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 .
Non-Final Rejection
The Status of Claims:
Claims 1-14 are pending.
Claims 1-14 are rejected.
DETAILED ACTION
1. Claims 1-14 are under consideration in this Office Action.
Priority
2. It is noted that this application is a 371 of PCT/EP2022/059549 04/09/2022 a 371, which has a foreign priority document EPO EP21167750.5 04/09/2021 and EPO EP21198539.5 09/23/2021.
Drawings
3. The drawings filed on 10/8/23 is accepted by the examiner.
IDS
4. The IDS filed on 10/8/2023 are reviewed by the examiner.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 9-13 are rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPO 475 (D.D.C. 1966).
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 1-14 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 pre-AIA the applicant regards as the invention.
In claim 1, the term ““prodrug " is recited. This expression is vague and indefinite because the specification does not elaborate what is meant by the term “prodrug " in the claim.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 1 recites the broad recitation “A compound of formula (IV)”, and the claim also recites “ particularly of formula (IVa)” which is the narrower statement of the range/limitation.
In the present instance, claim 1 recites the broad recitation “X is CH or N,”, and the claim also recites “ particularly N ” which is the narrower statement of the range/limitation.
In the present instance, claim 1 recites the broad recitation “Y is H or F,”, and the claim also recites “particularly H” which is the narrower statement of the range/limitation.
In the present instance, claim 5 recites the broad recitation “R3 is a C1-3-alkyl ”, and the claim also recites “particularly CH3” which is the narrower statement of the range/limitation.
In the present instance, claim 6 recites the broad recitation “v is 0, 1 or 2”, and the claim also recites “, more particularly 0 or 1” which is the narrower statement of the range/limitation.
In the present instance, claim 8 recites the broad recitation ““A compound of formula (V)”, and the claim also recites “ particularly formula (Va)” ,which is the narrower statement of the range/limitation.
In the present instance, claim 10 recites the broad recitation ““activation of a class I P13K”, and the claim also recites “ in particular PJ3Kα” ,which is the narrower statement of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
In claim 9, the term” a disease” is recited. This expression can be vague because the claim does not explain what kind of a disease can be treated. The examiner recommends to add the specific namesof the disease in the claim.
In claims 9-13, the phrases “ The compound according to claim l for use in the treatment of a disease” and “ The compound according to claim l for use in the treatment of tumor disease, overgrowth syndrome, neurological disease disorder, immunological disease disorder” are recited. This expression can be confusing because these are hybrid claims of combining a compound and a method claim. The examiner recommends to separate them into two different claims.
Claims 9-13 provide the compound according to claim l for use in the treatment of a disease or the compound according to claim l for use in the treatment of tumor disease, overgrowth syndrome, neurological disease disorder, immunological disease disorder, but, since the claims do not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
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In claim 14, the variables” R1”, “R2” , “ R4”, “L2”, “ W2”,” U”, “n” and “W1” are recited. These are vague and indefinite because the claim does not define what is meant by each of the variables in the claim. The examiner recommends to add the definition of each of the variables in the claim.
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 1-13 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for making salts of the claimed compounds, does not reasonably provide enablement for making solvates of the claimed compounds. The specification does not enable any person skilled in the art of synthetic organic chemistry to make the invention commensurate in scope with these claims. “The 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. In the present case the important factors leading to a conclusion of undue experimentation are the absence of any working example of a formed solvate, the lack of predictability in the art, and the broad scope of the claims.
c) There is no working example of any hydrate or solvate formed. The claims are drawn to solvates, yet the numerous examples presented all failed to produce a solvate. 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 do 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 solvates of these compounds actually exist; if they did, they would have formed. Hence, applicants must show that solvates can be made, or limit the claims accordingly.
g) The state of the art is that is not predictable whether solvates will form or what their composition will be. In the language of the physical chemist, a solvate of organic molecule is an interstitial solid solution. This phrase is defined in the second paragraph on page 358 of West (Solid State Chemistry). West, Anthony R., "Solid State Chemistry and its Applications, Wiley, New York, 1988, pages 358 & 365. The solvent molecule is a species introduced into the crystal and no part of the organic host molecule is left out or replaced. In the first paragraph on page 365, West (Solid State Chemistry) says, “it is not usually possible to predict whether solid solutions will form, or if they do form what is their compositional extent". Thus, in the absence of experimentation one cannot predict if a particular solvent will solvate any particular crystal. One cannot predict the stoichiometery of the formed solvate, i.e. if one, two, or a half a molecule of solvent added per molecule of host. In the same paragraph on page 365 West (Solid State Chemistry) explains that it is possible to make meta-stable non-equilibrium solvates, further clouding what Applicants mean by the word solvate. Compared with polymorphs, there is an additional degree of freedom to solvates, which means a different solvent or even the moisture of the air that might change the stabile region of the solvate.
h) The breadth of the claims includes all of the hundreds of thousands of compounds of formula (IV) or (IVa) as well as the presently unknown list of solvents embraced by the term "solvate". Thus, the scope is broad.
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 practice Applicants' invention.
The claims 11-12 set forth the treatment of tumor disease or a solid tumor generally. However, there never has been a compound capable of treating tumor disease or a solid tumor or cancer generally. There are compounds that treat a range of tumor diseases or solid tumors or cancers, but no one has ever been able to figure out how to get a compound to be effective against tumor disease or a solid tumor or cancer generally, or even a majority of tumor diseases or solid tumors or cancers. Thus, the existence of such a “silver bullet” is contrary to our present understanding in oncology. Even the most broadly effective antitumor agents are only effective against a small fraction of the vast number of different cancers known. This is true in part because cancers arise from a wide variety of sources, such as viruses (e.g. EBV, HHV-8, and HTLV-1), exposure to chemicals such as tobacco tars, genetic disorders, ionizing radiation, and a wide variety of failures of the body’s cell growth regulatory mechanisms. Different types of cancers affect different organs and have different methods of growth and harm to the body, and different vulnerabilities. Thus, it is beyond the skill of oncologists today to get an agent to be effective against cancers generally, evidence that the level of skill in this art is low relative to the difficulty of such a task.
When the best efforts have failed to achieve a goal, it is reasonable for the PTO to require evidence that such a goal has been accomplished, In re Ferens, 163 USPQ 609. The failure of skilled scientists to achieve a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art, Genentech vs Novo Nordisk, 42 USPQ2nd 1001, 1006.
Claims 1-13 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
In the claim 1, the term “ prodrug” is recited. However, the specification has not described how any prodrug or predrug is converted into its active form in the body under any circumstances. This description is essential to the claimed invention because it allows to distinguish identifying characteristics sufficient show that the applicant was in possession of the claimed invention, and the claim, as a whole, may not be adequately described where the invention is described solely in terms of a process of its conversion coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its functional language. For example, the specification merely mentions that the term “prodrug” or “predrug” refers to any compound which, upon administration to a host, is converted or metabolized to an active compound. Furthermore, Medical dictionary defines the term as a class of drugs, initially in active form, that are converted into active form in the body by normal metabolic processes. There are no examples for the class of prodrugs applicable to the claimed invention; not to mention, how the prodrugs are converted or metabolized to the active compound of the present invention.
Therefore, the specification has failed to describe the subject matter in the claims as to the relationship between the prodrugs and their final active claimed compounds during the preparation process.
Claims 1-13 are rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter that was not described in the specification in such a way to convey reasonably to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention. The issue concerning the meaning of the term “ metabolite” is discussed above. Claims 1-13 do not contain a complete generic formula.
According to the MPEP §2163 I. A. “the issue of a lack of adequate written description may arise even for an original claim when an aspect of the claimed invention has not been described with sufficient particularity such that one skilled in the art would recognize that the applicant had possession of the claimed invention. The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.” The MPEP states in §2163 II 3 ii) “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.” Applicants have disclosed no species and have made no assertion that there is any correlation between the biological function of radical “ metabolite” and its structure.
The Court of Appeals for the Federal Circuit held in University of California v. Eli Lilly and Co. 43 USPQ2d 1398 at 1406. "[a] written description of an invention involving a chemical genus, like a description of a chemical species, "requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials." In re Smythe, 480 F.2d 1376, 1383, Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . .")." Applicants' functional definitions in the claimed formula simply lack the precision required by the Court of Appeals for the Federal Circuit.
As discussed above the term “ metabolite” is not art recognized in the art of chemistry . According to the MPEP §2163.02 Standard for Determining Compliance With the Written Description Requirement,
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, “does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed". In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon “reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter". Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)).”
Thus, the chemist of ordinary skill in the art, who would use Applicants' compounds, would not know what the “ metabolite” can be for the claimed invention. That *** would not have understood the inventor to be in possession of the claimed formula (IV) or formula (IVa) at the time of filing.
This case was filed before Applicants had a clear idea of the structures of their desired compounds, how to make their compounds, and use the metabolite made from them. The specification provides broad areas of future research and speculation, inviting undue experimentation in learning how to use Applicants' invention. Applicants may well now be developing practical applications of their metabolites, but the question here is what application they possessed at the time of filing. Anything is possible but as the U.S. Patent and Trademark Office, Board of Patent Appeals and Interferences wrote in Bindra v. Kelly, 206 USPQ 570 “Probable utility does not establish practical utility. Practical utility can, in our view, be established only by actual testing therefore, or by establishing such facts as would be convincing that such utility could be "foretold with certainty.” Blicke v. Treves, supra, 112 USPQ at 475.”
Applicants are reminded of what the U.S. Court of Appeals Federal Circuit wrote in University of California v. Eli Lilly and Co. 43 USPQ2d 1398, "In claims involving chemical materials, generic formulae usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus." "A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). "It is only a definition of a useful result rather than a definition of what achieves that result." "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.")".
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)(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.
(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 14 is rejected under 35 U.S.C. 102(a)(2) as being anticipated clearly by Share (US 5,922,820)
Share discloses a compound named “Phthalic Piperazine Amide
Acid Butvl Ester in the following:
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205
451
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( see col. 16, example 1). This is identical with the claim.
Conclusion
Claims 1-14 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAYLOR V OH whose telephone number is (571)272-0689. The examiner can normally be reached 8:00-5:00.
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/TAYLOR V OH/Primary Examiner, Art Unit 1625 12/27/2025