DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-8 are examined herein.
Claims 9-15 are withdrawn (see restriction/election below).
Priority
This application is filed 11/03/2023 and no claims the benefit of domestic priority.
Information Disclosure Statements
Four references from IDS(s) received on 1/25/2024, 4/02/2024, 6/28/2024, and 6/16/2025 have been considered unless marked with a strikethrough.
Election/Restrictions
Applicant elects Group I, claims 1-8, and 14-15, drawn a method of treating cancer by administering a compound of Formula I or combination with an anticancer drug, with traverse in the reply field on 03/02/2026 is acknowledged.
However, claims 14-15 are incorrectly placed in the method of use group (e.g., Group I) and should have been placed in the product claim group (e.g., Group II). This error is corrected herein as follows:
Group I. Claims 1-8, are drawn to method of treating cancer by administering a compound of Formula I or combination with an anticancer drug.
Group II. Claims 9-15, are drawn to a pharmaceutical composition comprising a compound of Formula I or a pharmaceutically acceptable salt thereof.
In view of this correction, the restriction requirement is not made final in this Office Action to allow Applicants an opportunity to respond to the revised grouping.
Accordingly, non-elected Group II, claims 9-15, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method of use, there being no allowable generic or linking claim.
The applicants argue that the restriction is improper because it is not based on the specific language of the claims and instead relies on hypothetical situations not recited in the claims. In particular, Applicants asserts that the claims neither recite the use of a different product nor any alternative use, and therefore the Examiner has disregarded the specific language of the claims.
The Examiner maintains that restriction requirement for the following reasons. The instant application included inventions that are properly divisible under 35 USC § 121 into Group I (i.e., method of treating cancer), classified in CPC A61K45/06, and Group II (i.e., pharmaceutical composition), classified in CPC C07D215/12. These groups are related as a product and a process of use. Under MPEP 806.05(h), such inventions may be considered independent or distinct if (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process. In the present case, even though the same compound is recited, the inventions are directed to different statutory categories and different inventive aspects, a pharmaceutical composition per se versus a specific therapeutic method for enhancing sensitivity to an anticancer drug. These differences in inventive focus are sufficient to render the inventions distinct.
Moreover, claim interpretation must be conducted under the broadest reasonable interpretation (BRI) standard. (see MPEP 2111) The standard does not limit the analysis to narrow or purely literal reading of isolated claim terms, but rather requires interpretation consistent with how one of ordinary skill in the art would reasonably understand the claimed subject matter. The Examiner has not disregarded the claim language. Instead, the Examiner has properly considered the distinct inventive focus of the claimed subject matter in determining that the inventions are distinct.
Lastly, the two groups fall into different fields of technology, as reflected by their respective CPC classifications. Group I is classification in A61K45/06, which pertains to mixtures of active ingredients without chemical characterization of medicinal preparations characterized by the non-active ingredients used, while Group II is classification in C07D215/12, which pertains to the substituted hydrocarbon radicals attached to ring carbon atoms of heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems. This difference indicates that the inventions have acquired a separate status in the art and require different fields of search. Specifically, examination of Group I requires searching prior art related to methods of treatment, enhancement of drug sensitivity, combination therapies, and biological response mechanisms. In contrast, examination of Group II requires searching prior art directed to chemical structures, synthesis, salts, and pharmaceutical formulations of the claimed compound, typically involving chemical structure databases and organic chemistry literature. These differences necessitate distinct search strategies, search queries, and technical resources. Accordingly, examining the inventions together would result in a serious search and examination burden. Therefore, in view of the difference in statutory class, incentive focus, CPC classification, and required fields of search, the restriction requirement is deemed proper.
Applicant elects thyroid cancer as the species of cancer. Applicant further elects the species of a combination comprising lenvatinib or sorafenib as an anticancer drug and Formula 2 or Formula 3 as an active ingredient, without traverse in the reply field on 03/02/2026 is acknowledged.
Claims 1-8 read on the elected species and will be examined on their merits.
If the elected specie is not identified in the prior arts, the elected specie would be allowable if an independent claim were drafted with that specie alone, and Examiner expanded the search to additional species of the genus per MPEP 802.03.
With respect to the elected species, the art is rejected under 35 USC 112 and 103 below.
Claim interpretation
Claims are interpreted in accordance with the broadest reasonable interpretation (BRI) standard
consistent with the specification (See MPEP 2111).
With respect to claim 6, the term “food” is a broad and undefined term and the claim does not clearly specify the nature or scope of the “food” with which the pharmaceutical composition is combined. Therefore, the meaning and boundaries of limitation “administered in combination with a food” is interpreted to encompass administration of the claimed pharmaceutical composition together with any such ingestible substance.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because:
The lines, numbers and lettering are not clean, well-defined, sufficiently dense and dark, and uniformly thick and well defined in Figure(s) 1c 2b, 3a-e, 4a-e, and 6a-e. See 37 CFR 1.84(l) and (q). The graphs, in particular, have significant overlap, making them difficult to interpret.
Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112, Written Description
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 1-8 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by applicants. (see MPEP 2163.02)
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. (Emphasis added)
Further, the MPEP states that for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. (see MPEP 2161.01)
For instance, generic claim language in the original disclosure does not satisfy the written description requirement if it fails to support the scope of the genus claimed. Ariad, 598 F.3d at 1349-50, 94 USPQ2d at 1171 ("[A]n adequate written description of a claimed genus requires more than a generic statement of an invention’s boundaries.") (citing Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1405-06); Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002) (holding that generic claim language appearing in ipsis verbis in the original specification did not satisfy the written description requirement because it failed to support the scope of the genus claimed); Fiers v. Revel, 984 F.2d 1164, 1170, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (rejecting the argument that "only similar language in the specification or original claims is necessary to satisfy the written description requirement").
As set forth in the en banc decision in Ariad Pharmaceuticals Inc. v. Eli Lilly and Company, 94 USPQ2d 1161 (Fed. Cir. 2010) at 1171, the court stated as follows:
We held that a sufficient description of a genus instead requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can “visualize or recognize” the members of the genus. Id. At 1568-69. We explained that an adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials. Id. At 1568 (quoting Fiers v. Revel, 984 F.2d 1164, 1171 [25 USPQ2d 1601] (Fed. Cir. 1993)). We have also held that functional claim language can meet the written description requirement when the art has established a correlation between structure and function. See Enzo, 323 F.3d at 964 (quoting 66 Fed. Reg. 1099 (Jan. 5, 2001)). But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species.
With respect to claims 1-8, the claims are drawn to a method for enhancing sensitivity of cancer to anticancer drugs in a subject by administering a pharmaceutical composition containing an active ingredient a compound represented by the following Formula 1 or a pharmaceutically acceptable salt thereof. Claim 1 encompasses a broad method of enhancing sensitivity of cancer to anticancer drugs without limitation to specific cancer types or therapeutic contexts. Claim 2, although narrowing the Markush structure of claim 1 to a subset of compounds, still encompasses a structurally diverse genus and does not limit the claimed method with respect to specific cancer types, therapeutic context, or class of anticancer agents. Further, the narrowed subset of compounds in claim 2 is not associated with any disclosed the relationship between structure and function that would meaningfully reduce unpredictability in sensitization across different anticancer agents or cancer types. Claim 3 encompasses a wide variety of cancers, including resistant, recurrent, or metastatic cancers and numerous specific cancer types across multiple organ systems. Claims 4-8, further encompass that the anticancer drug used in combination with the claimed compound is selected from an extensive list of therapeutic agents and a food. The recited agents encompass a broad genus of anticancer drugs spanning multiple fundamentally distinct therapeutic class, including kinase inhibitors, monoclonal antibodies, cytotoxic chemotherapeutic agents, hormonal therapies, immunotherapeutic agents, and antimetabolites.
In the field of cancer therapy, particular drug resistance and sensitization, is well recognized as highly unpredictable and heterogeneous. As described by Holohan et. al. (Cancer drug resistance: an evolving paradigm, Nature Review Cancer, 13(10), 714-726, pub’d 09/24/2013), mechanisms of cancer drug resistance and sensitization are broad, including drug efflux, DNA repair, apoptosis evasion, and tumor microenvironment effect, and that these mechanisms differ depending on tumor type and treatment (Key points, and table 1 and 2). Similarly, Shlyakhtina et. al. (Genetic and Non-Genetic Mechanisms Underlying Cancer Evolution, Cancer, 13, 1380, pub’d 03/18/2021) demonstrates that resistance arises through diverse genetic and non-genetic mechanisms and evolve dynamically during treatment, making therapeutic responses difficult to predict across different drug and cancer types (simple summary section, and Figure 3).
In view of these teachings, the art would not reasonably expect that the possession of a given compound to enhance sensitivity to an anticancer drug could be reliably extrapolated across different classes of anticancer agents or cancer types. This unpredictability is further heightened in the instant application because the anticancer drugs are encompassed by the claims (e.g., claims 5, and 8) include kinase inhibitors, cytotoxic agents, antimetabolites, and immunomodulatory agents. Given the mechanisms of action and resistance pathways associated with these classes, there is no reasonable expectation that a single sensitizing compound including claims 1 and 2 would uniformly enhance efficacy across such a broad range of therapies.
The instant specification states that “In one example of the present invention, it was confirmed that, when the compound represented by Formula 1 was administered in combination with a tyrosine kinase inhibitor, particularly sorafenib or lenvatinib, which is a kind of anticancer drug, it could effectively enhance the activity of the anticancer drug in drug- resistant, recurrent or metastatic cancer, thereby very effectively reducing the size and weight of tumors” (paragraph [0036]). The specification provide limited experimental data demonstrate co-administration between CKP1/2 and lenvatinib, or sorafenib (Figure 4 and 5). However, the specification does not provide supporting experimental data demonstrate co-administration including evidence of synergy effects, and dosing compatibility, or therapeutic interaction between compounds of Formula (I) or the narrower subset of claim 2, and the wide variety of claimed anticancer agents/cancer types. Accordingly, the specification does not reasonably convey that the inventors are in possession of which specific combinations of compounds of Formula (I) and anticancer agents/foods would result in enhanced sensitivity. The absence of such data further reflects that the inventors are not in possession of the claimed combinations at the time of filing.
In addition, although lenvatinib and sorafenib are specifically mentioned, the claims encompass a significantly broader genus of combination therapies. In particular, claims 3-5, 7 and 8 include anticancer agents spanning multiple fundamentally distinct therapeutic class, including kinase inhibitors, monoclonal antibodies, cytotoxic chemotherapeutic agents, hormonal therapies, immunotherapeutic agents, and antimetabolites. Further, claim 6 includes administration in combination with an anticancer drug to enhance an activity of the anticancer drug with a food without limitations to specific food type. In view of the extensive number of district therapeutic classes encompassed by the claims, the claimed subject matter includes a wide range of structurally and mechanistically diverse combinations. However, the specification fails to provide a representative number of species across the full scope of those combinations, and does not provide structural or mechanistic guidance that would allow one of ordinary skill in the art to reasonably predict which combinations would exhibit the claimed sensitization effect. This deficiency applies equally to claims 1 and 2, as the scope of compounds of Formula (I) or the narrower compounds, do not correspond to any identified compounds for which predictability has been established. Therefore, the specification does not demonstrate possession of the full scope of the claimed genus of combination therapies.
As evidenced by Holohan and Shlyakhtina, cancer drug response and sensitization mechanisms are highly unpredictable, varying across tumor types, therapeutic classes, and treatment contexts. In view of such unpredictability and the lack of any disclosed structure function or mechanism based correlation, a person of ordinary skill in the art would not recognize that the inventors had possession of which combinations of cancer types, compounds of Formula (I), anticancer agents, and foods would achieve the claimed sensitization effect at the time of filing.
As set forth in the en banc decision in Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010), to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention at the time of filing. Specifically, the specification must describe the claimed invention in a manner understandable to a person of ordinary skill in the art in a way that shows that the inventor actually invented the claimed invention at the time of filing. Id.; Ariad, 598 F.3d at 1351, 94 USPQ2d at 1172. (see MPEP 2161.01).
Accordingly, in view of the breadth of the claimed combinations, the lack of representative examples, and the unpredictability of the art as discussed above, the specification does not reasonably convey to those skilled in the art that the inventors are in possession of the full scope of claimed combination therapies at the time of filing.
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.
The rejections under this section are made when the scope of the claimed subject matter is not clear. (See MPEP 2173)
Claim 3 is 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 3, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Accordingly, claim 3 is rendered indefinite.
Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
The present rejection under 35 U.S.C. 103 is directed to the co-administration of CKP1/2 with lenvatinib or sorafenib. This rejection applies to a method for enhancing sensitivity of a subject to an anticancer drug, comprising administering to the subject a pharmaceutical composition by Formular (I) in combination with lenvatinib or sorafenib.
Claim(s) 1-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Daeuble et. al. (US 6117884, pub’d 09/12/2000), in view of Courcambeck et. al. (US 10,179,770 B2, pub’d 01/15/2019), and in further view of Li et. al. (WO 2022/032223 Al, pub’d 02/10/2022).
With respect to independent claim 1, the claim recites that a method for enhancing sensitivity of a subject to an anticancer drug, comprising administering to the subject a pharmaceutical composition containing as an active ingredient a compound represented by the following Formula 1 or a pharmaceutically acceptable salt thereof.
Daeuble teaches 4-substituted quinoline derivatives including styryl quinoline derivatives encompassed by Formula 1. Daeuble’s formula (1) has R1, R2, and R3 are hydrogen, R4 is CH3, X is CR5, R5 is CH3, V is C1 alkenyl, Z is N, A is a phenyl with a halogen in para position (column 1 lines 14 - column 2 line 10). Daeuble further teaches specific styryl quinoline compounds, including the exemplified compound (e.g., compound 55, column 19), which represent preferred embodiments of the disclosed quinoline genus. The Cl substituents at R1 and R3 position in compound 55 are indicated as being replaceable with hydrogen in the specification (column 1 lines 14 - column 2 line 10).
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Daeuble’s formula (1) Instant application Compound 55 (Daeuble)
Daeuble fails to teach a method for enhancing sensitivity of a subject to an anticancer drug.
Courcambeck teaches quinoline derivatives useful as anticancer agents and pharmaceutical compositions comprising quinoline based compounds for the treatment of cancer (column 1 lines 34-48). Courcambeck further teaches that quinoline derivatives inhibit proliferation of tumor cells and are useful for treating a variety of cancer (abstract, claims 25-26). Thus, Courcambeck establishes that quinoline based compounds are biologically active in oncology and provide therapeutic benefit through inhibition of tumor growth. Accordingly, Courcambeck provides motivation to use quinoline based compounds, such as those disclosed in Daeuble, in cancer related therapeutic applications.
The combination of Daeuble and Courcambeck fail to teach methods of sensitizing cancer cells to anticancer therapy using small sensitizing agents in combination with chemotherapeutic drugs.
Li teaches that administration of small quinazolines sensitizing agents in combination with chemotherapeutic drugs increases tumor cell susceptibility and improve therapeutic efficacy (page 13, lines 19-23, page 30 line 22- page 31 line 6, page 33 lines 20-25, claims 1, and 2). Li further indicates that such sensitizing agents can include biologically active small molecules capable of modulating cancer cell response, thereby providing improved treatment outcomes though enhanced drug sensitivity (page 12 lines 14-28, example 17, page 47 lines 3-19, and page 28 line 23-page 29 line 15). Accordingly, Li does not limit sensitizing agents to a specific structural class, but broadly teaches the use of biologically active small molecules, including heterocyclic compounds, to enhance anticancer drug efficacy.
It would have been obvious to a PHOSITA at the time of the invention to combine the styryl quinoline compounds disclosed in the Daeuble in combination with the quinoline derivatives useful as anticancer agents and pharmaceutical compositions taught by Courcambeck, and methods of sensitizing cancer cells to anticancer therapy using small quinazolines sensitizing agents in combination with chemotherapeutic drugs, taught by Li. It would be reasonably expected that quinoline structured compounds already known to anticancer activity taught by Courcambeck, can be used in combination with chemotherapeutic agents to enhance cancer cell sensitivity and thereby improve therapeutic efficacy, as taught by Li. For example, Courcambeck teaches quinoline derivatives having anticancer activity against tumor cells, and Li teaches that small quinazolines enhance the effectiveness of anticancer drugs by increasing tumor cell susceptibility. Accordingly, combining the quinoline compounds of Daeuble with anticancer drugs would have predictably resulted in enhanced anticancer efficacy through increased sensitivity of cancer treatment.
The references is directed to the same field of endeavor and address related to the application. The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying KSR example rationale (A) in the independent claim 1, it would have been prima facie obvious to combine quinoline compounds known to exhibit anticancer activity with methods known to enhance sensitivity of cancer cells to chemotherapeutic agents represents the predictable use of known elements according to their established functions, yielding predictable results. (see MPEP 2141)
With respect to claim 2, the claim recites that the method according to the claim 1, wherein A is -CH; B is N; R1 and R2 are each independently C1 to C3 alkyl; and X is halogen, or wherein A is N; B is -CH; R1 and R2 are each independently selected from the group consisting of C1 to C3 alkyl; and X is halogen.
Daeuble teaches formula (1) has R1, R2, and R3 are hydrogen, R4 is CH3, X is CR5, R5 is CH3, V is C1 alkenyl, Z is N, A is a phenyl with a halogen in para position (column 1 lines 14 - column 2 line 10), and it falls within the scope of the instant claimed compounds. For example, Daeuble teaches specific quinoline compounds showed in compound 55, which represent preferred species within the disclosed genus of Formula (1). Daeuble discloses compounds having substituents including the Cl substituents at R1 and R3 position in compound 55 are indicated as being replaceable with hydrogen and R4 and X are indicated as being replaceable with CH3 in the specification, that is corresponding to the structural limitation recited in the instant claim 2 (column 1 lines 14 - column 2 line 10).
Daeuble teaches all structural element variation of claim 2 within the explicitly disclosed substituent options. Daeuble further discloses a finite set of substituents for each variable position, thereby providing a limited number of predictable variations.
Applying KSR example rationale (A) and (E), it would have been prima facie obvious to select the specific quinoline compound of the claim 2 from the finite number of identified. Predictable quinoline derivatives disclosed by Daeuble and use such compound in combination with anticancer drugs to enhance sensitivity disclosed by Courcambeck and Li, as discussed above with respect to independence claim 1. A person having ordinary skill in the art would have reasonably expected that the selected quinoline compound already known in the art, would exhibit similar biological activity and provide predictable results in enhancing anticancer drug efficacy in view of Courcambeck and Li. (see MPEP 2141)
With respect to claim 3, the claim recites that the cancer is resistant, recurrent or metastatic cancer, and includes numerous specific cancer types.
As discussed above with respect to independence claim 1, Courcambeck teaches that quinoline derivatives having anticancer activity and usefulness in treating a variety of cancers, including thyroid cancer, which correspond to the cancer types recited in the instant claim 3 (claims 26-29).
Applying KSR example rationale (A), it would have been prima facie obvious to select particular cancer type from among known cancers treatable with quinoline based anticancer compounds represents the predictable application of a known therapeutic agent to disease already recognized in the art, yielding predictable results. (see MPEP 2141)
With respect to claims 4 and 5, the claims recite that the compound is administered in combination with the anticancer drug to enhance an activity of the anticancer drug, and includes numerous specific cancer drugs.
Courcambeck teaches administering agents in combination with anticancer drugs (i.e., anti-neoplastic agents) included sorafenib in order to enhance the therapeutic effectiveness of chemotherapy, corresponding to the co-administration limitations recited in the instant claims 4 and 5 (claim 22, 23, 25, column 23 line 31- column 24 line 67, and examples 58-60). Li further teaches that co-administration of small molecule sensitizing agents with chemotherapeutic drugs for enhancing therapeutic efficacy.
Applying KSR example rationale (A), it would have been prima facie obvious to combine the quinone compounds disclosed by Daeuble with known chemotherapeutic agents as taught to Courcambeck, and apply the sensitization strategy taught by Li, thereby improve treatment outcome, yielding predictable results. (see MPEP 2141)
Claims 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Daeuble et. al. (US 6117884, pub’d 09/12/2000), in view of Courcambeck et. al. (US 10,179,770 B2, pub’d 01/15/2019) and Li et. al. (WO 2022/032223 Al, pub’d 02/10/2022), and in further view of U.S. Food and Drug Administration (FDA, Food-Effect Bioavailability and Fed Bioequivalence Studies: Guidance for Industry, https://www.fda.gov/files/drugs/published/Food-Effect-Bioavailability-and-Fed-Bioequivalence-Studies.pdf, pub’d 12/2002, herein “FDA”)
The combination teaches as disclosed above and at least those teachings are incorporated by reference herein.
The combination fails to teach the pharmaceutical composition is administered in combination with a food.
With respect to claim 6, the claim recites that “the pharmaceutical composition is administered in combination with a food.”
FDA establishes that evaluating the effect of food on drug absorption is a routine and standard part of drug development. Specifically, FDA explains that food effect studies are typically conducted for orally administrated drugs to assess the impact of food on bioavailability, and such assessments are part of conventional pharmacokinetic optimization (recommendations for food-effect BA and Fed be studies section, and test meal section).
In addition, MPEP 2112.01 states that “In King Pharma, the court found that the relevant determination is whether the "instruction limitation" has a "new and unobvious functional relationship" with the known method of administering the drug with food. Id. The court held that the relationship was non-functional because "[i]nforming a patient about the benefits of a drug in no way transforms the process of taking the drug with food." Id. That is, the actual method of taking a drug with food is the same regardless of whether the patient is informed of the benefits. Id. "In other words, the ‘informing’ limitation ‘in no way depends on the method, and the method does not depend on the ‘informing’ limitation.’" Id. (citing In re Ngai, 367 F.3d 1336, 1339 (Fed. Cir. 2004)); see also In re Kao, 639 F.3d 1057, 1072-73, 98 USPQ2d 1799, 1811-12 (Fed. Cir. 2011).”
It would have been obvious to a PHOSITA at the time of the invention to administer drug with food, as food co-administration represents a well-known and routinely evaluated variable affecting drug performance. Further, under the broadest reasonable interpretation of “food”, co-administration with ingestible substances reflects a conventional condition of use evaluated during drug development, rather than a distinct or inventive step. Accordingly, the claimed limitation of administering the compound with food does not impart patentable distinction, as it merely reflects routine and predictable optimization of known administration parameters. The claimed subject matter is obvious, and yielded predictable results. (see MPEP 2144.05)
With respect to claims 7 and 8, the claims recite that the compound is administered in combination with food, the anticancer drug to enhance an activity of the anticancer drug, and includes numerous specific cancer drugs.
As discussed above with respect to claim 6, FDA establishes that evaluating the effect of food on drug absorption is a routine and standard part of drug development. FDA further explains that food effect studies are typically part of conventional pharmacokinetic optimization.
Applying KSR example rationale (A), it would have been prima facie obvious to combine the quinone compounds disclosed by Daeuble with known chemotherapeutic agents as taught to Courcambeck, and apply the sensitization strategy taught by Li with routine and predictable optimization of known administration parameters for foods, yielding predictable results. (see MPEP 2141)
Conclusion
Claims 1-8 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEONG JONG KIM whose telephone number is (571)272-6918. The examiner can normally be reached 7:00am-3:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A. Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SEONG JONG KIM/ Examiner, Art Unit 1621
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
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