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 office acknowledges Applicants filing of the claim amendments dated 3/17/2023. Claims 1-16 have been amended and claims 18-20 have been added new. Claims 1-20 are pending and are examined based on the merits herein.
Application Priority
This application filed 03/17/2023 is a National Stage entry of PCT/IB2021/ 058522, International Filing Date: 09/18/2021, claims foreign priority to 102020000022066, filed 09/18/2020.
Information Disclosure Statement
The information disclosure statement(s) (IDS) filed on 3/30/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being considered by the Examiner.
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.
Claims 2-8, 20 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 the effects of compound L1 in CaCo2 (human epithelial adenocarcinoma cell) and T98G (glioblastoma cell line) in vitro cell lines, does not reasonably provide enablement for the treatment of all tumors as claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, "The Federal Circuit has repeatedly held that "the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation." In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)" (emphasis added). The "make and use the full scope of the invention without undue experimentation" language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: "A lack of enablement for the full scope of a claim, however, is a legitimate rejection." The principle was explicitly affirmed most recently in Liebel-Flarsheim Co. v. Medrad, Inc., 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int'l, Inc. v. BMWofN. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc.,503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008).
In evaluating the enablement question, several factors are to be considered. Note In re Wands, 8 USPQ2d 1400 and Ex parte Forman, 230 USPQ 546. The factors include: 1) The nature of the invention, 2) the breadth of the claims, 3) the predictability or lack thereof in the art, 4) the state of the prior art, 5) the presence or absence of working examples, 6) the amount of direction or guidance present, 7) the relative skill of those in the art and 8) the quantity of experimentation needed. The determination that “undue experimentation” would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations.
(1)/(2) The nature of the invention & breadth of claims:
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The dependent claims 3-4 are limited to bowel or colorectal (claim 3), and glia or glioblastoma (claim 4). The other dependent claims are limited to individuals being humans or animals, therapeutically effective amount of the compound L1, formulated for pediatric administration, rapid, prolonged delayed release formulation administered, and additional anti-tumor agents in the method.
The claims 2, 5-8, 20 encompass a large scope of tumors to be treated, individuals to be treated (humans and genus/subgenus of different variety and types of animals) and additional anti-tumor agents. Claims 3-4 are limited to specific tumor/cancer types but in regards to individuals to be treated include adult humans, adolescent and pediatric children; and genus/subgenus of different variety and types of animals. The treatment of tumors in humans may not be applicable to animals.
The instant claims are to a method for treating several types of tumors. According to National Cancer Institute, “An abnormal mass of tissue that forms when cells grow and divide more than they should or do not die when they should. Tumors may be benign (not cancer) or malignant (cancer). Benign tumors may grow large but do not spread into, or invade, nearby tissues or other parts of the body” (https://www. cancer.gov/publications/dictionaries/cancer-terms/def/tumor, 2025). It is noted that all cancers are tumors but not all tumors are cancerous.
A 'cancer' or 'tumor growth' is anything that causes abnormal tissue growth. That can be growth by cellular proliferation more rapidly than normal, or continued growth after the stimulus that initiated the new growth has ceased, or lack (partial or complete) of structural organization and/or coordination with surrounding tissue. It can be benign or malignant. Thus, such term covers not only all cancers, but also covers precancerous conditions such as lumps, lesions, polyps, etc. No compound has ever been found to treat tumors or cancers of all types generally. Since this assertion is contrary to what is known in medicine, proof must be provided that this revolutionary assertion has merits. The existence of such a “silver bullet” is contrary to our present understanding of oncology. The state of the art is not indicative any pharmaceutical agents that are useful in the treatment of cancer generally. Cecil Textbook of Medicine states that “each specific type has unique biologic and clinical features that must be appreciated for proper diagnosis, treatment and study” (see the enclosed article, page 1004). Different types of cancers affect different organs and have different methods of growth and harm to the body. Also see In re Buting, 163 USPQ 689 (CCPA 1969), wherein 'evidence involving a single compound and two types of cancer, was held insufficient to establish the utility of the claims directed to disparate types of cancers'. Thus, it is beyond the skill of oncologists today to get an agent to be effective against cancers generally.
Further, there is no established single anti-proliferative therapeutic agent for all these types of diseases, which are characterized by the proliferation of tumor cells. The ideal chemotherapeutic drug would target and destroy only cancer cells without adverse effects or toxicities on normal cells. Unfortunately, no such drug exists; there is a narrow therapeutic index between cell kill of cancer cells and that of normal cells. Successful treatment of cancer requires elimination of all cancer cells, whether at the primary site, extended to local-regional areas, or metastatic to other regions of the body. The major modalities of therapy are surgery and radiotherapy (for local and local-regional disease) and chemotherapy (for systemic sites). For example, regarding the treatment of leukemia, The Merck Manual (online edition) states, that “Treatment programs and clinical situations are complex”. Dosage regimen is dependent on several risk factors and the contribution of each active ingredient of a multidrug combination therapy is complex and unclear.
Taken as a whole, the skill level in oncology must be considered as low. "It should be noted that oncology has the lowest success rates of any therapeutic area." Cancer Drug Design and Discovery Neidle, Stephen, ed. (Elsevier/Academic Press, 2008) page 431. There is even some understanding why this is so. Preclinical testing relies on immortal in vitro cell lines, but "Cell lines derived under artificial conditions and propagated for decades are not likely to be realistic, or to provide meaningful targets." (page 428). The next step is animal models, but "Preclinical efficacy models in cancer drug discovery ... are usually rodent models bearing a transplantable tumor. Yet the vast majority of these investigational drugs fail to meet their pre-specified clinical benefit or efficacy endpoints. The predictive quality of standard animal models has been assessed in a retrospective analysis, with the conclusion that tumor specificity does not translate from laboratory to clinic. Human tumor xenografts that present tumors of a particular histology and tissue of origin do not predict for clinical activity in that tumor" (page 427). In other words, successful animal tests with human tumor xenografts with cancer X do not predict success in humans with cancer X.
Another part of the problem is that it is recognized that anti-cancer drugs are generally anomalous (as compared to other types of drugs), which greatly limits the ability to use general pharmacological knowledge: "Clearly, the ability to predict acceptable pharmaceutical properties based on chemical structure would be highly desirable. In an attempt to meet this challenge "Lipinski's Rules" were formulated, based on a retrospective analysis of success rates of new orally administered agents entering early clinical trials .... Interestingly, most commonly used cancer drugs fail to satisfy these criteria .... Many marketed anticancer drugs break most of the rules of good pharmacokinetic (PK) behavior." (page 429).
Yet another area of low skill level is the obstacle of poor understanding of resistance mechanisms, which so often prevent drug candidates from being successful: "The most common cause of treatment failure of metastatic cancer is drug resistance. Resistance mechanisms remain an undetermined obstacle to the successful discovery and development of novel targeted therapies. The genomic instability that is a hallmark of cancer contributes to the ability of tumors to develop resistance during therapy (acquired resistance), and the intrapatient heterogeneity of most advanced solid tumors invariably leads to the selection of resistant clones (intrinsic resistance)." (page 430).
The scope of instant claims includes a method of treating a tumor and it is not established how one of ordinary skill in the art would be able to extrapolate the data provided in the specification to the entire scope of the instant claims. See, for example, the state of the art references, Gura et al. (Science 1997) and Johnson et al., (British J. of Cancer 2001) - Gura et al., teaches that researchers face the problem of sifting through potential anticancer agents to find the ones promising enough to make human clinical trials worthwhile and further teach that since formal screening began in 1955, many thousands of drugs have shown activity in either cell or animal models but that only 39 have actually been shown to be useful for chemotherapy (see the first two paragraphs).
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. Also, with regard to unpredictability, Johnson et al., teaches that the in vivo activity of 39 different agents in a particular histology in a tumor model did not correlate to activity in the same human cancer. These state of the art references plainly demonstrate that the art of developing and testing anticancer drugs particularly for use in humans is extremely unpredictable, particularly in the case of a single compound or genus of compounds being used to treat any and all cancers.
Applicant in the specification in regards to treating tumor, state in page 2,
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There are hundreds of tumor and cancer types as per National Cancer Institute (NCI, https://training.seer.cancer.gov/disease/categories/tumors.html, 2025).
Applicants have not provided any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use of the instant compound L1 in the treatment of different types of tumors that occur in different organs, tissues etc. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved”. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
(3)/(4) predictability in the art & the state of the prior art:
Despite the advance training of those in the art, the art is highly unpredictable. It is still not possible to predict the pharmacological activity or treatment efficacy of a compound based on the structure alone. It is also not possible to predict the efficacy of a given class of compounds for the treatment of a particular disease absent a mechanistic link between the pharmacological activity of the class of agents and the etiology or pathophysiology of the disease. Typically, in order to verify that a compound will be effective in treating a disease, the compounds must be tested either directly in a patient or in a model that has been established as being predictive of treatment efficacy. In order to predict whether a class of compounds would be effective in treating a disease, the etiology or pathophysiology of the disease must be uncovered, and there should be a nexus between the pharmacological activity of the class of agents and the etiology or pathophysiology of the disease. Even if the mechanism is defined for a particular class of drugs it is not predictable from such studies that each drug that falls into the class will be useful in treating the condition without any severe adverse or side effects.
Treatment by Cancer Type: While the state of the art is relatively high with regard to the treatment of specific cancers with specific agents, it has long been underdeveloped with regard to the treatment of cancers broadly. In particular, there is no known anticancer agent, which is effective against all cancers. This is why the National Cancer Institute (NCI) has the extensive in vitro drug screening program it does. As discussed by the court in In re Brana, 51 F.3d 1560 (Fed. Cir. 1995), in vitro assays are used by NCI (such as the P388 and L1210 lymphocytic leukemia tests at issue therein) to measure the potential antitumor properties of a candidate compound. Brana at 1562-63. If success is shown in this initial screening step, this demonstrates that at least one cancer type (e.g., lymphocytic leukemia) is sensitive thereto, and provides the incentive to select it for further studies to determine its usefulness as a chemotherapeutic agent against other cancer types (lung, breast, colon, etc.) Id. at 1567-68. These in vitro tests are considered reasonably correlative of success in vivo. Thus, a considerable amount of in vitro empirical testing is required, with no a priori expectation of success being present, before a candidate anticancer agent can be considered useful against any particular cancer type.
The disclosure does not provide any guidance towards the dosage regimen required to facilitate the treatment of all the claimed tumor diseases, nor indicate competent technical references in the appropriate methods. Pediatric Cancer Research teach in page 1, ‘From leukemias and lymphomas to carcinomas and sarcomas, there are many, many different types of cancers, and no two are identical. Just as there are major differences between brain cancer and blood cancer, so too is there a world of difference between cancers in children and cancers in adults’. Differences between pediatric and adult cancers begin at the fundamental level. Indeed, they are present in the very biologies of the disparate age groups. Additionally, while differences in biology mean that breakthroughs in adult cancer treatment don’t always translate into comparable advances for pediatric patients, pediatric cancer researchers nevertheless benefit from prior research conducted using adult subjects (See Pediatric Cancer Research, 2025, https://pcrf-kids.org/2024/03/27/ understanding-the-differences-between-pediatric-adult-cancers/).
The following teachings in the instant specification adds on to the unpredictable nature of the pharmacological activity, (See page 2, 6, 13, 11-12, 2 respectively).
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It is taught in MDEdge that ‘Despite the success of Kojic acid at 1% concentration, particularly in Japan, some studies have indicated that longer term use of the agent may engender contact dermatitis, erythema, an association between hepatic tumor in heterozygous p53-deficient mice and the topical application of kojic acid has been identified (See p 3, para 4 of (MDEdge, https://ma1.mdedge.com/content/kojic-acid, 2019).
In regards to glia and glioblastoma as claimed (claim 4), glia tumor is a general term for tumors that develop from glial cells in the brain and spinal cord, while glioblastoma is a specific, highly aggressive type of glioma (also known as glioblastoma multiforme or GBM). According to Cleveland Clinic, “There are several types, including astrocytomas, ependymomas and oligodendrogliomas. Gliomas can affect children or adults. Some grow very quickly. Most people with gliomas need a combination of treatments such as surgery, radiation therapy and chemotherapy” (See p1, para 1, https://my.clevelandclinic.org/health/diseases/21969-glioma, 2025).
According to PetcureOncology.com, chemotherapy is not as common in animals as radiation or surgery, chemotherapy can be used in conjunction with other treatments, and especially when very aggressive gliomas are suspected (see page 3, lines 2-3, https://petcureoncology.com/gliomas-in-dogs/#:~:text=Treatment%20Options%20for %20Dogs%20with%20Gliomas&text=Surgery%3A%20When%20feasible%2C%20surgical%20removal,reduce%20and%20control%20tumor%20growth, 2025).
(5)/(6) Amount of guidance/working examples:
It has been established that, “The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839 166 USPQ 18, 24 (CCPA 1970).
The specification and prior art provides guidance in the synthesis of compound L1, the formulations that can be made with different excipients and carriers, list of additional anti-tumor agents, and in vitro tests of compound L1 with two cell lines, CaCo2 (human epithelial adenocarcinoma cell) and T98G (glioblastoma cell line). Though the specification provide in vitro data with L1 in T98G glioblastoma cell line, the specification do not provide evidence to how it can be extrapolated in treating any glia tumor or glioblastoma as chemotherapy is not as common as surgery or radiation in animals according to petcureoncology.com.
The specification do not provide guidance to how this data can be extrapolated to in vivo in general, treating different types of tumors in humans and in animals. Further there is no data or evidence to how this treatment further treats tumor relapses and metastasis in animals and humans. According to Kilmister, cancer metastasis and treatment resistance are the main causes of treatment failure and cancer-related deaths (See Abstract). An effective treatment of cancer may require a multi-target strategy with multi-step inhibition of signaling pathways that regulate CSCs and the TME, in lieu of the long-standing pursuit of a ‘silver-bullet’ single-target approach (See Kilmister et al. Abstract, Biomedicines 2022, 10, 2988).
(7) The relative skill of those in the art:
The relative skill in the art is fairly high, with the typical practitioner having a medical degree and/or an advanced degree in the biochemical, chemistry or pharmaceutical-related arts.
(8) The quantity of experimentation needed:
In order to enable the instantly claimed method commensurate with the entire scope, a large quantity of experimentation would be necessary. With Applicants’ guidance and data provided in the specification and what is known in the prior art the person of ordinary skill in the art would have to conduct experiments testing the compound L1 for treating hundreds of different types of tumors in human adults, human children and various species of animals. In order to practice the above claimed invention, one of ordinary skill in the art would have to first envision formulation, dosage, duration, route and, in the case of human treatment, an appropriate animal model system to test the compounds to determine whether or not they are useful in treating the disorders claimed. If unsuccessful, one of ordinary skill in the art would have to envision a modification in the formulation, dosage, duration, route of administration etc. and appropriate animal model system, or envision an entirely new combination of the above and test the system again. Considering the unpredictability of whether L1 compound would be useful in treating every single tumor this would be an arduous and daunting task. Considering the above-mentioned factors and the fact that there are significant inter-individual variability in using a pharmacological modalities in human subjects, the nature of art is unpredictable, and the breadth of the claims; one of ordinary skill in the art would be burdened with undue "experimentation study" to determine compound L1’s use in treating the tumors as claimed in any individual (humans and animals). Therefore, it would require undue, unpredictable experimentation to practice the claimed invention of a method of treating different types of tumors in an individual, e.g. human adults and/or in children comprising administering compound L1 or its composition. Genetech, 108 F.3d at 1366 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 5-6 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
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Claim 2 recites a limitation of ‘treating tumor in an individual’. The instant specification do not provide a specific definition for the ‘individual’. The meaning according to Merriam-Webster dictionary for an ‘individual’ is as follows: a particular being or thing as distinguished from a class, species, or collection: such as (a) (i) a single human being as contrasted with a social group or institution a teacher who works with individuals (ii) a single organism as distinguished from a group; (b) a particular person.
Accordingly in claim 2, if ‘individual’ is interpreted to be a ‘person’ or an ‘animal’ to be treated, claim 5 is not further limiting.
For the sake of compact prosecution, the claims are examined based on the interpretation that the individual is a human and/or an animal. Appropriate correction is required.
It is noted that Claim 6 depends on claim 5 which depends on claim 2. Claim 2 is to treating a tumor. Claim 6 recites a limitation of ‘treats tumor’ and it is not further limiting.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 6-8, 14, 16, 17-20 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.
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It is noted that there is a limitation to ‘pharmaceutically effective amount’ in claim 2 and ‘therapeutically effective amount’ in claims 6-8. The instant specification in page 8, lines 3-5 teach “The pharmaceutically effective amount mentioned above refers to an amount sufficient to prevent, improve and cure the tumor and according to our preliminary data it could correspond to about 0.5 and 5 mg/day/kg of body weight”. There is no definition provided for ‘therapeutically effective amount’ in the instant specification. In general ‘therapeutically effective amount’ is defined as the amount of a compound that, when administered to a patient for treating a disease, is sufficient to effect such treatment for the disease’.
It is not clear how pharmaceutically effective amount is different from therapeutically effective amount as claimed. For the examination purposes claims 6-8 has been examined based on ‘pharmaceutically effective amount’. Appropriate correction/clarification is required.
Further to the limitation of ‘therapeutically effective amount’ in claims 6-8, claim 2 do not have such limitation. Hence there is insufficient antecedent basis for this limitation in the claim.
In regards to claim 14,
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It is not clear how the compound of claim 1 can have additional tumor compound. Also it is not clear whether the compound is being referred to compound of claim 1 or the additional tumor compound. Appropriate correction is required.
For examination purposes the claim has been interpreted as the formulation comprises the compound of claim 1 and additional anti-tumor compound selected from.
As to claims 15-16,
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Claim 16 depends on claim 15. Claim 16 recites a limitation of ‘food’ in line 2. Claim 15 is a food comprising the compound of claim 1. It is not clear how the food in claim 15 is formulated as a food again. If it is specific food type? It is suggested that the claim be amended accordingly.
In regards to claim 17,
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Claim 17 depends on claim 10. Claim 10 is the formulation of the compound. Claim 17 has to be a formulation as the compound cannot have a carrier, excipient etc. For examination purposes the claim has been interpreted as formulation comprising the carrier, excipient etc. Appropriate correction is required.
As to claim 19,
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Claim 19 depends on claim 1. There is no antecedent basis for pharmaceutically effective amount as claim 1 is to a compound. For examination purposes it has been interpreted that it depends on method claim 2. Appropriate correction is required.
In regards to claim 20,
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Claim 20, in lines 1-2, recites a limitation of ‘comprising administering an additional anti-tumor compound’. However in line 4, ‘wherein the optionally additional tumor compound’ is recited. It is not clear whether the additional anti-tumor compound is essential or optional. Appropriate correction is required.
Note: For examination purposes the claim has been examined that additional tumor agent is administered.
Claim Objections
Claims 11-13, 16 are objected to because of the following informalities: In claims 11-13, after ‘The compound of claim 1,” in line 1, and in claim 16, ‘The food according to claim 15’, “is” is missing. It is suggested that claims be amended as ‘The compound of claim 1, is formulated’ and in claim 16, ‘‘The food according to claim 15, is formulated’
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, 9-10 are rejected under 35 U.S.C. 102(A)(1) as being anticipated by Nurchi et al. (IDS: J of Inorganic Biochemistry, 2018).
Nurchi et al. is explicit in teaching the compound L1 of instant claim 1 (compound S2 below) as a kojic acid derivative (See Fig. 1 and Fig 2).. Further taught is that the solution comprising S2, S3 and water for NMR measurements (See p 106, col. 1, 2.4 NMR Measurements).
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Thus Nurchi anticipates claims 1, 9-10 by teaching the compound L1 of claim 1 and its pharmaceutical composition in water, a carrier. It is noted that claim 1 is to a ‘compound’ and not to a method of use. Hence in regards to limitation ‘for use in a therapy’, it is an intended use. Applicants are reminded that claim language which merely recites a purpose or intended use of a claimed invention that is otherwise fully and intrinsically set forth by the remainder of the claim, such language is of no consequence to the construction of the invention claimed. MPEP 2111.02(II). Statements of intended use do not serve to distinguish structure over the prior art. See In re Pearson, 494 F .2d 1399, 1403, 181 USPQ 641, 644 (CCPA 1974); In re Yanush, 477, F .2d 958, 959, 177 USPQ 705, 706 (CCPA 1973); In re Casey, 370 F .2d 576, 580, 152 USPQ 235, 238 (CCPA 1967).
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.
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.
Claim(s) 1, 2, 4-12, 15-19 are rejected under 35 U.S.C. 103 as being unpatentable over Nurchi et al. (IDS: J of Inorganic Biochemistry, 2018) in view of Cho et al. (KR 20110054448 A, See English translation).
Nurchi et al. is explicit in teaching the compound L1 of instant claim 1 (compound S2 below) as a kojic acid derivative (See Fig. 1 and Fig 2). Further taught is that the solution comprising S2, S3 and water for NMR measurements (See p 106, col. 1, 2.4 NMR Measurements).
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Nurchi is not explicit in teaching the use of L1, a kojic acid derivative for use in treating tumor, e.g. glioblastoma.
Cho disclose kojic acid derivatives are useful in treating glioma-derived tumor, in a mammal, e.g. humans (See abstract, claims 1, 7 and 8). Cho provides a method and data for inhibiting proliferation of glioma cells with a compound of formula I, kojic acid derivative(s), see Examples 1-2. Cho further teach that the present invention may include a pharmaceutically effective amount of kojic acid derivative compound alone or may include one or more pharmaceutically acceptable carriers, excipients or diluents, examples of such carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, the compositions of the present invention may be formulated using methods known in the art so as to provide rapid, sustained or delayed release of the active ingredient after administration to the mammal; formulations may be in the form of powders, granules, tablets, emulsions, syrups; the pharmaceutically effective amount of the kojic acid derivative can range from 0.5-100 mg/day/kg (See p 10, para 1-5). Cho teach that glioma that can be treated with kojic acid derivatives according to the present invention may include astrocytoma, ventricular ductoma, oligodendrocyte glioma and mixed glioma of adults and children (See p 6, para 1). Cho teach that the anticancer composition of the present invention can be added to food for the purpose of preventing or improving cancer, and thus the composition of the present invention can be used as a functional health food composition having an anticancer effect; food includes special nutritional products (e.g., formulated milk, young, infant food, etc.); the food includes, food additive, functional foods and drinks (See p 10, para 8-10).
From Cho a skilled artisan before the effective filing date of the invention would have found it obvious that kojic acid derivative can be used in the inhibition of the proliferation of the glioma cells and thus treat glioma cancer. A person skilled in the art from such teachings would have found it obvious to try another kojic acid derivative, for e.g. kojic acid derivative S2 of Nurchi (or its composition) in the method of Cho in treating glia tumor in a mammal, e.g. human. A person of ordinary skill in the art would have been motivated to derive similar or better therapeutic benefits in relation to the koji derivatives of Cho. Thus claims 1-2, 4-6 would have been obvious over the combined teachings of Nurchi and Cho. As to claim 7, Cho teach that the kojic acid derivatives can be used for treating glioma in children and the formulated food includes infant food, formulated milk. Hence a skilled artisan would have found it obvious to formulate the composition for pediatrics. As to claims 8-12, 17 the reference teaches the composition can be formulated for rapid or delayed release with the active ingredient, as a pharmaceutical composition, with excipients and carriers, e.g. lactose. Hence a skilled artisan would have found it obvious to formulate a pharmaceutical composition, for rapid or delayed release, with carriers e.g. lactose and in dosage forms such as tablets to provide a formulated dosage form with appropriate release. As to claims 15-16 18, Cho teach that the composition comprising kojic acid derivatives can be formulated as food, food additive, infant food, drinks etc. A person skilled in the art would have found it obvious to provide a pharmaceutically effective amount of compound of L1 in treating glioma tumor in a subject in the range of 0.5-5 mg/kg as claimed because Cho teach the pharmaceutically effective amount of the kojic acid derivative can range from 0.5-100 mg/day/kg. Thus claim 19 would have been obvious over the combined prior art teachings.
Claims 13, 14 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Nurchi et al. (IDS: J of Inorganic Biochemistry, 2018) in view of Cho et al. (KR 20110054448 A, See English translation) and further in view of Aparicio-Blanco et al. (International Journal of Pharmaceutics 581 (2020) 119283).
Nurchi and Cho teachings as discussed above. The rejections are incorporated herein. The above references do not teach the additional tumor agent in the method or in the formulation as claimed.
Aparicio-Blanco disclose glioblastoma chemotherapeutic agents that include cisplatin, oxaliplatin, cetuximab etc. in preclinical studies with nanomedicine-based drug delivery strategies tested in orthotopic animal models of glioma (see Table 1).
A person skilled in the art before the effective filing date of the invention would have found it obvious to add additional anti-tumor agent to the compound L1 in the formulation or in the method of treating glioma from Aparicio-Blanco’s teachings. A person skilled in the art would have been motivated to do so to obtain synergistic or additive therapeutic benefits in the treatment of glioma tumor in the individual. Thus claims 13-14, 20 would have been obvious over the combined prior art teachings.
Conclusion
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/Umamaheswari Ramachandran/Primary Examiner, Art Unit 1627