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 .
DETAILED ACTION
The preliminary amendment filed 06/20/2023, amended claims 2, 4, 6, 8, and 10.
Claims 1-10 are pending and examined on the merits herein.
Priority
This application claims the following priority:
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Request for Information
Applicant and the assignee of this application are required under 37 CFR 1.105 to provide the following information that the examiner has determined is reasonably necessary to the examination of this application.
In response to this requirement, please provide a copy of each of the following items of art referred to in the specification. On pg. 20 of the specification, The Chembridge Diverset library with 30,000 small molecules is referenced. 4-benzyoyl-2-methylphenyl (2-nitropheonxy) acetate is recited in [0075] of the specification as one of these 30,000 small molecules. However, STN Registry File states that this compound entered Registry on 05/14/2019, while the effective filing date of the instant application is 10/16/2017. As such, it appears that Applicant has possession of pertinent prior art from Chembridge or another source, i.e., compound
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For this reason, the request for information is being made.
Claim Objections
Claim 5 is objected to because of the following informalities:
The term “methyl” is misspelled in claim 5; “methy” should be replaced with - -methyl- -
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 2, 4, 6, 8, and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The phrase “increasing effectiveness” in claims 2, 4, 6, 8 and 10, is a relative term which renders the claim indefinite. This phrase is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
It is not clear what baseline measurement or measuring tool is being relied upon to measure an “increased effectiveness.” Moreover, the metes and bounds of the term “effectiveness” is unclear. For example, it is unclear if “effectiveness” is a measure of tumor size, a measure of side effects, a measure of length of chemotherapeutic regimen, etc.
As such, this phrase is indefinite.
Claim Interpretation
The instantly claimed compounds are interpreted as having the following structures:
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4-benzoyl-2-methylphenyl (2-nitrophenoxy) acetate:
N-benzyl-2-([bis(furan-2-yl)-1,2,4-triazin-3-yl] sulfanyl acetamide:
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6-(benzylcarbamoyl)-1-methylcyclohex-3-ene-1-carboxylic acid:
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8-(phenylamino)naphthalene-1-sulfonic acid:
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benzyl 6-(furan-2-yl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-2-carboxylate:
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.
Claim Rejections - 35 USC § 112(a)-Scope of Enablement
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 2, 4, 6, 8, and 10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of inhibiting TREX2 by administering a pharmaceutical composition comprising 4-benzoyl-2-methylphenyl (2-nitrophenoxy) acetate, N-benzyl-2-([bis(furan-2-yl)-1,2,4-triazin-3-yl] sulfanyl acetamide, 6-(benzylcarbamoyl)-1-methylcyclohex-3-ene-1-carboxylic acid, 8-(phenylamino)naphthalene-1-sulfonic acid, or benzyl 6-(furan-2-yl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-2-carboxylate, does not reasonably provide enablement for a method for increasing the effectiveness of a chemotherapeutic agent in a mammalian cancer cell comprising administering to mammalian cancer cell exposed to a chemotherapeutic, a pharmaceutical composition comprising 4-benzoyl-2-methylphenyl (2-nitrophenoxy) acetate or a derivative thereof, N-benzyl-2-([bis(furan-2-yl)-1,2,4-triazin-3-yl] sulfanyl acetamide or a derivative thereof, 6-(benzylcarbamoyl)-1-methylcyclohex-3-ene-1-carboxylic acid or a derivative thereof, 8-(phenylamino)naphthalene-1-sulfonic acid or a derivative thereof, or benzyl 6-(furan-2-yl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-2-carboxylate or a derivative 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 use the invention commensurate in scope with these claims.
The criteria for enablement set out in the In re Wands, MPEP 2164.01(a), considers the following factors:
Breadth of the Claims
The instant claims are directed toward a method of increasing the effectiveness of a chemotherapeutic agent in a mammalian cancer cell comprising administering to any mammalian cancer cell, in vivo or ex vivo, exposed to any chemotherapeutic agent, a pharmaceutical composition comprising 4-benzoyl-2-methylphenyl (2-nitrophenoxy) acetate or a derivative thereof, N-benzyl-2-([bis(furan-2-yl)-1,2,4-triazin-3-yl] sulfanyl acetamide or a derivative thereof, 6-(benzylcarbamoyl)-1-methylcyclohex-3-ene-1-carboxylic acid or a derivative thereof, 8-(phenylamino)naphthalene-1-sulfonic acid or a derivative thereof, or benzyl 6-(furan-2-yl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-2-carboxylate or a derivative thereof.
Thus, the claims are directed toward any type of cancer, any chemotherapeutic, and any derivative of the recited compounds. As such, the breadth of the claims is great.
Level of Skill in Art
The level of skill in the art is a clinician or an scientist with a PhD.
State of the Prior Art
STN File Registry, RN 483293-23-8 (PTO-892) teaches:
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, the compound of claim 3.
STN File Registry, RN 694475-06-4 (PTO-892) teaches:
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, the compound of claim 5.
However, neither registry file teaches these compounds in pharmaceutical compositions, let alone in methods for increasing the effectiveness of a chemotherapeutic agent.
US PG-PUB 2010/022759 to Yamauchi (published 2010, PTO-892) teaches a composition comprising aninlonaphthalenesulfonic acid,
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, the compound of claim 7, and water ([0071]; [0016]-[0017], [0076]-[0077]).
However, Yamauchi teaches these compounds for use as dyes for the detection of lesions (pg. 9, claims 1-12), and not in methods for increasing effectiveness of a chemotherapeutic agent.
WO 2012/027392 to Hansen teaches pharmaceutical compositions comprising:
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(pg. 75, claim 135) and specifically teaches C-15 as a species of
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:
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(pg. 43), and teaches a method of preventing or treating cancer by administering the composition and a chemotherapeutic (pg. 44; pg. 78, claim 156).
However, Hanson does not teach its methods for increasing effectiveness of a chemotherapeutic agent.
In summary, the prior art is silent regarding the compound recited in claim 2, the prior art does not teach pharmaceutical compositions comprising the compounds of claims 4 and 6, and the prior art does not teach the instantly claimed methods of any of claims 2, 4, 6, 8, or 10.
Predictability in the Art
The American Cancer Society (Chemotherapy, PTO-892) teaches that there are many different types of chemo and that they do not all work exactly the same way; different types of chemo might be used for different types of cancer (pg. 1 2nd full paragraph).
Cancer Research UK (How chemotherapy works, PTO-892) teaches that chemotherapy has different effects on different types of cancer (pg. 1), and that the chance of the chemotherapy curing your cancer depends on the type of cancer you have. With some cancers, chemotherapy cannot cure the cancer on its own, but can help in combination with other types of treatment (“How well chemotherapy works”).
Warrick (The Conversation, “Every cancer is unique-why different cancers require different treatments, and how evolution drives drug resistance, PTO-892) teaches that cancers from different organs look distinct from one another and contain different proteins. Tumors arising in a given organ also tend to have mutations in the same set of genes, even among different patients (pg. 3). Because of differences in proteins and mutations, tumors from different organs respond differently to treatment. For example, the majority of patients with testicular cancer can be cured with traditional chemotherapy combined with surgery. However, thyroid cancer and melanoma respond minimally to chemotherapy and require different approaches (pg. 4).
Thus, the effectiveness of chemotherapy depends on the type of cancer and the type of chemotherapeutic. Moreover, not all cancers respond to chemotherapy.
As such, the art of treating different cancer is unpredictable as is treating cancers with chemotherapeutics.
Working Examples
The instant specification provides zero examples of a method of increasing the effectiveness of a chemotherapeutic agent by administering the instantly claimed compositions to a mammalian cancer cell exposed to a chemotherapeutic.
It is noted that Example 16 on pg. 29 of the specification provides a prophetic example, but even this example does not mention the administration of a chemotherapeutic agent.
Example 8, beginning on pg. 20 of the specification, exemplifies compounds 1 (compound of claim 1), 6 (compound of claim 7), 10 (compound of claim 3), and 11 (compound of claim 5). However example 8 is directed towards these compounds demonstrating their effectiveness as inhibitors of TREX2.
Direction and Guidance
In view of the broad scope of the claims, the unpredictability of the art, and the lack of working examples, the instant specification does not provide sufficient direction or guidance to use the invention as claimed in claims 2, 4, 6, 8 and 10.
Quantity of Experimentation
In view of the great variety of cancers, the great number of distinct chemotherapeutics, and the great number of derivatives of the instantly recited compounds, the amount of experimentation required to determine which compounds, including their derivatives, are effective to increase the effectiveness of which chemotherapeutic agents for which cancers, would be astronomical, amounting to invention and not development. The amount of experimentation is undue.
Thus, while being enabling for a method of inhibiting TREX2 by administering a pharmaceutical composition comprising 4-benzoyl-2-methylphenyl (2-nitrophenoxy) acetate, N-benzyl-2-([bis(furan-2-yl)-1,2,4-triazin-3-yl] sulfanyl acetamide, 6-(benzylcarbamoyl)-1-methylcyclohex-3-ene-1-carboxylic acid, 8-(phenylamino)naphthalene-1-sulfonic acid, or benzyl 6-(furan-2-yl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-2-carboxylate, does not reasonably provide enablement for a method for increasing the effectiveness of a chemotherapeutic agent in a mammalian cancer cell comprising administering to mammalian cancer cell exposed to a chemotherapeutic, a pharmaceutical composition comprising 4-benzoyl-2-methylphenyl (2-nitrophenoxy) acetate or a derivative thereof, N-benzyl-2-([bis(furan-2-yl)-1,2,4-triazin-3-yl] sulfanyl acetamide or a derivative thereof, 6-(benzylcarbamoyl)-1-methylcyclohex-3-ene-1-carboxylic acid or a derivative thereof, 8-(phenylamino)naphthalene-1-sulfonic acid or a derivative thereof, or benzyl 6-(furan-2-yl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-2-carboxylate or a derivative thereof.
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 7 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by US 2010/022759 to Yamauchi (published 2010, PTO-892).
Yamauchi teaches aninlonaphthalenesulfonic acid,
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in water, ([0071]; additionally, [0016]-[0017], [0076]-[0077]).
Claim 9 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by WO 2012/027392 to Hansen (published 2012, PTO-892).
Hansen teaches pharmaceutical compositions comprising:
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(pg. 75, claim 135) and specifically teaches C-15 as a species of
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(pg. 43).
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 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.
Claims 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2012/027392 to Hansen (published 2012, PTO-892).
Hansen is applied to claim 9 as discussed above.
While Hansen teaches a pharmaceutical composition comprising benzyl 6-(furan-2-yl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-2-carboxylate, it differs from that of instant claim 10 in that it does not teach administering the compound to a mammalian cancer cell exposed to the chemotherapeutic agent.
Hansen teaches a method of preventing or treating cancer by administering a composition comprising
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(pg. 78, claim 156).
Hansen teaches its patients as mammals.
Hansen teaches that its compounds can be administered with other anti-cancer agents, such cisplatin and other chemotherapeutics (pg. 44).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to add a chemotherapeutic agent to the composition of Hansen comprising compound C-15, to arrive at instant claim 10. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, because Hansen teaches that chemotherapeutics can be added to its compositions for the prevention or treatment of cancer.
An artisan having ordinary skill in the art would have been motivated to make such an addition to predictably arrive at a more therapeutically potent method of treating cancer.
While Hansen does not teach “A method of increasing effectiveness of a chemotherapeutic agent,” the method of Hansen teaches administering to a mammalian cancer cell, a composition comprising both the instantly claimed composition and a chemotherapeutic.” As such, since instant claim 10 and Hansen teach administering the same composition to the same patient population, it would reasonably be expected that the method of Hansen increases the effectiveness of the chemotherapeutic. See MPEP 2112.02.
Allowable Claims & Claims Free of the Prior Art
Claims 1, 3, and 5 are allowed.
Claims 2, 4, 6 and 8 are free of the prior art.
The closest prior art to claims 1-2 is Campbell (The Use of BenzoPhenone as a Photoaffinity Label. Labeling in p-Benzoylphenylacetyl chymotrypsin at Unit Efficiency, Photochem and Photobio, published 1979)), which teaches:
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(pg. 884, Col. 2, “Results”). However, Campbell does not teach a methyl on the middle phenyl ring and does not teach NO2 at the 2 position of the phenoxy ring, and further does not teach a pharmaceutical composition comprising this compound, let alone a method of administering the composition to a mammalian cancer cell exposed to a chemotherapeutic agent, which are the distinct features of the instantly claimed composition.
The closest prior art to claims 3-4 is STN File Registry, RN 483293-23-8 (Entered STN, 01/30/2003, PTO-892).
STN teaches:
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However, STN Registry File does not teach a pharmaceutical composition comprising this compound, let alone a method of administering the composition to a mammalian cancer cell exposed to a chemotherapeutic agent, which are the distinct features of the instantly claimed composition.
The closest prior art to claims 5-6 is STN File Registry, RN 694475-06-4 (Entered STN on 06/17/2004, PTO-892), which teaches:
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However, STN Registry File does not teach a pharmaceutical composition comprising this compound, let alone a method of administering the composition to a mammalian cancer cell exposed to a chemotherapeutic agent, which are the distinct features of the instantly claimed composition.
The closest prior art to claim 8 is US 2010/022759 to Yamauchi (published 2010, PTO-892).
While Yamauchi teaches aninlonaphthalenesulfonic acid,
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in water, ([0071]; additionally, [0016]-[0017], [0076]-[0077]), it does not teach a method of administering the composition to a mammalian cancer cell exposed to a chemotherapeutic agent, which are the distinct features of the instantly claimed method.
Conclusion
Claims 1, 3, and 5 are allowed. Claims 2, 4 and 6-10 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAUREN WELLS/Examiner, Art Unit 1622