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 on 9/27/2024. Claims 1-10 have been cancelled. Claims 11-30 are pending and are examined based on the merits herein.
Application Priority
This application filed 07/25/2024 is a Continuation of 17738181, filed 05/06/2022, now U.S. 12076304, 17738181 is a Continuation of 16839899, filed 04/03/2020.
Information Disclosure Statement
The information disclosure statement(s) (IDS) filed on 9/27/2024 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 11-30 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 anticoagulant and antithrombotic effects with 15-HEPE (Figs. 38-39, Tables 38-39) does not reasonably provide enablement for preventing blood clotting or a venous thromboembolism in a subject in need thereof, the method comprising administering to the subject 15- HEPE or its composition. 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.
The instant specification fails to provide information that would allow the skilled artisan to practice the prevention of blood clotting or a venous thromboembolism with said 15-HEPE or its composition.
To be enabling, the specification of the patent 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 (Fed. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).1
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) the nature of the invention,
2) the state of the prior art,
3) the relative skill of those in the art,
4) the breadth of the claims,
5) the predictability of the art,
6) the amount of direction or guidance provided,
7) the presence or absence of working examples and
8) the quantity of experimentation necessary
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
(1),(2),(3): The nature of the invention, state and relative skill level:
The invention relates to a method of treating and/or preventing blood clotting or treating or preventing the venous thromboembolism in a subject in need thereof, the method comprising administering to the subject 15-hydroxyeicosapentaenoic acid (15- HEPE) or a composition comprising 15-HEPE, wherein administering the composition has an anticoagulant and/or antithrombotic effect.
The instant specification teach “Hematologic disorders include red blood cell disorders and thrombophilia”. Thrombophilia is a class of disorders that increase a subject’s risk of developing blood clots in veins and arteries. These clots can break loose from the blood vessel and travel through the blood stream to an organ thereby preventing blood flow to that organ resulting in ischemia. These conditions lead to an increased risk of stroke and/or pulmonary embolism [0004].
According to Cleveland Clinic, “A blood clotting disorder is a condition that makes your body more likely than normal to make blood clots. You can inherit or acquire one of these conditions” (p 1, para 1). A blood clotting disorder makes your blood form clots too easily. This is also called a hypercoagulable state or thrombophilia (See p 1, para 2). The article also lists inherited hypercoagulable and acquired conditions (See p 2, last para, p 3, para 1) and treatments (p 4, last para). The reference is explicit in teaching that “If you’re born with an inherited form of blood clotting disorder, you can’t prevent it. Still, that doesn’t mean you’re going to get a blood clot” (See page 6 under Prevention). (Cleveland Clinic, 2026, https://my.clevelandclinic.org/health/diseases/16788-blood-clotting-disorders-hypercoagulable-states)
Johns Hopkins teaches regarding the blood clot treatment that include blood thinning medications, catheter directed treatments, surgical thrombectomy etc. (See p 1, Johns Hopkins Medicine, https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/blood-clot-treatment, 2026).
According to CDC, Venous thromboembolism (VTE) is a term referring to blood clots in the veins (See Overview). The reference teach that almost anyone can have a DVT/PE and lists the risk factors that increases the development of such conditions(see Risk Factors). Also provided some tips that can help prevent DVT/PE (See Prevention). However there is no certainty that treatment or exercises would prevent blood clot from occurring.
As illustrative of the state of the art, the examiner cites the fact that nowhere in the specification did applicant demonstrate prevention of blood clotting or venous thromboembolism. Moreover, given that blood clotting can be inherited, diseases are characterized by genetic factors that cannot be prevented, the examiner maintains that absent demonstration from applicant demonstrating actual prevention of said disease one would not be able to ascertain if indeed said prevention occurs. Given that applicant has yet to demonstrate prevention of any disease, the examiner maintains that applicant has not enabled the breadth of the claims.
The relative skill of those in the art is high, that of an MD or PHD.
(4) The breadth of the claims:
The claims are limited in scope to treating blood clots with 15-HEPE
(5) Predictability of the art:
Despite the advanced training of practitioners in the art, it is still impossible to predict from the specification and prior art that 15-HEPE will prevent the blood clot from occurring in a subject or prevent from occurring again after treatment. For example long term treatment may be necessary or required to reduce the frequency of the occurrence of blood clots.
Prevention requires the recited method to be completely effective in all patients at all times. It is respectfully pointed out that a method of preventing the diseases or disorders claimed means that the compounds or compositions are administered to subjects that do not have such diseases or disorders. The purpose is to prevent the condition before occurring but not to treat after it has occurred. Slowing or reducing the disease or disorder associated with red blood cell disorders is possible but not complete prevention of such conditions.
Furthermore, the definition of "to prevent" and the “act of preventing" embraces the complete 100% inhibition. Thus, the burden of enablement in the assertion of this claim is much higher than would be the case of enabling the treatment of the condition and is not achieved.
It is well established that "the scope of enablement various inversely with the degree of unpredictability of the factors involved," and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839 (1970).
Absent a mechanistic link between the method steps and the observed effect, the pharmaceutical and medical treatment arts are highly unpredictable. Most progress is established through empirical and anecdotal evidence as to the efficacy of certain treatments. Once a mechanistic link has been established between the method and the mechanism of action become more predictable. However, many uncertainties can still exist even when the mechanism of action is known. For example, factors such as the bioavailability, pharmacokinetic profile, and potency of a compound can still be uncertain even if it can be expected to be active in disease models. It is highly unpredictable to prevent the blood clot disorder with 15-HEPE as claimed.
(6)/(7) The amount of direction or guidance provided and the presence or absence of working examples:
The specification provides no direction or guidance for prevention of any disease let alone prevention of blood clot disorder. No reasonably specific guidance is provided concerning useful therapeutic protocols for preventing any disease, other than effects of 15-HEPE in fibrosis, and/or NAFLD, change in red blood cell count, red blood cell distribution and reticulocyte count (fig. 38A-C) with 15-(s)-HEPE, change in prothrombin time, activated partial thromboplastin time, fibrinogen (Table 39). (See Figs. 1-39C). There is no evidence in the specification that 15-HEPE was administered to a subject and prevention occurred.
(8) The quantity of experimentation necessary:
Because of the known unpredictability of the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion that the instantly claimed 15-HEPE could be predictably used for preventing blood clots as inferred by the claims and contemplated by the specification. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
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.
Claims 11-17, 19-30 are rejected under 35 U.S.C. 103 as being unpatentable over Rowe et al. (Applicants cited IDS: WO 2014/019919) and Wun (Sickle Cell Disease, Am Soc Hematology, 2016, 640-647).
Rowe teaches pharmaceutical compositions comprising 15-OHEPA (which is 15-HEPE), its use in treating disorders. Rowe provides a pharmaceutical composition comprising 15-hydroxy eicosapentaenoic acid (known as 15-OHEPA or 15-HEPE) and this may be for oral administration (See Abstract, page 1-Summary, lines 1-2). In some embodiments, the 15-OHEPA is in the form of a C1 -4 alkyl ester such as methyl ester or ethyl ester (p 1, summary, para 1, also p 3, lines 23-29).
Rowe explicitly teach that the disease that can be treated with 15-HEPE include sickle cell disease (see page 13, line 21). Further taught is that cardiovascular symptoms associated with sickle cell disease are ameliorated (See p 25, last para, lines 1-2). Rowe teaches effective amount refers to the amount of an active composition that is required to confer a therapeutic effect on the subject and a "therapeutically effective amount," refers to a sufficient amount of an agent or a compound being administered which will relieve to some extent one or more of the symptoms of the disease, disorder, or condition being treated (See p 14, para 1, lines 1-5). Further taught is that increase in RBC (red blood cells) is at least about 5%-400% compared to base line or placebo arm (p 20, (v), para 6).
Rowe teaches that the invention provides pharmaceutical compositions, for example orally deliverable compositions, comprising 15-OHEPA, about 0.1 % to about 99%, about 1 % to about 95%, about 5% to about 90% by weight of 15-OHEPA (See p 3, last para bridging page 4). Rowe teaches that the dosage forms include oral dosage form (p 7, last para) and includes tablets, capsules etc. (p 8, first para). The composition provides a daily dose of 15-OHEPA in an amount of about 1-10,000 mg (See p 25, para 2, lines 1-2).The composition of 15-OHEPA is present in an amount of about 50 mg to about 1000 mg (page 2, lines 3-6, claim 5). The reference also teaches that if a subject is administered 1-4 g of 15-OHEPA a day this may be up to 4 capsules each providing 1g of 15-OHEPA (page 8, para 4).
Wun teach that sickle cell disease is an inherited thrombophilia (see title). Further taught is that venous thromboembolism (VTE: deep venous thrombosis and pulmonary
embolism) has been until recently an underappreciated complication of sickle cell disease, with incident event and recurrence rates consistent with a strong thrombophilia (Abstract). It is noted that deep venous thrombosis (DVT) or pulmonary embolism (PE) were diagnosed in patients with SCD; cerebral vein thrombosis and deep venous thrombosis were much more common among women with SCD (See p 643, col. 2, para 2, p 644, col. 2, para 2, Table 4).
From the teachings of Rowe, a person of ordinary skill in the art before the effective filing date of the invention would have found it obvious to administer 15-HEPE or its composition to a subject with sickle cell disease. Wun teach that thrombophilia, venous thromboembolism are associated with sickle cell disease patients. A person of ordinary skill in the art would have been motivated to administer 15-HEPE or its composition to a subject with sickle cell disease to provide therapeutic benefits to the subject. Thus, administration of the same active agent, 15-HEPE to subjects with sickle cell disease wherein thrombophilia, venous thromboembolism are associated with SCD, would result in the treatment of the blood clot and VTE. As to the limitation of wherein administering the composition has an anticoagulant or antithrombotic effect, it is noted that it is the inherent property of the composition when administered to the same set of subjects as claimed (subject in need thereof, e.g. sickle cell). Thus claims 11, 15, 16-17, 19, 21, 25-27 are addressed. As to claims 12-13, 23, 24, 29-30, these are the effects of administering to the subject for e.g. sickle cell disease with the same therapeutic agent, 15-HEPE from the teachings of the prior art. As to claims 14, 22, from Rowe a skilled artisan would have found it obvious to administer 8 mg of 15-HEPE as the reference teaches administration for e.g. 1-10 g. As to claim 20, the limitations are to the characteristics of the hematological disorder. As to claim 28, Rowe’s teaches treating sickle cell disease subjects and accordingly the patient (subject) will necessarily have all the experiences that is claimed.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Rowe et al. (Applicants cited IDS: WO 2014/019919) and Wun (Am Soc of Hematology, p 640-647, 2016) in view of Schultz (Am J of Hematology, 74, 249-253).
Rowe and Wun teachings as above.
The above art is not explicit in teaching that the subject has an hematological disorder of blood cancer.
Schultz teach pediatric patients having sickle cell disease and leukemia (see Abstract). The reference teaches malignancy in patients with sickle disease has been reported and patients have leukemia, solid tumors etc. (abstract).
A person of ordinary skill in the art before the effective filing date of the invention would have found it obvious from Schultz that a subject with a sickle cell disease also have leukemia is a subject. In other words the instantly claimed patient population include such patients. Hence a skilled artisan would have been motivated to treat such select sub population of sickle cell patients to provide therapeutic effects in regards to blood clots or associated thrombophilia with a reasonable expectation of success. Thus claim 18 would have been obvious over the combined prior art teachings.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to UMAMAHESWARI RAMACHANDRAN whose telephone number is (571)272-9926. The examiner can normally be reached M-F- 8:30-5:00 PM (PST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached at 5712705239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Umamaheswari Ramachandran/ Primary Examiner, Art Unit 1627
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