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 .
Status of the Claims
This is in response to the October 19, 2023 Preliminary Amendment and September 26, 2024 subsequent/miscellaneous requests.
Claims 1,4-6,10-12,15-20, 22-24
, 27-32 and 34 are pending and rejected, claims 1, 4-5, 20, 27-31 are original, claims 6,10-12,15-19, 22-24, 32 and 34 are currently amended and claims 2-3, 7-9,13-14, 21, 25-26, 33 and 35 are cancelled in the above-identified application.
Priority
U.S. Pat. Appln. No. 18/556,196, Filed: October 19, 2023 is 371 Nat.’ l Stage Entry of WO 2022/232333 A1 (i.e., PCT/US2022/026626, Inter.’ l Filing Date: April 28, 2022), which claims foreign priority to WO 2022/227015 A1 (i.e., PCT/CN2021/091534, Inter.’ l Filing Date: April 30, 2021).
Information Disclosure Statement
An Information Disclosure Statement (IDS) submitted on November 3, 2023 is in compliance with provisions of 37 CFR 1.97 and has been considered by the Examiner.
Claim Objections
Claim 16 is objected to for reciting incorrect bicyclic structures, i.e., missing carbonyl group next to NH to form an amide in Compound 354:
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Appropriate correction is required
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, 15-18 and 22-24, respectively, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd 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.
In general, the claims of the present invention fail to define the metes and bounds of the claimed invention due to use of indefinite, vague, ambiguous or unclear or poorly defined functional terms and/or language (i.e., such that exact scope of the claimed invention cannot be ascertained) without support from the specification within the claim itself. Claims must particularly point out and distinctly the claimed invention. Moreover, claims identified above also lack clarity, due to unnecessary use of repetitive and/or redundant terms.
The claim fails to provide a standard or "blaze marks" in the intrinsic evidence (specification, claims, prosecution history) that would enable a person of ordinary skill in the art to determine, with reasonable certainty, the exact boundaries of the claimed chemical structures; i.e., it’s unclear what the exact scope of the resulting chemical structure is meant to be.
[1] In particular, claim 1 is rejected for lacking clarity and for being indefinite, vague, ambiguous, because it recites multiple instances of redundant or circular sub-limitations resulting in unclear and indeterminate metes and bounds to the understanding of the ordinary artisan; i.e., following terms and issues identified and explained by letter to follow:
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With Regard To R1 and R4 Substituents
[A] For example, each R1 substituent, which is defined to include a 1st set of substituents “C1-C6 alkyl or heteroaryl (i.e., identified as “A” in the scheme above) further substitutable by a 2nd set of unsubstituted or substituted substituents selected from “C1-C6 alkyl or heteroaryl”, where 2nd “heteroaryl” substituent is further substitutable with 3rd “heteroaryl” that is “unsubstituted or substituted with C1-C6-alkoxy, yet there is no way to determine or distinguished how each substituent group (i.e., 1st to 3rd heteroaryl substituents or 1st and 2nd set of “C1-C6 alkyl), whether the pre-existing or subsequent functional group is the same or different?
Amendment to claim 1 is required to eliminate indeterminateness of the unclear definitions identified in this section.
[B] lack of clarity is associated with the phrase in box C results due separation of phrase “or R1,” (i.e., with a comma followed by “and the nitrogen to which it is attached,”) from the remainder of the phrase “is taken with R4”, which causes reader confusion:
R1 is . . . .
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The 2nd recitation of the same phrase at the end of the above paragraph makes the intended meaning apparent, however, it is recommended that each phrase preceding the alternative term “or” be separated by insertion by two semi-colons (i.e., see circled notations above) into 3 different alternate possibilities associated with the variable R4 Applicants are requested to amend claim 1 accordingly to identify above-identified reaction conditions.
[2] Claim 15 is rejected for lacking clarity and for being indefinite, vague, ambiguous, for not reciting the term “with” after the phrase “unsubstituted or substituted” and before the phrase “one or two substituents” . . . (i.e.., as shown below) which is adjectival phrase modifying the phenyl group, clarifying that each phenyl ring can exist with 0, 1, or 2 substituents.
“ wherein X is phenyl, wherein the phenyl is unsubstituted or substituted with one or two substituents independently selected from the group consisting of fluorine or bromine”.
[3] Claim 16 and 17, respectively. are rejected for lacking clarity and for being indefinite, vague, ambiguous, where the metes and bounds of the claimed invention are indeterminate, for
Claim 16 fails to particularly point out and distinctly define the claimed invention for reciting an inoperative “nitrogen containing functional group or moiety” that violates chemical valency principles, where nitrogen is known to have 3 covalent chemical bonds with a lone pair of electrons or 4 bonds with a positive charge (i.e., nitrogen in the structure below has 5 bonds attached to it):
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In claim 16 lacks clarity for not reciting the term “with” after the term phrase “unsubstituted or substituted” and before the phrase “one or two” . . . as shown below
“wherein X is unsubstituted or substituted with one or two substituents independently selected from the group consisting of fluorine and an OXO group”
[4] Claims 16, 17 and 22 recites the broad phrase “X is a Nitrogen Containing Ring" is ambiguous, vague and indefinite for same reasons set forth above in 1[D] above, except claim 16 goes on to exemplify via specific chemical structure nitrogen containing heteroaryl, bicyclic heteroaryl and fused bicyclic heterocyclic rings without explicitly defining these limitations by chemical functional group or moiety names or nomenclature, which should be expressly defined by chemical functional group nomenclature to remove any definitional ambiguity and indeterminate scope.
[5] Claim 23 is rejected for lacking clarity and for being indefinite, vague, ambiguous, where the metes and bounds of the claimed invention are indeterminate, for recitation of the following definitional phrases associated with the variable Y:
“halogen-substituted nitrogen-containing ring” or “haloC1-C6alkyl-substituted nitrogen-containing ring”, is ambiguous, vague and indefinite for same reasons set forth above in 1[D] above, except claims 22 and 23, respectively, goes on to exemplify via specific chemical structure nitrogen containing heteroaryl, bicyclic heteroaryl and fused bicyclic heterocyclic rings without explicitly defining these limitations by chemical functional group or moiety names or nomenclature, which should be expressly defined by chemical functional group nomenclature to remove any definitional ambiguity and indeterminate scope.
[6] Claim 18 is rejected for lack of clarity and for being vague and ambiguous for defining the general term cycloalkyl to include bicyclic rings, which represents inconsistent usage contrary to how these rings are defined in the chemical arts :
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While patent applicants may act as their own lexicographer, defining "C3-C6 cycloalkyl" to include bicyclic alkyl rings is technically inaccurate based on standard chemical art convention; i.e., e.g.,
cycloalkyl generally refers to monocyclic saturated hydrocarbon rings (i.e., a single saturated ring of 3 to 6 carbon atoms (cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl);
different from:
bicyclic rings refer to polycyclic systems (e.g., bicyclopentane is typically not considered "cycloalkyl" and violates standard nomenclature and structural understanding of "cycloalkyl"). Example excerpts from specification and claims appear below.
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To overcome these rejections, it is requested that Applicants amend the claims to set forth specific chemical structures defining functional group moieties for such variables R1 and X as defined in the specification and claims accordingly.
Claim Rejections - 35 USC § 112(a)
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, 4-5, 16-18, 22-24, 32 and 34 are rejected under 35 U.S.C. 112(a), because the specification, while enabling for:
[A1] Compounds of Formulas (I), (II), (III)** and (IV)** (i.e., for discussion convenience, specific embodiments identified herein by roman numerals (III)** & (IV)**, were not identified as such in the specification):
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; or
a pharmaceutically acceptable salt thereof;
where:
broad genus and/or subgenus defined in the scheme above must be defined and limited to corresponding variable and functional group definitions as supported by the specification (i.e., see chart below):
[A2] Functional Groups Associated with Formulas (I), (II), (III)** and (IV)**
Enabled Functional Groups
Not Enabled Functional Groups
L = C1-C6alkylene or C3-C6cycloalkylene linker;
L
≠
C3-C6cycloalkylene linker;
R² is H or C1-C₆alkyl;
R³ is H or C1-C6alkyl;
R⁴ is H, halogen, or C1-C₆alkyl
R² together with R³ forms a bond OR R³ together with R² forms a bond (i.e. Formula (II));
R¹ & nitrogen to which it is attached, is taken with R⁴ to forms a nitrogen-containing ring (i.e., Formula (III);
R⁴ is taken with R¹ and nitrogen to which R¹ is attached, and forms a nitrogen-containing ring (i.e., Formula (III);
R⁴ is taken with R⁵ and forms a C₃- C₆ cycloalkyl;
X
≠
All nitrogen containing rings
X is phenyl, bicyclo[1.1.1.]pentany-1-yl,
C3-C6 cycloalkyl,
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X
≠
All nitrogen containing rings
No examples of X substituted with oxo
Y is H, phenyl,
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Ex 312 Halogen substituted C1-C6 alkyl
Example 80 Y = deuterated phenyl
R1 C1-C6 alkyl (t-butyl),
Halogen substituted C1-C6 alkyl
heteroaryl (pyridinyl)
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Further sub w/C1-C6 alkyl
R1 is substituted at any position?
R1 is further substituted with
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Only 2 oxo substituted R1 rings, not enabled for oxo substitution on all R1 rings
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and
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Deuterium substitution not defined (i.e., see Example 293)Table 5 of the specification and claim last compound left bottom of chart on page 42 of 64
[A3] Enabled for exemplified by compound Examples 1 to 440; and
[B] corresponding pharmaceutical compositions of [A1] to [A3] above;
BUT DOES NOT reasonably provide enablement for:
[1] ANY or ALL compounds defined by the entire scope of a compound of Formula (I) or pharmaceutically acceptable salts thereof (i.e., as defined in claims 1, 4-5, 16-18 and 22-23);
ANY or ALL compounds of generic or subgeneric chemical Formulas (I), (II), (III)** and (IV)** defined in claims 1, 4-5, 16-18 and 22-23;
ANY or ALL corresponding:
substituted functional groups associated with variables L, X, Y and/or R1 to R5; i.e., e.g.:
the originally filed disclosure does not teach how to make and use broad scope or entire claimed range of each defined genus and/or subgenus compounds encompassed by without undue experimentation given the unpredictable chemical or pharmacological arts;
[2] ANY or ALL corresponding pharmaceutical compositions, comprised of the entire scope of a compound of Formula (I) or pharmaceutically acceptable salts thereof (i.e., as defined in claim 34); and
[3] ANY or ALL methods for treating ANY or ALL cancer disease(s), which comprises: administering a compound or a pharmaceutically acceptable salt thereof of claim 1 (i.e., as in claim 32) ;
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 the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation. (United States v. Teletronics Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based on a single factor, but rather a conclusion reached by weighing many factors (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
These factors include the following:
Scope Of The Claims
The scope and nature of the claims and invention involves:
The present invention relates to compounds of Formula I:
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;or a pharmaceutically acceptable salt thereof.
The compounds of Formula I act as IL4I1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for IL4I1-related diseases, such as cancers.
Thus, the scope of claims is very broad.
The Nature Of The Invention and 3) Predictability In The Art.
The invention is directed toward medicine and is therefore physiological in nature. 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).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Number Of Working Examples and 5) Amount Of Guidance Provided By Applicants.
Working examples in the instant specification are directed to
[A] Compound Examples 1-440 A-D, which describe compounds, corresponding Intermediate Examples 1-180 and methods of making or preparing, also as identified in Scheme 1 to 25.
[B] Compound Screening against IL4I1Assay defined in specification which assess inhibitory effect and potency (EC50) on IL4I1 of compound Examples 1-440 A-D measure by effectiveness of the aforementioned compounds to inhibit H2O2 production
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[C] While the specification:
provides information directed to 440 compounds examples, corresponding intermediates, synthetic methods of making those compounds and determination of in vitro potency (EC50) data associated with enzymatic activity associated with each compound; i.e., where:
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;
but there are NO in vitro or in vivo assays testing any of the compound derivatives of the claimed invention demonstrating any potential or actual IL4I1 activity, inhibition, and/or used in prevention, treatment or action as a remedial agent for IL4I1-related diseases, effective against any types of cancers.
Regarding that described above, identification additional compounds, stereoisomers, etc. that may be useful for general cancer diseases or disorders 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. Hence, Applicants must demonstrate that specific cancers, associated with IL4I1 activity, inhibition may be used in prevention, treatment or action as a remedial agent for IL4I1-related diseases and provide corresponding data and other requirements yields all the desired effects of the claimed invention, other preliminary inhibition or potency data that does not indicate claimed compound examples are effective and used for the stated purpose in treatment of specific cancers (i.e., as defined in the specification) which may include all situations across the board, not just in animals, but also in human subjects or limit the claims accordingly.
Level Of Skill In The Art.
An ordinary artisan in the area of drug development would have experience in screening chemical compounds for particular activities. Screening of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target, (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can often be employed, developing a therapeutic method, as claimed, is generally not well-known or routine, given the complexity of certain biological systems.
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 that Applicants are not enabled for using broad scope of derivatives of Formula (I) or pharmaceutically acceptable salt or stereoisomers thereof or corresponding pharmaceutical compositions, or treating any cancer disease or disorder; i.e., e.g.,
a person of ordinary skill in the art would have to engage in undue experimentation to identify all possible derivatives, stereoisomers, cancer diseases or conditions that meet this complex description without explicit guidance or representative examples in the specification.
"The specification does not teach how to treat all claimed conditions": The phrase covers a potentially vast number of different cancers and the specification does not provide sufficient data or teaching to show the claimed method works across the entire breadth of these diseases/conditions.
there are NO Examples, prophetic or otherwise, that are credible to enable a skilled person to practice the invention without undue experimentation for treatment of any cancers to satisfy the enablement requirement.
Based on the above, Applicants are requested to review:
the scope of the claimed invention in view representative Examples 1-440;
amend the claims to be commensurate in scope with the enabled compounds or pharmaceutically acceptable salts thereof; i.e., e.g.:
incorporate specific compound species identified in the specification and not found in the prior art; incorporation of claims 5, 15, 16, 20, 22-24, further in consideration of Chart [A2] and all comments herein) into amended claim 1 to overcome relevant issues identified in this outstanding office action; and
provide supporting data via a 37 CFR 1.132 Affidavit showing Any or ALL supportive data to show the nexus between activity associated with IL4I1 activity EC50 potency data/inhibitory effect of compound examples of the present invention are evaluated for potential use as therapeutic agent for treatment of specific cancers; i.e., e.g., as defined at page of the specification of the claimed invention:
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Appropriate action is required accordingly in the instant application.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
The Present Invention As Applied to Prior Art
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[1] Claims 1, 6, 10-11, 15, 32 and 34 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Hori et al: Chemical and Pharmaceutical Bulletin, Pharmaceutical Society of Japan, Vol. 29, No. 3, 1 January 1981, pp. 684-698 (“Hori I”)
Hori I teaches and discloses antitumor-active 2,3-dioxopiperazine derivatives, which are cytotoxic agents, and corresponding structure activity relationships and that the aforementioned compounds showed invitro cytotoxicity or effects of compounds, which include compounds 12a, 12b and 12j-12m (Table III) therein that fall under the scope of Formula I of present claim 1., where a pharmaceutical composition (i.e., culture solutions or suspensions taught, where test compound(s) added to a solution, saline or culture medium, i.e., see page 690) was tested for antitumor activity against Ehrlich ascites carcinoma (i.e., see pp. 687, Experimental section to page 691, lines 1-21).
HORI I REFERENCE
Read on Formula (I) of claimed invention
[AltContent: textbox (C6H13 = n-Hexyl )]
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R1= Hexyl= C6H13
R2 to R5 = H
L = CH2
X = methoxy sub. phenyl
Y = H
Therefore, the Hori I reference anticipates the claimed invention.
[2] Claims 1, 6, 10-11, 15, 22, 32 and 34 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Hori et al, Chemical and Pharmaceutical Bulletin, Pharmaceutical Society of Japan, Vol. 29, No. 5, 1 Jan 1981, pp 1253-1266 (“Hori II”)
Hori II teaches and discloses antitumor-active 2,3-dioxopiperazine derivatives, which are cytotoxic agents, and corresponding structure activity relationships and that the aforementioned compounds showed in vitro and in vivo cytotoxicity or effects of compounds, which include compounds 11a and 11i (Table II) that fall under the scope of Formula I of present claim 1 therein, where a pharmaceutical composition (i.e., culture solutions or suspensions taught, where test compound(s) added to a solution, saline or culture medium, i.e., see page 690) was tested for toxicity in mice, antitumor activity against Ehrlich ascites carcinoma and L1210 mouse leukemia cell line (i.e., pp. 1265, Experimental section (14 lines from page bottom) to page 1266, lines 1-9).
HORI II REFERENCE
Read on Formula (I) of claimed invention
[AltContent: textbox (C6H13 = n-Hexyl )]
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R1= Hexyl = C6H13
R2 to R5 = H
L = CH2
X = methoxy sub. phenyl
Y = nitrogen containing ring
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Therefore, the Hori II reference anticipates the claimed invention.
[3] Claims 1, 6, 10-11, 15, 22, 32 and 34 are rejected under 35 U.S.C. 102(a)(1) as anticipated by WO 2010/125103 A1 to Glaxo Group Ltd [Gb] (Intern.’l Filing Date: April 28, 2010, Intern.’l Pub. Date: 4 November 2010; “WO ‘103 Appln.”).
In general, WO ‘103 Appln. teaches and discloses a compound of Formula (I):
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; or a pharmaceutically acceptable salt thereof:
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WO ‘103 Appln. discloses:
compounds of Examples 3-6, 8, 12-13, 15-19, 21-22, 24, 27-29, 34-36, 38, 40-45, 47-48, 55-57, 83-87, 89-92, 94, 96, 99-105, 108, 112, 114-123 and 125-126 (i.e., which may or may not be identified with label “E”) which read on Formula I of the claimed invention;
representative compounds from the WO ‘103 Appln. are shown below:
Example
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R1= as defined in claim 1
R2 to R5 = H
L = CH2
X = as defined in claim 1
Y = H
E55
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E6
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E56
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E15
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E24
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125
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corresponding pharmaceutical compositions thereof; and
where the aforementioned compounds or pharmaceutically acceptable salts therein \ modulate P2X7 receptor function and are capable of antagonizing the effects of ATP at the P2X7 receptor ("P2X7 receptor antagonists"); which may be useful in the treatment or prophylaxis . . . use in pain associated with cancer and cancer chemotherapy.
Therefore, the WO ‘103 Appln. reference anticipates the claimed invention.
[4] Claims 1, 6, 10-11, 15, 22, 32 and 34 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Dolfen et al., Chemistry - A European Journal, vol. 22, no. 14, 24 March 2016, pages 4945-4951.
In general, Dolfen teaches a synthetic preparative methodology for making diketopiperazines.
In particular, the above-identified references teaches compounds 6a, 6b and 6c in Table 3 of document D7 fall under the scope of formula I of present claim 1.
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Therefore, the Dolfen reference anticipates the claimed invention.
[5] Claims 1, 6, 10-11, 15, 22, 32 and 34 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Hussein et al., Bulletin Of The Korean Chemical Society, Vol. 32, No. 5, 20 May 2011, Pages 1511-1518 (“Hussein I”).
Hussein I teaches and discloses 1,4-Disubstituted Octahydroquinoxaline-2,3-dione compounds and corresponding pharmaceutical compositions thereof (i.e., used to test compounds for identified biological activity assessed therein)
In particular, the Hussein reference discloses compounds 2a-2d and 2i, which read on Formula I of present claim 1 and corresponding pharmaceutical compositions thereof.
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Therefore, the Hussein I reference anticipates the claimed invention.
[6] Claims 1,6,10-11,15, 22, 32 and 34 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Chamorro-Arenas et al., The Journal of Organic Chemistry, Vol. 83, No. 24, 21 December 2018, pp. 15333-15346 (“Chamorro-Arenas”)
In general, Chamorro-Arenas teaches and discloses a novel protocol for the direct functionalization of piperazines to 2,3-diketopiperazines under transition-metal-free conditions, using environmentally friendly reagents’
In particular, this reference teaches the following compounds 12 (in Table 1) and 14a, 14b, 14g, 14i and 14p (in Table 2), which all fall under the scope of Formula I of the claimed invention:
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124
72
media_image39.png
Greyscale
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media_image40.png
7
3
media_image40.png
Greyscale
PNG
media_image40.png
7
3
media_image40.png
Greyscale
PNG
media_image40.png
7
3
media_image40.png
Greyscale
PNG
media_image40.png
7
3
media_image40.png
Greyscale
Therefore, the Chamorro-Arenas reference anticipates the claimed invention.
[7] Claims 1, 6, 10-11, 15, 22, 32 and 34 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Hussein et al., Bulletin of Pharma. Sciences. Assiut, Vol. 28, No. 1, 1 June 2005, pp. 37-44.
Hussein teaches and discloses compounds 2a-2g in Table 2 which read on Formula I of claim 1.
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520
482
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Greyscale
Therefore, the Hussein reference anticipates the claimed invention.
[8] Claims 1, 6, 10-11, 15, 22, 32 and 34 are rejected under 35 U.S.C. 102(a)(1) as anticipated by GB 2 056 976 A to Toyama Chemical Co Ltd, 25 March 1981 (“Toyama”).
In general, Toyama teaches and discloses 1-(4-aminobenzyi)-2,3-dioxopiperazine derivatives that encompass compounds of the present invention:
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492
685
media_image42.png
Greyscale
In particular, Toyoma discloses:
compound 31 (cf page 10), the compound on page 59 each of which fall under the scope of Formula I of the claimed invention:
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media_image43.png
86
867
media_image43.png
Greyscale
PNG
media_image44.png
119
863
media_image44.png
Greyscale
; and
pharmaceutical composition, i.e., solutions or suspensions tested in mice where effects were evaluation for anti-cancer activity by testing against Ehrlich carcinoma cells (cf page 30, lines 33-37)
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120
587
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Greyscale
Therefore, Toyoma anticipates the claimed invention.
Conclusion
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/G.C.H./
Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624