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 .
Priority
The present application claims status as a 371 (National Stage) of PCT/KR2021/019660 filed December 22, 2021; and claims priority under 119(a)-(d) to Korean Application No. KR10-2020-0180640 filed on December 22, 2020.
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d) for Korean Application No. KR10-2020-0180640, which papers have been placed of record in the file. Please note that the application is in Korean and thus cannot be verified.
Claim Status
Claims 1-11 were originally filed and amended on 06/21/2023. The amendment cancelled claims 6-11 and amended claims 1-5.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 06/21/2023, 10/18/2024 and 11/12/2024 have been considered by the Examiner.
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.
2. Claims 1-5 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. Claim 1 recites the limitation "an individual in need of treatment" in line 4. There is insufficient antecedent basis for this limitation in the claim. Although claim 1 is directed to a method of treating alcoholic and non-alcoholic fatty liver disease, the claim fails to recite a connection between the diseases being treated (i.e., alcoholic and non-alcoholic fatty liver disease) and the individual in need of treatment. Since the phrase “an individual in need of treatment” encompasses any individual, not necessarily affected by the diseases of interest (i.e., alcoholic and non-alcoholic fatty liver disease), thus an ordinary skilled artisan would not be able to ascertain the metes and bounds of the claimed method with respect to the subject population to which the method of treatment would be administered to. Subsequently, claims 2-5 are also rejected because they are dependent upon a rejected claim and because it is unclear whether the limitations recited in claims 2-5 (i.e., hepatocyte protection, suppression in blood lipid concentration, suppression of lipid accumulation in liver tissue, and suppression of liver fibrosis) are related to the target diseases to be treated (i.e., alcoholic and non-alcoholic fatty liver disease) or to any other condition that affects an individual in need of treatment (i.e., any individual in need of any treatment). Therefore, in order to advance prosecution, the Examiner is interpreting the phrase “an individual in need of treatment” as an individual needed to be treated for alcoholic or non-alcoholic fatty liver disease.
3. Claim 2 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. In the instant case, the claim recites that the “pharmaceutical composition protects hepatocytes from toxicity caused by alcohol.” However, parent claim 1 recites treating alcoholic and non-alcoholic fatty liver disease, therefore it is unclear and/or ambiguous as to how the pharmaceutical composition protects hepatocytes from toxicity caused by alcohol in non-alcoholic fatty liver disease. Additionally, it is unclear and/or ambiguous as to how the claimed pharmaceutical composition protects hepatocytes that already have been damaged/compromised due to toxicity caused by alcohol (i.e., an individual in need of treatment for alcoholic fatty liver disease). Therefore, claim 2 is indefinite because an ordinary skilled artisan would not be able to ascertain whether the claimed pharmaceutical composition protects hepatocytes from toxicity caused by alcohol in an individual in need of treatment for non-alcoholic fatty liver disease, nor how the claimed pharmaceutical composition protects hepatocytes from toxicity in an individual whose hepatocytes have already been damaged due to toxicity caused by alcohol. Additionally, it has not been clearly stablished whether claimed pharmaceutical composition protects hepatocytes from toxicity caused by alcohol in an individual that already has the hepatocytes compromised due to non-alcoholic fatty liver disease, or whether the claimed composition protects hepatocytes from toxicity caused by alcohol in an individual who is not affected by non-alcoholic fatty liver disease.
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.
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness
(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
4. Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over US 2015/0065556 A1 Pub Date: March 5th 2015 (cited in the IDS filed on 06/21/2023) (herein after “Birsoy et al.”) as evidenced by Manzo-Avalos et al., Int. J. Environ. Res. Public Health. 2010, 7, pp. 4281-4304 (herein after “Manzo-Avalos et al.”).
Regarding claim 1, Birsoy et al.’s invention pertains to a method treating a mammalian subject in need of treatment for a mitochondrial disorder, the method comprising administering an ATPIF1 inhibitor to the subject, wherein the mitochondrial disorder is characterized by liver disfunction (see pg. 8, para[0028]). Birsoy et al. add that a mitochondrial disorder is a hepatic disorder which refers to any disorder that affects the structure and function of the liver, e.g., any disorder in which death or dysfunction of liver cells ( e.g., hepatocytes) occurs (see pg. 40, para[0212]). Mitochondrial dysfunction is a major mechanism of liver injury and plays a role several acute and chronic hepatic disorders such as alcoholic and non-alcoholic fatty liver disease (NAFLD), drug-induced steatohepatitis, viral hepatitis, biliary cirrhosis, ischemia/reperfusion injury, and transplant rejection (see pg. 40, para[0212]). Hepatic disorders include those induced by drugs (e.g., acetaminophen), toxins (e.g., alcohol), and hepatotropic viruses (e.g., hepatitis B or C virus, among others) (see pg. 40, para[0212]). Hepatic inflammation and fibrosis are a prominent component of many chronic liver disorders (see pg. 40, para[0212]). Thus, Birsoy et al.’s invention constitutes a method for treating alcoholic and non-alcoholic fatty liver disease as recited in instant claim 1.
Birsoy et al.’s invention provides a pharmaceutical composition comprising an ATPIF1 inhibitor (see pg. 9, para[0029]), wherein suitable preparations, e.g., substantially pure preparations of an active agent (i.e., an ATPIF1 inhibitor) may be combined with one or more pharmaceutically acceptable carriers or excipients and the pharmaceutical carrier or excipient does not significantly interfere with the biological activity or effectiveness of the active ingredient (see pg. 62, para[0355]). Thereby, the teachings of Birsoy et al. constitute administering a pharmaceutical composition comprising ATPase inhibitory factor 1 (IF1) as an active ingredient to an individual in need thereof as recited in instant claim 1.
Regarding claims 2-5, Birsoy et al.’s teach that loss of function of ATPIF1 confers protection against a variety of mitochondrial poisons (see pg. 44, para[0239]). Birsoy et al. inhibiting ATPIF1 in at least some cell of a subject increases resistance of the cells to a mitochondrial poison (see pg. 46, para[0245]). Thus Birsoy et al.’s methods reduce the likelihood of a cell or subject to experience deleterious effects (e.g., cell death or damage) due to a mitochondrial poison or reduce the severity of such effects (see pg. 45, para[0245]). Birsoy et al. also define “mitochondrial poison” as an agent that inhibits at least one mitochondrial function, reduces the average number of mitochondria per cell, and/or causes an abnormality in mitochondrial structure (see pg. 14, para[0062]).
As evidenced by Manzo-Avalos et al., ethanol produces alterations in the mitochondrial structure and function of several organs, including liver, and heart, both in laboratory animals and humans (see pg. 4185, second paragraph). These changes affect the mitochondrial function decreasing respiratory rates and ATP levels, and might result in increased production of reactive oxygen species (ROS) (see pg. 4185, second paragraph).
As previously discussed, Birsoy et al. teach a method of treating a mammalian subject in need of treatment for a mitochondrial disorder, wherein the mitochondrial disorder is a hepatic disorder induced by toxins (e.g., alcohol), comprising administering an ATPIF1 inhibitor to the subject. Since alcohol is a “mitochondrial poison” according to Birsoy et al.’s definition, and since Birsoy et al.’s methods reduce the likelihood of a cell or subject to experience deleterious effects (e.g., cell death or damage) due to a mitochondrial poison or reduce the severity of such effects; it must follow that a pharmaceutical composition comprising ATPIF1 protects hepatocytes from toxicity caused by alcohol as recited in instant claim 2.
Birsoy et al. also teach testing ATPIF1 inhibitor in animal model of GRACILE Syndrome (see pg. 72, para[0454]), wherein mice harboring a homozygous Bcs1l 232A>G mutation are treated starting at birth or starting at 2 or 4 weeks after birth with an siRNA that inhibits ATPIF1 and are monitored for symptoms similar to those found in the human GRACILE syndrome, i.e., growth failure, hepatic glycogen depletion, steatosis, fibrosis, and cirrhosis, as well as tubulopathy complex III deficiency, lactacidosis (see pg. 72, para[0454]). Birsoy et al. report a reduction in incidence and/or severity of symptoms and/or an increased lifespan in any of the treated groups as compared with untreated controls confirms the usefulness of ATPIF1 inhibition as a therapeutic strategy (see pg. 72, para[0454]). Thus, since Birsoy et al.’s ATPIF1 reduces the incidence and/or severity of symptoms such as steatosis (i.e., the accumulation of excess fat in liver cells) and fibrosis, then it must follow that the claimed pharmaceutical composition comprising ATPIF1 suppresses lipid accumulation in liver tissue and suppresses liver fibrosis, as recited in instant claims 4-5.
Additionally, the court has found that the determination of whether clauses such as “wherein” and “whereby" is a limitation in a claim is dependent on the specific facts of the case. If the “wherein" or “whereby” clause limits a process claim where the clause gives meaning and purpose to the manipulative steps, it should be given patentable weight. However, the court also found (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” In the instant case wherein the pharmaceutical composition: protects hepatocytes from toxicity caused by alcohol, suppresses an increase in blood lipid concentration, suppresses lipid accumulation in liver tissue, and suppresses liver fibrosis, as recited in instant claims 2-5, respectively; are intended inherent results of administering a pharmaceutical composition comprising ATPase inhibitory factor 1 (IF1) as an active ingredient to an individual in need thereof. Accordingly, claims 2-5 recite intended results that do not appear to render material to patentability.
MPEP 2112-2112.02 also states that when a reference discloses all the limitations of a claim except for a property or function, and the Examiner cannot determine whether or not the reference inherently possesses properties which anticipate or render obvious the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, Birsoy et al. teach pharmaceutical compositions comprising ATPIF1 inhibitor as an active agent and report that inhibiting ATPIF1 in at least some cell of a subject increases resistance of the cells to a mitochondrial poison. Additionally that the methods reduce the likelihood of a cell or subject to experience deleterious effects (e.g., cell death or damage) due to a mitochondrial poison or reduce the severity of such effects, and that reduction in incidence and/or severity of symptoms such as steatosis and fibroses were observed in treated groups as compared with untreated controls thus confirming the usefulness of ATPIF1 inhibition as a therapeutic strategy. The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not a pharmaceutical composition comprising ATPIF1 as an active ingredient protects hepatocytes from toxicity caused by alcohol, suppresses an increase in blood lipid concentration, suppresses lipid accumulation in liver tissue, and suppresses liver fibrosis, as recited in instant claims 2-5. The cited art taken as a whole demonstrates a reasonable probability that a method treating a mammalian subject in need of treatment for a mitochondrial disorder, the method comprising administering an ATPIF1 inhibitor to the subject, wherein the mitochondrial disorder is characterized by liver disfunction is ether identical or sufficiently similar to the claimed protection of hepatocytes from toxicity caused by alcohol as recited in instant claim 2, suppression of an increase in blood lipid concentration as recited in instant claim 3, suppression of lipid accumulation in liver tissue as recited in instant claim 4, and suppression of liver fibrosis as recited in instant 5; and that whatever differences exists are not patentably significant. Therefore, with the showing of the reference, the burden of establishing novelty or non-obviousness by objective evidence is shifted to the Applicants.
From the teachings of the references, the Examiner recognizes that it would have been prima facie obvious to one of ordinary skill in the art to follow Birsoy et al.’s teachings in order to arrive at the instantly claimed method for treating alcoholic and non-alcoholic fatty liver disease comprising administering a pharmaceutical composition comprising ATPase inhibitory factor 1 (IF1) as an active ingredient to an individual in need thereof. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do it because ATPIF1 was known to confer protection against a variety of mitochondrial poisons; and because it was also known that a pharmaceutical composition comprising an ATPIF1 inhibitor reduce the likelihood of a cell or subject to experience deleterious effects (e.g., cell death or damage) due to a mitochondrial poison or reduce the severity of such effects. One of ordinary skill in the art would have had a reasonable expectation of success given that Birsoy et al.’s method of treating a mammalian subject in need of treatment for a mitochondrial disorder, wherein the mitochondrial disorder is a hepatic disorder induced by toxins (e.g., alcohol), comprising administering an ATPIF1 inhibitor to the subject; and given that administering an siRNA that inhibits ATPIF1 to animal model of GRACILE Syndrome reduce the incidence and/or severity of symptoms such as growth failure, hepatic glycogen depletion, steatosis, fibrosis, and cirrhosis, as well as tubulopathy complex III deficiency, lactacidosis and/or increased lifespan in any of the treated groups as compared with untreated controls, thus confirming the usefulness of ATPIF1 inhibition as a therapeutic strategy. Therefore, following Birsoy et al.’s teachings would support the instantly claimed method for treating alcoholic and non-alcoholic fatty liver disease, comprising administering a pharmaceutical composition comprising ATPIF1 as an active ingredient to an individual in need thereof by constituting Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention, pursuant to KSR.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
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/CLAUDIA ESPINOSA/ Patent Examiner, Art Unit 1654 /LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654