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 .
This is the first action on the merits.
Claims 1-21 are pending and claims 1-7 and 11-13 are under examination. Claims 8-10 and 14 are withdrawn based on the species election and the lack of unity requirement.
Election/Restrictions
Applicant’s election of Group (I) in the reply filed on August 29, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Group (I), drawn to the compounds of formula (I) and compositions thereof, embraced by claims 1-13 was elected by Applicant. Applicant has not pointed to any errors in the Examiner’s analysis of the different inventions. The requirement is still deemed proper and is therefore made FINAL.
Applicant further elected the following species on November 12, 2025:
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and indicated claims 1-7 and 11-14 read on said species. However, claims 8 and 9 do not embrace the elected species and claim14 is found in Group (II) of the lack of unity.
The elected species was not found during the search, and thus, the search was expanded.
Claim Objections
Claim 1 is objected to because of the following informalities: the “or O” in the definition of X and X3 is redundant since the (-CHR5-)mO- and (-CHR5-)dO- groups embraces just oxygen. Appropriate correction is required.
Claim 7 is objected to because of the following informalities: a period is missing at the end of the claim. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1-7 and 11-13 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 pharmaceutically acceptable salts, does not reasonably provide enablement for prodrugs. 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/use the invention commensurate in scope with these claims.
“The [eight] factors to be considered [in making an enablement rejection] have been summarized as a) the quantity of experimentation necessary, b) the amount of direction or guidance presented, c) the presence or absence of working examples, d) the nature of the invention, e) the state of the prior art, f) the relative skill of those in that art, g) the predictability or unpredictability of the art, h) and the breadth of the claims”, In re Rainer, 146 USPQ 218 (1965); In re Colianni, 195 USPQ 150, Ex parte Formal, 230 USPQ 546.
a) Finding a prodrug is an empirical exercise. Predicting if a certain ester of a claimed alcohol, for example, is in fact a prodrug, that produces the active compound metabolically, in man, at a therapeutic concentration and at a useful rate is filled with experimental uncertainty. Although attempts have been made to predict drug metabolism de novo, this is still an experimental science. For a compound to be a prodrug, it must meet three tests. It must itself be biologically inactive. It must be metabolized to a second substance in a human at a rate and to an extent to produce that second substance at a physiologically meaningful concentration. Thirdly, that second substance must be clinically effective. Determining whether a particular compound meets these three criteria in a clinical trial setting requires a large quantity of experimentation.
b) The direction concerning the prodrugs is found in paragraph 0141, pages 26-27. No more than a definition of prodrug is disclosed.
c) There is no working example of a prodrug of a compound the formula (I).
d) The nature of the invention is clinical use of compounds and the pharmacokinetic behavior of substances in the human body.
e) Prodrugs are commonly known in the art as drugs which are administered in an inactive (or less active) form, and then metabolized in vivo into an active metabolite. The state of the arts in prodrugs is provided by Stella (J. Pharmaceutical Sciences, 2010, 99(12), pp. 4755-4765), "So while it may appear to be straightforward to try a prodrug approach, making and identifying the best prodrugs that will work in a specific case is less than routine”, see page 4763, left-hand column. Prodrugs are drugs used to overcome some barriers to the utility of the parent drug molecule. Stella addresses the barriers in the form of questions on page 4763. These barriers include, but are not limited to, solubility, permeability, stability, presystemic metabolism, and targeting limitations. Stella also states, “I have seen in both my academic and work capacity as a consultant that what may appear to be straightforward is most often far from predictable”, see page 4763, left-hand column.
f) The artisans making Applicants' prodrugs as a collaborative team of synthetic pharmaceutical chemists and metabolism experts. All would have a Ph. D. degree and several years of industrial experience.
g) 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). h) The breadth of the claims includes all of the hundreds of thousands of compounds of formula of claim 1 as well as the presently unknown list potential prodrug derivatives embraced by claim 1.
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. Thus, undue experimentation will be required to determine if any particular derivative is, in fact, a prodrug.
The Examiner suggests deleting the term "prodrug", from claims 1-7 and 11-13.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-6, 11 and 13 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Ghosh et al. (WO 2015175994, cited on the IDS).
The reference teaches the following species:
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, see page 16. The reference is replete with other species which render at least claim 1 anticipated. The compositions are taught on page 24, paragraph [0060]. Thus, claims 1-7 and 11-13 are anticipated by the Ghosh et al.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSANNA MOORE whose telephone number is (571)272-9046. The examiner can normally be reached Monday - Friday, 10:00 am to 7:00 pm.
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/SUSANNA MOORE/Primary Examiner, Art Unit 1624