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 NON-FINAL OFFICE ACTION is in response to the October 30, 2025 Amendment/ Request for Reconsideration After Non-Final Amendment, Rule 132 Affidavit and corresponding documents.
Claims 1, 3-4, 6-8 and 15-21 are pending and rejected, claims 1, 3-5, and 8 are currently amended, claims 6-7 are original and claims 2, 5 and 9-14 are cancelled, claims 15-21 are newly added and withdrawn by the Examiner in the above-identified application.
Priority
U.S. Pat. Appln. No. 17/794.314, Filed July 21, 2022, is a 371 Nat.’ l Stage Entry of WO2021145521A1 (i.e., PCT/KR2020/009259, Inter.’ l Filing Date: July 14, 2020, Inter.’ l Pub Date: July 22, 2021), which claims foreign priority to KR 10-2020-0005292, Filed: January 15, 2020)
WITHDRAWN REJECTIONS/OBJECTIONS
Applicants are notified that any outstanding rejection(s) or objection(s), respectively, not expressly maintained in this office action now are withdrawn or rendered moot in view of Applicants amendments and/or remarks of record.
Based on Applicants October 30, 2025 Amendment and Reconsideration After Non-Final Rejection and corresponding claim amendments, the following information is acknowledged, objections and/or rejections are withdrawn or rendered moot:
Objections of Claims 1 and 2 for claim format issues is WITHDRAWN to insert Arabic numerals (1) each chemical structure is withdrawn (i.e., see new Objections to chemical drawings)
Rejection of claim 8 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th para., as being of improper dependent form for failing to further limit the subject matter of the claim 1 upon which it depends, or for failing to include all the limitations of the claim upon which it depends (i.e., for claiming a composition that comprises a compound, but does not recite any other pharmaceutically acceptable excipients or agents, i.e., such that there is no further narrowing of the scope of the compound claim 1).
Claims 1, 3, 4 and 8 (i.e., claims 2, 5, 10 and 13) are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd para., 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 Applicants), regards as the invention:
i.e., e.g.: directed to specific rejections [a] to [d] as set forth therein, including: recitation of unclear, indefinite etc. terms “derivative”, hydrate” and/or “stereoisomer thereof”, issues re. antecedent basis, multiple inconsistent or improper Markush groups, recitation of undefined terms (i.e., “substituted functional groups” (without defining what those functional groups are substituted with), structural limitations of pharmaceutical composition that operate as intended use language and where duplicate dependent claims recite non patentable weight limitations, etc.
MAINTAINED REJECTIONS/OBJECTIONS
Maintained previous rejections of record may include:
deletion of rejections obviated by claim amendments
Amendments to the original rejections
new issues raised by amendment (i.e., in bold text as necessitated by Applicants’ arguments) and/or corresponding clarifying statements in bold text (i.e., where such. clarifying statements which do not substantively change original rejection and notes that claims 2, 5 and 9-14 now cancelled); and will be discussed in the order of significance to facilitate prosecution.
[A] MAINTAINED REJECTIONS WITH COMMENTS NECESSITATED BY AMENDMENT
[2] REJECTIONS - 35 USC 103 IS MAINTAINED
[a] APPLICANTS ARGUMENTS
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[B] EXAMINER’S RESPONSE
The arguments presented in the both the October 30, 2035 Amendment/Request for Reconsideration and Rule 132 Affidavit have been carefully considered, but are respectfully unpersuasive. The rejection(s) under 35 U.S.C. § 103 over the combination of Deng, Kannaiyan, and Yale are maintained for these reasons.
The legal standard for obviousness under 35 U.S.C. § 103, however, does not require that every limitation be expressly taught in a single reference or that the prior art provide a motivation for the exact result achieved. An invention is unpatentable if the differences between the claimed invention and the prior art as a whole would have been obvious to a person of ordinary skill in the art (POSA) at the time of the invention.
While Applicants appear to argue that the cited references must teach every element separately and that unexpected bioavailability results could not be determined from the combination, the Examiner maintains a prima facie case of obviousness is established by demonstrating a clear motivation to combine the Deng, Kannaiyan, and Yale references to arrive at the claimed invention with a reasonable expectation of success.
In summary:
Deng teaches compounds as protein kinase inhibitors and provides a basic structure:
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; or
a pharmaceutically acceptable salt thereof
X = N
Y= Phenyl
R1 is hydrogen, deuterium, C1-10 alkyl, C2-10alkenyl, C3-10cycloalkyl, 3-10 membered heterocyclyl, C5-10aryl, or 5-10 membered heteroaryl;
where:
above groups are optionally substituted with one or more substituents selected from C1-10alkyl . . 3-10 membered heterocyclyl, C5-10aryl, 5-10 membered heteroaryl. . .
R2 is hydrogen, deuterium, halogen, C1-10alkyl, C2-10alkenyl,. . . -C0-8-OR9 . . .
R3 and R4 are each independently selected from hydrogen, deuterium, halogen, hydroxy, cyano, nitro, azide, C1-10alkyl, C1-10alkoxy, C2-10alkenyl, C3-10cycloalkyl, C3-10cycloalkoxy,
3-10 membered heterocyclyl, 3-10 membered heterocyclooxy, C5-10aryl, C5-10aryloxy, 5-10 membered heteroaryl or 5-10 membered heteroaryloxy . . .,
[where] above-mentioned groups are optionally further selected from . . . . –(C0-8)-N (R11) -C (O) R10 . . . . (i.e., C0-8 equals 0, then -N (R11) -C (O) R10 ”;
[where] each R10 is . . . C5-10aryl
[where[ the above-mentioned groups are optionally further substituted with one or more . . . halogen, hydroxyl, cyano, C1-10alkyl, C1-10alkoxy . . C3-10cycloalkyl . . , 3-10 membered heterocyclic ,
C5-10aryl, C5-10aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy or -NR 11 R 12 substituents;
R5 and R6 are each independently selected from hydrogen, deuterium, … C1-10alkyl . . . .”
Kannaiyan is cited for the general knowledge of protein kinases in the art, which provides context for the intended use and common structural modifications in the field.
Yale teaches the known technique of incorporating a trifluoromethyl (CF₃) group onto an aryl ring to potentially alter physiochemical properties (e.g., solubility, metabolic stability, or bioavailability). It is a general principle in medicinal chemistry that substituting a hydrogen with a halogenated alkyl group is a common and often predictable modification, especially for optimizing known leads. The prior art provides sufficient rationale to support this conclusion.
Regarding the CF₃ substitution, the relevant question is whether an ordinary artisan at the time of the invention was made, would have been motivated to make this specific substitution with a reasonable expectation of success.
Here, Applicants state Yale is based on "simple, laboratory-scale reactions" distinguished from "modern pharmaceutical development practices"; i.e., which is unsupported argument that does not show non-enablement of the prior art.
Instead, Examiner has established CF₃ substitution is a known technique in the field of medicinal chemistry; i.e., where difficulties in synthesis yield, instability, or cost are general development challenges that do not negate prima facie obviousness of the structural modification itself.
Regarding unexpected results, Applicants present experimental results showing a high bioavailability (153.33%) as evidence of non-obviousness. While objective indicia of non-obviousness (secondary considerations) can be powerful rebuttal evidence, they must be given the appropriate weight in the overall analysis. The Examiner acknowledges the result is high.
In conclusion, the claimed compound's structure is fully taught by the combination of prior art references. The mere fact that the resulting compound exhibits a superior property does not automatically render the known compound non-obvious unless the results are unexpected or surprising, not merely an optimization of a predictable property. The prior art clearly motivates the use of CF₃ substitution to potentially improve bioavailability. While magnitude of the improvement may be higher than average, an improvement in this specific property is an expected result, making it difficult to qualify as a "surprising" or "unforeseeable" result that would overcome the strong prima facie case of structural obviousness.
Finally, persuasive bioavailability results on a single compound candidate KIST 1024 without showing a direct or side-by-side comparison with the closest prior art compounds (e.g., the non-CF₃ substituted analog from Deng) to demonstrate results are of a surprising difference in kind, not merely a difference in degree.
The references, combined with the common knowledge and predictable techniques available to a person of ordinary skill in the art, teach the claimed invention. The unexpected bioavailability argument, while noted, does not overcome the strong prima facie case of obviousness without a more robust showing, such as a comparative affidavit demonstrating truly surprising results relative to the closest prior art.
Based on the above, the rejection under 35 U.S.C. § 103 is made FINAL.
[C] REJECTION UNDER 35 U.S.C. 103 MAINTAINED REITERATED IN ITS ENTIRETY
Claims 1 to 14 are rejected under 35 U.S.C. 103 as obvious over WO 2019223766 to Abbisko Therapeutics (Inter.’l Filing Date: May 23, 2019; Inter.’l Pub. Date: November 28, 2019), alone, in view of or in combination with Yale, “The Trifluoromethyl Group in Medicinal Chemistry”, J. Med. And Pharm. Chem., Vol. 1, No. 2. (1959) at page 1, lines 8-9, and Kannaiyan et al., “A Comprehensive Review of Protein Kinase Inhibitors for Cancer Therapy:, Expert Rev Anticancer Ther. 2018 Oct 9;18(12):1249–1270.)
The present invention generally relates to a pyrido[[3,4-d]pyrimidine compounds of Formula (I):
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(I); or a pharmaceutically acceptable salt thereof,
corresponding pharmaceutical compositions, methods for making and specifically tests compounds exemplified by Formula (II) which are assayed for kinase inhibitory activity against metastasis and proliferative human cell cancer lines (i.e., e.g., which include human acutemyeloid leukemia human cell lines); and specifically exemplifies compounds with the following subgenus:
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proliferation of human acute myeloid leukemia cell lines.
WO ‘766 Appln. discloses and teaches an FGFR inhibitors having the structure of a compound of Formula (I),
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; or a pharmaceutically acceptable salt thereof
corresponding pharmaceutical compositions (i.e., also inc. stereoisomer thereof, a prodrug or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.), methods for preparation compounds applicable in the preparation of drugs, which are useful for treating tumors, cancers, myeloproliferative diseases, bone or chondrocyte disorders, and hypophosphatemia, and are expected to be developed into a new generation of FGFR inhibitor drugs.
The claimed invention is rendered obvious by the WO ‘766 Appln., (i.e., e.g., given that each and every element of the claimed compound genus and corresponding pharmaceutical composition, respectively, are encompassed and taught therein). As shown in chart below, Formula (I) of the WO ’766 Appln. directly reads on or correlates with the exemplified genus of compounds of Formula (II) of the present invention.
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While the WO ‘766 Appln. renders obvious the genus of the claimed invention and teaches R10 may be substituted with methyl, it does not teach expressly that the R10 may further substituted with a trifluoro methyl group, i.e., e.g., like the genus and compounds exemplified by the claimed invention.
However, Yale teaches it is known in the chemical arts that “trifluoro methyl group may be incorporated in the place of a methyl group” (i.e., see Yale, “The Trifluoromethyl Group in Medicinal Chemistry”, J. Med. And Pharm. Chem., Vol. 1, No. 2. (1959) at page 1, lines 8-9.
Moreover, it is noted that pharmaceutical composition claims 8-14 of the instant invention recite intended use language.
In accordance with the U.S. Patent Law, intended use limitations are typically not given any patentable weight unless some structural differences are imposed by the use or result on the structure of material recited in the claim. In general, intended use limitations are used to give context and focus the examiner's attention on the field of the invention.
Claims 8-14 of the instant invention, recite intended uses, which do appear to recite any structure limitations to Formula (I) or pharmaceutically acceptable salts thereof or corresponding pharmaceutical composition thereof. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the composition of the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim limitations, such that a statement of intended use fails to distinguish over prior art.
Pharmaceutical composition claims 8 to 14 of the claimed invention are rendered obvious by the WO ‘766 Appln., because:
a pharmaceutical composition (i.e., which comprises claimed active compounds and corresponding genus structure, respectively) are used for administration for treatment of cancer to a subject, where:
the active ingredient compound or compositions containing them, respectively, inhibit:
FGFR3 inhibitors (i.e., taught in both the WO ‘766 Appln. and identified in claim 8 of the instant invention an identified protein kinase inhibitor of the claimed invention) and
known cancers FGFR3 mutations (i.e., FGFR3 gene aberrations reported in urothelial, breast, head and neck, lung, brain, gastric, pancreatic, colorectal, kidney, endometrial, ovarian, bladder and cervical cancer); and
that many of those protein kinases were known in the conventional art at the time the invention was made (i.e., see Kannaiyan et al., “A Comprehensive Review of Protein Kinase Inhibitors for Cancer Therapy:, Expert Rev Anticancer Ther. 2018 Oct 9;18(12):1249–1270. doi: 10.1080/14737140.2018.1527688; i.e., see Table 1 at p 7-10/52 and reference generally);
recitation of intended use in claims 9, 11, 12 and 14 just recite elements that further limit cancer such that it the pharmaceutical composition is capable of being adapted for and would expect to be capable of treating cancer absent evidence to the contrary .
For example, MPEP 2112.02 states:
The claim preamble must be read in the context of the entire claim. The determination of whether preamble recitations are structural limitations or mere statements of purpose or use "can be resolved only on review of the entirety of the [record] to gain an understanding of what the inventors actually invented and intended to encompass by the claim" as drafted without importing "‘extraneous’ limitations from the specification." Corning Glass Works, 868 F.2d at 1257, 9 USPQ2d at 1966. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent).
In light of the teachings of the cited art, patent law and MPEP provisions regarding intended use the ordinary artisan would meet with a reasonable expectation of success in making and using compounds of the present invention (i.e., especially substituted with haloalkyl groups (i.e., such as CF3) conventionally used in medicinal chemistry arts for unique chemical and physiological stability as taught by Yale reference, which would entail use of corresponding pharmaceutical composition of the claimed invention for medical treatment uses against specific protein kinases and in use against specific cancer types such as acute myeloid leukemia (AML).
One of ordinary skill in the art would have been motivated to facilitate use of all compounds and corresponding pharmaceutical compositions of the present invention regardless of intended use limitations, i.e., which impart no further structural limitation advantages for use in medical treatment uses against specific protein kinases and in use against specific cancer types such as AML.
Based on the foregoing, claimed invention is rendered obvious over WO ‘766 Appln., alone, in view of or in combination with Yale, Patent Law and MPEP provisions (i.e., directed to intended use).
NEW OBJECTIONS AND/OR REJECTIONS NECESSITATED BY AMENDMENT
OBJECTIONS TO THE CLAIMS
Amended Claim 1 is objected to for claim format issues: the chemical structure of Formula (2) is unclear with variables “A” cut off defined therein.
Appropriate correction is required accordingly.
ELECTION BY ORIGINAL PRESENTATION
Newly submitted claims 15-21 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
Applicants:
constructively elected claims 1, 3, 4 and 6-8 product invention (i.e. directed to compounds and pharmaceutical compositions) by original presentation, because a first office action on the merits (FAOM) was issued for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits,
newly added method claims, being directed to a distinct and independent invention, requiring a different and separate search, are withdrawn from consideration in the instant application;
Accordingly, new claims 15-21 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
[1] REJECTION UNDER 35 USC § 112 (A) MAINTAINED AMENDED SEE [1][C] BELOW
[a] APPLICANTS ARGUMENTS TO REJECTION
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[b] EXAMINER’S RESPONSE
While incorporation of claim 2 into amended claim 1 and claim 8, respectively, has addressed some relevant issues identified issued by the Examiner (mostly pertaining to 112(b) rejections), the instant rejection has been maintained, updated and clarified as necessitated new claim amendments, where traversal arguments were found insufficient and non-persuasive in obviating outstanding enablement issues for the following reasons:
claims 15-21 directed to newly added treatment method claims were withdrawn based on election by original presentation resulting in a new ground of rejection set forth in this Final Office Action (i.e., see respective arguments that follow in this regard).;
While Applicants state that:
“representative examples together with a statement applicable to the genus as a whole will ordinarily be sufficient if one skilled in the art (i.e., in view of level of skill, state of the art and the specification information) would expect the claimed genus could be used in that manner without undue experimentation”,
the claimed invention lacks enablement due to recitation of broad scope of claimed subgenus encompassed by compounds of Formulas (2) to (9) in current amended claim 1, because:
specification Examples 1 to 26 are encompassed only by the subgenus of Formula (2), there being no representative species examples representing any compounds that fall within the scope of Formulas (3) to (9).
The Examiner disagrees with the Applicants’ assertions that:
“The specification discloses several examples of in vitro studies showing kinase inhibition and anti-proliferation activities. See Examples.
Furthermore, the specification connects kinase inhibitors to a variety of cancers. See paragraphs [0002] - [0008].
One skilled in the art would view the representative examples along with the statements in the specification for application to the whole genus of cancers with the compounds of amended claim 1.
Working examples in human subjects are not required, and the Examiner has not provided reasons for a conclusion of lack of correlation for the in vitro model examples.”
especially in light of the following explanation set forth in the last office action stating that:
Examples 1 to 26, corresponding compound intermediates and extensive written experimentals with characterization data, i.e., e.g., directed to all compounds of Formula (2), intermediates and/or processes for preparing/synthesizing each of the aforementioned compounds, etc.;
assessment of pharmacological/biological activity/efficacy via screening assays testing compounds against protein kinase inhibitory activity, inhibitory against proliferation of human acute myeloid leukemia cell lines (i.e., e.g., mt-NRAS and Ba/F3 and OCI-AM4L3), where compounds of the present invention are evaluated for potential use as therapeutic agent for acute myeloid leukemia (AML);
pharmaceutical compositions, which comprises: formulated into Tablet compositions, powder and capsule and for injection (i.e., see Exs. 1-4);
moreover, the conclusions of the 1.132 Affidavit Indicating that:
“KIST 1024 exhibits remarkable oral properties in mice, primarily 5. highlighted by its exceptional oral bioavailability of 153.33%. This high F value is highly favorable for an orally administered therapeutic, indicating that the compound is efficiently absorbed and reaches the systemic circulation in abundance, thus strongly supporting its advancement in development as a robust oral drug candidate”
does not address the broad scope of the pending claims of the present invention and lack of enablement issue as indicated.
Based on the foregoing, the lack of enablement rejection is maintained
NEW REJECTION UNDER 25 USC 112(a)
Amended claims 1, 3-4 and 6-8 (i.e., claims 2, 5 and 9-14 now cancelled), respectively are rejected under 35 U.S.C. 112(a), because the specification, while being enabling for:
pyrido[3,4-d]pyrimidine compound of Formula (2) (i.e., one specific subgenus of Formula (I)):
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; or pharmaceutically acceptable salts thereof; and
Compound Species 1 to 26, i.e., which chemical core ring structure reads on and are encompassed solely by the subgenus defined by Formula (2) as set forth in the specification;
where:
A is hydrogen, a C₁-C₁₃ alkyl group, a C₃-C₁₀ cycloalkyl group, a C₆-C₁₀ aryl group, a C₃-C₁₀ heterocyclyl group, a C₃-C₁₀ heteroaryl group, or
A together with a nitrogen atom to which R₁ is attached forms a 4- to 7-membered saturated,
where:
each A further is optionally substituted with at least one -OH, C₁-C6 alkyl group, a C₃-C₁₀ heterocyclyl group, a C₆-C₁₀ aryl, a C₃-C₁₀ heteroaryl group; and
the 4- to 7-membered saturated, optionally contains at least one of N, O, NH, ; and
B is a C₆-C₁₀ aryl group,
where:
each B further is optionally substituted with at least one - the C3-C10 heteroaryl group, or the C₃-C₁₀ heterocyclyl group, a C₁-C6 alkyl group, a C1-C₃ haloalkyl group;
where
the C₃-C₁₀ heterocyclyl group of B is optionally substituted with
a C₁-C6 alkyl group,
R₁, R₂ or R₃ each optionally are selected from hydrogen, halogen, a C1-C6 alkyl, a C1-C6 alkoxy or a C1-C6 alkenyl
corresponding pharmaceutical compositions thereof; and
DOES NOT reasonably provide enablement for:
ALL compounds of generic or subgeneric chemical Formulas (3) to (9) defined in amended claim 1;
ALL corresponding:
substituted functional groups associated with variables A, B and R1, R2, and/or R3 as defined in claim 5); and/or
pharmaceutical compositions thereof.
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:
Nature Of The Invention.
The nature of this invention relates generally to:
pyrido[3,4-d]pyrimidine derivative compound compounds of Formulas (I) (i.e., e.g., which inc.: Formulas (2) to (9) and compound species 1 to 26) or pharmaceutically acceptable salts thereof (i.e., claims 1, 3-4 and 6-8); and
corresponding pharmaceutical compositions thereof;
where assays of compounds demonstrated anti-proliferative efficacy against cancer cells.
The breadth of the claims is broad because it encompasses: in vitro and in vivo contexts in both treatment and treating diseases, i.e., as defined in the example section of the present invention, including cancer diseases or disorders with vastly different causes, progress, known or unknown etiologies or unknown etiologies or pathologies beyond those in the claimed invention.
Scope of Breath Of The Claims.
The scope of the claims involves:
pyrido[3,4-d]pyrimidine derivative compound compounds of Formulas (I) (i.e., e.g., which inc.: Formulas (II) to (IX) and compound species 1 to 26) or pharmaceutically acceptable salts thereof (i.e., claims 1, 3-4, 6-8); and
corresponding pharmaceutical compositions thereof.
Thus, the scope of claims is very broad.
3 & 4) State of the Art and Predictability In The Art.
The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification.
In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling (i.e., see MPEP 2164.03)
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.
Moreover, the convention art teaches that:
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Amount Of Guidance Provided By Applicants.
Applicants provide guidance in the detailed specification disclosure, which describes methods, procedures, and parameters for making and using compound of the claimed invention, i.e., which is primarily directed toward the how to identify and select appropriate compound: via assessment of pharmacological/biological activity/efficacy by testing or screening claimed compounds against:
protein kinase inhibitor assays against the full kinase panel shown below:
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; and
where assays were conducted:
testing compounds of the claimed invention against exemplifying acute myeloid leukemia activity, a single type of cancer type; and to
identify potential therapeutic target compounds against a variety of human cancers.
Number Of Working Examples.
[A] Working examples in the instant specification demonstrate the practicality of the claimed invention, which include detailed written description in the instant specification directed to:
Broadest Genus identified as a compound of Formula (I) or pharmaceutically acceptable salts thereof in the specification (i.e., e.g., which encompasses several subgenus of Formulas (2) to (9)); i.e., e.g., where
The subgenus of a compound of Formula (2) or pharmaceutically acceptable salts thereof, specifically encompass all compounds defined by
Examples 1 to 26, corresponding compound intermediates and extensive written experimentals with characterization data, i.e., e.g., directed to all compounds of Formula (I), intermediates and/or processes for preparing/synthesizing each of the aforementioned compounds, etc.;
assessment of pharmacological/biological activity/efficacy via screening assays testing compounds against protein kinase inhibitory activity, inhibitory against proliferation of human acute myeloid leukemia cell lines (i.e., e.g., mt-NRAS and Ba/F3 and OCI-AM4L3), where compounds of the present invention are evaluated for potential use as therapeutic agent for acute myeloid leukemia (AML)
Pharmaceutical compositions, which comprises: formulated into Tablet compositions, powder and capsule and for injection (i.e., see Exs. 1-4)
Further practical exemplification was demonstrated by excerpts shown:
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[B] Other than the limited number of in-vivo and in-vitro experimental examples in the specification, there are no working examples encompassing the broad scope or list of any of the following as set forth or defined in the instant specification, i.e., e.g.:
DOES NOT reasonably provide enablement for:
ALL compounds of generic or subgeneric chemical Formulas (3) to (9) defined in amended claim 1;
ALL corresponding:
substituted functional groups associated with variables A, B and R1, R2, and/or R3 as defined in claim 5); and/or
pharmaceutical compositions thereof.
Regarding noted above, 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. Hence, Applicants must show that the scope of claimed compounds and other requirements yields all the desired effects of scope claimed, other than those exemplified by the limited Experimental Example section of the present invention, where examples can be made/ used for the stated purpose in 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 (High)
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 in that Applicants are not enabled for compounds of Formulas (3) to (9) or pharmaceutical compositions thereof, but in the instant case the specification enables claims directed to a compound of Formula (2) or a pharmaceutically acceptable salt thereof and corresponding pharmaceutical compositions thereof. To overcome the instant rejection, Applicants are required to amend the claims to delete non-enabled subject matter directed to compounds of Formulas (3) to (9).
Appropriate action is required accordingly in the instant application.
CONCLUSION
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/G.C.H./
Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624