the process of making instant compounds, as noted above, they are limited to process of making unlabeled compound of formula the subgenus not the corresponding compounds labeled with deuterium. There are no representative examples showing the viability of the process for plurality of variable groups labeled with deuterium isotope generically embraced in the instant claims.
The breadth of the claims:
Specification has no support, as noted above, for all deuterium labeled compounds of formula I and there is no guidance as to what precursor is suitable for process of making deuterium labeled compounds of formula I with various variable groups and there is also no valid chemical reasoning for one trained in the art to expect that all isotopes would be applicable and share the same use embraced.
The quantity of experimentation needed:
The quantity of experimentation needed would be an undue burden on skilled art in the chemical art since there is inadequate guidance given to the skilled artisan for the many reasons stated above. Even with the undue burden of experimentation, there is no guarantee that one would get the product of desired structure, namely l compound of formula II labeled with deuterium isotope at various position embraced in the instant claims.
Thus, factors such as “sufficient working examples”, the “level of skill in the art and predictability, etc. have been demonstrated to be sufficiently lacking in the case for the instant claims.
Also note MPEP 2164.08(b) which states that claims that read on "... significant numbers of inoperative embodiments would render claims nonenabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative.". Clearly that is the case here.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that "a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable".
MPEP §2164.01(a) states, "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 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." That conclusion is clearly justified here and undue experimentation will be required to practice Applicants' invention.
Claim 118 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim 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.
Claim 118 is directed to a method of treating bacterial infections. In light of this, it can be asserted that in spite of the vast expenditure of human and capital resources in recent years, no one drug has been found which is effective in treating all types bacterial infections. In re Hokum, 226 USPQ 353 (ComrPats 1985).
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 above noted factual considerations. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims
The breadth of the instant claims is seen to encompass methods for treating bacterial infections, by administering to a patient in need of such treatment a therapeutically effective amount of the compound claim. Applicant fails to disclose which specific diseases are treated. Thus, the claims are extremely broad.
The nature of the invention
The nature of the invention is the treatment of these disorders through the use of the claimed compound and derivatives thereof. Currently, there are no known agents that treat these diseases all inclusively.
The level of predictability in the art
The treatment of these disorders is highly unpredictable. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The amount of direction provided by the inventor.
The applicant has not demonstrated sufficient guidance provided in the form of administration profiles, combination ratios of the active agents or reference to the same in the prior art to provide a skilled artisan with sufficient guidance to practice the instant treatment of disorders claimed. Further, the applicant discloses that an effective amount of the compound will be administered without providing any direction other than that the compounds of the invention have a high therapeutic index and follows this with a definition readily found in a basic pharmacology textbook. It should be noted that the therapeutic index of a drug in humans is almost never known and is only determined through clinical experience.
The existence of working examples.
There is not seen in the disclosure, sufficient evidence to support Applicant’s claims of treating bacterial infections. 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, 27 USPQ2d 1510 (CAFC). The disclosure does not demonstrate sufficient evidence to support the applicant's claim to the treatment. There are not sufficient working examples or data from references of the prior art to provide a nexus between those examples and a method of treating the disorders with the claimed compound.
The level of one of ordinary skill.
The level of skill is that of one with a doctoral understanding of diseases mediated by bacterial infections therapeutics. Applicant’s data is not convincing as to make the production and use of pharmaceutical compositions comprising the recited compounds feasible without undue, un-predictable experimentation.
The quantity of experimentation.
A great deal of experimentation is required for the method of treating these disorders. Furthermore, direction, in the form of examples, must be shown to determine what an effective dose may be. The references submitted do not demonstrate this. Therefore, one of ordinary skill in the art would require a significant amount of experimentation in order to determine the effective dosage to treat the multitudes of different types of diseases with the claimed compound individually or in combination with other therapeutic agents.
Thus, it can be safely concluded that the instant case fails to provide an enabling disclosure for the treatment of bacterial infections.
Allowable Subject Matter
Claims 1, 16, 24, 29-32, 34, 39, 43, 96-97, 99, 102, 106, 109, 111 and 116-117 will be allowed if amended to overcome the rejections under 35 USC § 112, first paragraph. The composition and compounds were not found to be obvious or anticipated by the prior art of record. The prior art (i.e., WO 2019/226931) does not teach or suggest the composition and compounds substituted in the manner claimed by the Applicant. Thus, these claims will be allowed if amended to overcome the rejections under 35 USC § 112, first paragraph.
Conclusion
Claims 1, 16, 24, 29-32, 34, 39, 43, 96-97, 99, 102, 106, 109, 111 and 116-118 are pending. Claims 1, 16, 24, 29-32, 34, 39, 43, 96-97, 99, 102, 106, 109, 111 and 116-118 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL V WARD whose telephone number is (571)272-2909. The examiner can normally be reached M-F 9am to 5pm.
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/PAUL V WARD/ Primary Examiner, Art Unit 1622
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