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
Claim 16 was cancelled in a previous communication.
Claims 1-15 are pending and currently under examination.
Information Disclosure Statement
Initialed and dated copies of Applicants’ information disclosure statements (IDS) filed on 06/28/2024 is attached to the instant Office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119
(a)-(d). The certified copy has been received and placed in the file.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Objections
Claim 9 is objected to because of the following informalities: Claim 9 recites “SThe”, this appears to be a typographical error. Amending the claim to delete the letter “S” would be remedial. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 15 is 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 the step of administering or taking to a subject in need thereof a composition comprising a carnitine acylcarnitine carrier (CAC) inhibitor and a peroxisomal beta oxidation inhibitor, does not reasonably provide enablement for preventing or treating cancer.
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.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (A)).
These include:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based
on the content of the disclosure
All of the Wands factors have been considered with regard to the instant claims as discussed below:
(A)/(B) The breadth of the claims/The nature of the invention:
The claim is directed to a method of preventing or treating cancer, comprising the step of administering or taking to a subject in need thereof a composition comprising a carnitine acylcarnitine carrier (CAC) inhibitor and a peroxisomal beta oxidation inhibitor.
The scope of the phrase “cancer” is enormous. The claim places no limitation on the identity of the “cancer”. The term "cancer" is astronomical. According to the National Cancer Institute, "cancer'' embraces over 100 types of related proliferation disorders. Cancers are broadly classified into carcinoma, sarcoma, leukemia, lymphoma, multiple myeloma, melanoma, brain and spinal cord tumors, germ cell tumors, neuroendocrine tumors, and carcinoid tumors. Of these, only leukemia does not include solid tumors. Cancer types are subdivided by tissue of origin and are often subcategorized within that classification by histological markers or other clinical and histopathological features. See What is Cancer website, pages 4-7. In summary, the term “cancer” embraces hundreds of different diseases having different molecular mechanisms driving pathology and different responsiveness to therapies. Accordingly, the breadth of the claim is colossal in terms of the scope of cancer for claim 16.
(C)/(E) The state of the prior art/The level of predictability in the art:
In order to use the invention, as claimed, one having ordinary skill in the art would need to identify the full scope of cancer. With regard to cancer, in general response to cancer treatment strategies is highly unpredictable. Inter-individual variation in the patient population and genetic heterogeneity within the tumor itself make predicting response nearly impossible. In fact, the overwhelming majority of candidate drugs for treating cancer, for example, that succeed in preclinical testing will fail in clinical trials (Kamb, p 115, col 1, lines 1-4 and figures 1 and 2, page 116). As outlined in Box 1, there are many ongoing challenges to the development of combination targeted therapeutics for cancer, such as incomplete understanding of the mechanism of action of the molecularly targeted agent, exponentially growing number of agents and targets requiring clinical investigation, inability to assess target effects clinically, that is, lack of assays or imaging tools, and lack of assay standardization. Primary among these challenges is assessing the relationship of targeted agent development with the completeness of our understanding of the biology of their presumed targets of interest, both in their appropriate disease context and in the wide range of their potential drug interactions with various downstream effectors (Kummar, Main, third paragraph). Accordingly, it would be difficult for a person of ordinary skill in the art to predict which pathologies might respond to treatment with a composition comprising a carnitine acylcarnitine carrier (CAC) inhibitor and a peroxisomal beta oxidation inhibitor.
With respect to the state of the art of testing whether a compound will be able to treat cancer, candidate targets need to be screened in vitro or in tissue culture models for the ability to bind to cancer cell surfaces and then this must be validated in vivo to establish that binding occurs with sufficient affinity and specificity that the targeting agent will adhere strongly to tumor tissue and not to healthy tissues in the body. The publication by Mccann et al. is cited as an example of the procedures used in the art to accomplish this at the time the instant invention was filed. Mccann discloses that by convention, preclinical testing in animal models is used to validate candidate models but that this requires conventional histology and immunohistochemistry experiments that require large numbers of animals (abstract). Mccann discloses an experimental technique that may accelerate the procedures required to validate a targeting molecules. This procedure still requires an animal model of cancer wherein ovarian cancer takes 14 days to become established (page 195) and requires necropsy followed by in situ fluorescence imaging of each of the test subjects (pages 195-196). Therefore, even using McCann's experimental accelerated method, testing a single compound would take over two weeks to validate in pre-clinical models.
Finally, MPEP 2164.03 indicates that the physiological art in general is unpredictable. “A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971). However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because it is not obvious from the disclosure of one species, what other species will work.”
(D) The level of one of ordinary skill: One having ordinary skill in the art would be an individual possessing an advanced degree in medicine, biomedicine, or pharmaceutical sciences.
(F) The amount of direction provided by the inventor/(G) The existence of working examples:
The specification discloses a list of cancers such as breast cancer, colon cancer, glioblastoma, liver cancer, leukemia, melanoma, lung cancer, ovarian cancer, prostate cancer, pancreatic cancer, renal cell carcinoma, and gastric cancer. The examiner does not consider the cancers cited concisely in the specification provide enablement for practicing the full scope of the invention as embraced by the phrase “preventing or treating cancer”. Thus, varied examples are listed but no particular guidance is provided for one of ordinary skill in the art to immediately recognized that all cancers can be prevented or treated.
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
In view of the foregoing analysis, the examiner concludes that the quantity of experimentation required to practice the full scope of the invention, as claimed, would be undue.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-3, 5, 9-10 and 12 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.
Claims 2 and 9 recites “KN510”, “KN511”, and “KN512” in parentheses rendering the claim indefinite because it is unclear whether the limitations within the parentheses are part of the claimed invention. See MPEP § 2173.05(d). The examiner also points out that it is wholly unclear the meaning of “KN510”, “KN511”, and “KN512”.
Claims 3 and 10 recites “KN714” in parentheses rendering the claim indefinite because it is unclear whether the limitations within the parentheses are part of the claimed invention. See MPEP § 2173.05(d). The examiner also points out that it is wholly unclear the meaning of “KN714”.
Claims 5 and 12 recites “administered sequentially”. This language renders the claim indefinite because it is unclear if there is a single composition or multiple compositions based on the limitation of “administered sequentially”, however, the instant claim 1 recites a pharmaceutical composition comprising a carnitine acylcarnitine carrier (CAC) inhibitor and a peroxisomal beta oxidation inhibitor, therefore it is unclear how a single composition be administered sequentially.
Claim Rejections - 35 USC § 103
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.
Claims 1-15, are rejected under 35 U.S.C. 103 as being unpatentable over Bunt et al. (US20140235631A1, Published 08/21/2014).
Applicant’s Invention
The claims are drawn to a pharmaceutical composition for the prevention or treatment of cancer, comprising a carnitine acylcarnitine carrier (CAC) inhibitor and a peroxisomal beta oxidation inhibitor as active ingredients.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 1-3 and 8-10, Bunt teaches a composition comprising at least one efflux inhibitor enhances the penetration of one or more therapeutic agents across the blood-brain barrier and/or the blood-nerve barrier in mammals (paragraph [0006]). Bunt also teaches the efflux inhibitor is selected from one or more members of the group consisting of a Breast Cancer Resistance Protein (BCRP) inhibitor (paragraph [0009]), wherein the efflux inhibitor is a BCRP inhibitor selected from the group consisting of omeprazole, lansoprazole (i.e., carnitine acylcarnitine carrier (CAC) inhibitor) and thioridazine (i.e., a peroxisomal beta oxidation inhibitor)(paragraph [0010]).
Regarding claims 4 and 11, Bunt teaches a suitable dosage amount of the efflux inhibitor is in a range of about 0.1 mg/kg to about 250 mg/kg of body weight of the mammalian (paragraph [0074]).
Regarding claims 5 and 12, Bunt teaches the method comprising administering to the subject a therapeutic amount of the first aspect of the invention (i.e., efflux inhibitor is a BCRP inhibitor such as omeprazole, lansoprazole (i.e., carnitine acylcarnitine carrier (CAC) inhibitor) and thioridazine (i.e., a peroxisomal beta oxidation inhibitor) (i.e., simultaneously), and a therapeutic agent useful for treating the condition, wherein the composition enhances the concentration of the therapeutic agent in the target tissue or cell. The examiner further points out that the claim recites an intended use of the pharmaceutical composition being administered sequentially or simultaneously which does not limit the pharmaceutical composition.
Regarding claims 6 and 13, Bunt teaches the invention provides methods for preventing or treating a neurological condition or any disease present in sanctuary sites, e.g., brain, spinal cord, nerves, cerebrospinal fluid, testis, eyeballs, retina, inner ear, placenta, mammary gland, liver, biliary tract, kidney, intestines, lung, adrenal cortex, endometrium, hematopoietic cells, and/or stem cells such as breast cancer brain metastasis (BCBM), glioblastoma multiforme (paragraph [0027]). Bunt also teaches the methods and compositions disclosed herein are used in the treatment of neurological conditions such as brain cancer, lung cancer, chronic myelogenous leukemia, acute lymphoblastic leukemia (paragraph [0127]). The examiner further points out that the claim recites an intended use of the pharmaceutical composition being used for the prevention or treatment of cancer, wherein the cancer is one or more cancers which does not limit the pharmaceutical composition itself.
Regarding claims 7 and 14, Bunt teaches the therapeutic agent is an anti-cancer agent. Suitable anti-cancer agents include irinotecan, fluorouracil, paclitaxel, gemcitabine, cisplatin (paragraph [0054]). Bunt also teaches the therapeutic agent is yervoy (ipilimumab) (i.e., tumor immunosuppressive agent) (paragraph [0057]).
Regarding claim 15, Bunt teaches the present invention provides methods of preventing and/or treating and/or ameliorating a neurological condition (i.e., such as brain cancer, lung cancer, chronic myelogenous leukemia, acute lymphoblastic leukemia) in a mammalian (e.g., human) subject. In certain aspects, the invention is for use in combination therapy, whereby one or more inhibitors of BCRP (i.e., omeprazole, lansoprazole (i.e., carnitine acylcarnitine carrier (CAC) inhibitor) and thioridazine (i.e., a peroxisomal beta oxidation inhibitor)) and/or P-GP is administered to a mammalian (e.g., human) subject undergoing therapy with one or more inhibitors of tyrosine kinase (paragraph [0129]).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Bunt does not disclose a single embodiment or example where every limitation recited in the instant claims are taught.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
The claims are considered prima facie obvious to one of ordinary skill in the art because
Bunt teaches all of the claimed elements. It would have been prima facie obvious at the time
of filing to have a pharmaceutical composition for the prevention or treatment of cancer, comprising a carnitine acylcarnitine carrier (CAC) inhibitor and a peroxisomal beta oxidation inhibitor as active ingredients because Bunt teaches these elements as components of their invention.
With regards to claims 4 and 11, wherein the composition comprises the carnitine acylcarnitine carrier inhibitor and peroxisome beta-oxidation inhibitor in a concentration ratio of 100:1 to 1:100, it would have been obvious to one of ordinary skill to optimize the concentration ratio. One would have understood in view of Bunt that a suitable dosage amount of the efflux inhibitor is in a range of about 0.1 mg/kg to about 250 mg/kg of body weight of the mammalian (paragraph [0074]). Therefore, it would have been obvious to optimize to the concentration ratio of the carnitine acylcarnitine carrier inhibitor and peroxisome beta-oxidation inhibitor by routine experimentation to adjust concentration ratio using Bunt’s teachings as a starting point for the desired results of the pharmaceutical composition concentration ratio. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFUA BAMFOAA BOATENG whose telephone number is (703)756-1358. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571) 272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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AFUA BAMFOAA BOATENGExaminer, Art Unit 1617
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
