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 instant application is a 371 of PCT/IN2023/050301, filed on 03/29/2023. The instant application claims foreign priority to IN202231018911, filed on 03/30/2022.
Status of the Claims
Per Applicant’s amendment to the claims, submitted on 09/30/2024, claims 1 and 10 are amended, and claims 12-15 are newly added. Currently, claims 1-15 are pending in the instant application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/30/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Specification [037] line 8 contains a web address:
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Specification page 22 contains a web address in citation 11:
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Claim Objections
Claim 3 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112 – Second Paragraph
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 4-7, 8-15 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 2 is indefinite for reciting “wherein the inhibitor of glutamine synthetase enzyme is in the range of 50 µM to 2 mM in in vitro Plasmodium falciparum cultures and shall be present in the range of 0.1-100 mg/kg of the total body weight in the pharmaceutical composition”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Parent claim 1 is directed to a composition comprising an inhibitor of glutamine synthetase enzyme and artemisinin or dihydroartemisinin. Claim 1 does not recite any inclusion of plasmodium falciparum cultures, and does not recite any limitations relating to a subject or body weight. Accordingly, the instant claim provides improper antecedence. Furthermore, the instant claim appears to be related to in vitro and in vivo dosing amounts, which in the context of the parent claim would not be readily applicable.
Claim 4 is indefinite for reciting “wherein the inhibitor of glutamine synthetase irreversibly inhibits glutamine synthetase activity leading to a decrease in the production of asparagine and protein synthesis”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The instant claim does not provide a structural limitation applicable to its parent claim. Instead, the instant claim recites an intended use of the composition of claim 1 or the result of administering a composition of claim 1. Accordingly, the instant claim is not further limiting of its parent claim. See MPEP 2111.04:
In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a "‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted 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.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
Claim 5 is indefinite for reciting the term “providing”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The term “providing” is unclear because it has no standard definition in the art as opposed to a term such as “administering”. Furthermore, the claim does not recite any target subject for the composition to be provided to. This creates uncertainty as to whether the composition is being administered to plasmodium falciparum itself (i.e., in the form of cell cultures or otherwise) or to a subject having a plasmodium falciparum infection/infestation.
Claim 6 is indefinite for reciting “wherein the inhibitor of glutamine synthetase enzyme is in the range of 50 µM to 2 mM in in vitro Plasmodium falciparum cultures and shall be present in the range of 0.1-100 mg/kg of the total body weight in the pharmaceutical composition”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The parent claim to which the instant claim depends upon does not recite administration to a plasmodium falciparum culture or administration to any subject having a body weight. Accordingly, the instant claim provides improper antecedence.
Claim 7 is indefinite for the same reasons as claim 5. Claim 7 inherits the limitations of claim 5 and does not ameliorate the previously indicated issues.
Claim 8 is indefinite for reciting “wherein the inhibitor of glutamine synthetase irreversibly inhibits glutamine synthetase activity leading to a decrease in the production of asparagine and protein synthesis”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The instant claim does not provide a structural limitation applicable to the method of the parent claim. Instead, the instant claim simply recites the intended result of carrying out the method of claim 5, or a natural property of the glutamine synthetase inhibitor recited in the parent claim. Accordingly, the instant claim is not further limiting of its parent claim. See MPEP 2111.04.
Claim 9 is indefinite for reciting the term “combating”, because a person of ordinary skill in the art would not reasonably understand the metes and bounds of the claim. The term “combating” is not a standardized or recognized term in the art as opposed to terms such as “treating” or “reducing”. Accordingly, the instant claim in regard to “combating artemisinin resistance” is not understandable. Furthermore, the instant claim does not recite a subject to be treated (i.e., a subject having artemisinin resistant malaria, etc.).
Claim 9 is indefinite for reciting “and/or other antimalarials”, because a person of ordinary skill in the art would not reasonably understand the metes and bounds of the claim. The indicated recitation alongside the recitation of “existing artemisinin-based combination therapies” is indefinite because it is unclear what other antimalarials and combinations thereof would be included in the instant claim.
Claim 9 is indefinite for reciting “using glutamine synthetase inhibitors as claimed in claim 1”, because a person of ordinary skill in the art would not reasonably understand the metes and bounds of the claim. Firstly, the term “using” is ambiguous, and does not sufficiently describe the method in such a way that a person of ordinary skill in the art would be able to carry out the described process. Secondly, parent claim 1 to which the instant claim depends upon does not claim glutamine synthetase inhibitors, but a composition comprising glutamine synthetase inhibitors. Accordingly, the instant claim provides improper antecedence to claim 1, and it is unclear if the instant claim seeks to claim a method of use of a combination of the composition of claim 1 with artemisinin based therapies, or a combination of glutamine synthetase inhibitors with artemisinin based therapies.
Claim 10 is rejected for reciting “Glutamine Synthetase inhibitors for use in the method of suppressing the growth of Plasmodium falciparum”, because a person of ordinary skill in the art would not reasonably understand the metes and bounds of the claim. The instant claim is considered as a “use” claim and is not directed to a process, machine, manufacture, or composition. It is unclear how glutamine synthetase inhibitors are being “used” in the context of parent claim 5. Furthermore, claim 5 already recites the pharmaceutical composition of claim 1 which comprises a glutamine synthetase inhibitor. Accordingly, the instant claim is not further limiting of claim 5.
Claim 11 is indefinite for attempting to further limit a claim that is itself not further limiting of its parent claim. This rejection may be overcome by amending dependence to claim 5 in order to further limit the glutamine synthetase inhibitor, however, Applicant is warned that doing so would create a duplicate to claim 7.
Claim 12 is rejected for reciting “Glutamine Synthetase inhibitors for use in the method of suppressing the growth of Plasmodium falciparum”, because a person of ordinary skill in the art would not reasonably understand the metes and bounds of the claim. The instant claim is considered as a “use” claim and is not directed to a process, machine, manufacture, or composition. It is also unclear how glutamine synthetase inhibitors are being “used” in the context of parent claim 6. Accordingly, the instant claim also fails to further limit its parent claim.
Claim 13 is rejected for reciting “Glutamine Synthetase inhibitors for use in the method of suppressing the growth of Plasmodium falciparum”, because a person of ordinary skill in the art would not reasonably understand the metes and bounds of the claim. The instant claim is considered as a “use” claim and is not directed to a process, machine, manufacture, or composition. It is also unclear how glutamine synthetase inhibitors are being “used” in the context of parent claim 7. Accordingly, the instant claim also fails to further limit its parent claim.
Claim 14 is rejected for reciting “Glutamine Synthetase inhibitors for use in the method of suppressing the growth of Plasmodium falciparum”, because a person of ordinary skill in the art would not reasonably understand the metes and bounds of the claim. The instant claim is considered as a “use” claim and is not directed to a process, machine, manufacture, or composition. It is also unclear how glutamine synthetase inhibitors are being “used” in the context of parent claim 8. Accordingly, the instant claim also fails to further limit its parent claim.
Claim 15 is rejected for reciting “Glutamine Synthetase inhibitors for use in the method of suppressing the growth of Plasmodium falciparum”, because a person of ordinary skill in the art would not reasonably understand the metes and bounds of the claim. The instant claim is considered as a “use” claim and is not directed to a process, machine, manufacture, or composition. It is also unclear how glutamine synthetase inhibitors are being “used” in the context of parent claim 9. Accordingly, the instant claim also fails to further limit its parent claim.
Claim Rejections - 35 USC § 112 – First Paragraph
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 1 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 a composition comprising (i) L-methionine sulfoximine or phosphinothricin and (ii) artemisinin or dihydroartemisinin, does not reasonably provide enablement for a combination of (i) any inhibitor of glutamine synthetase and (ii) artemisinin or dihydroartemisinin. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make use of the invention commensurate in scope with these claims.
Claim 1 recites a composition comprising:
An inhibitor of glutamine synthetase enzyme
Artemisinin or dihydroartemisinin
A person of ordinary skill in the art would not reasonably be able to make use of the invention without undue experimentation. The recitation of “[a]n inhibitor of glutamine synthetase enzyme” could encompass any number of compounds having the function or ability to inhibit glutamine synthetase. Looking towards Applicant’s disclosure for guidance, specification pages 9-21 provide working Examples 1-11. In the working examples, it appears that the only glutamine synthetase inhibitors tested were L-methionine sulfoximine (MSO) and phosphinothricin (PPT). While the working examples establish support for the aforementioned inhibitors, it does not support the use of any and all compounds capable of inhibiting glutamine synthetase. The claim as currently recited would require a person of ordinary skill in the art to test all compounds with the aforementioned inhibiting capability together with artemisinin or dihydroartemisinin to make use of the invention.
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.
Claim(s) 1 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gordon (PNAS October 20, 2015 vol. 112 no. 42 13075–13080) in view of Chen (Chinese Medical Journal, 107(9); 709-711, 1994).
Claim 1 recites a pharmaceutical composition for combating drug resistance in plasmodium falciparum, the composition comprising:
An inhibitor of glutamine synthetase enzyme
Artemisinin or dihydroartemisinin
Firstly, it must be established that the recitation of “combating drug resistance in plasmodium falciparum” does not hold patentable weight because it is directed to an intended use of the claimed composition and does not provide structural limitation.
Gordon teaches the use of 6-diazo-5-oxo-L-norleucine (DON) for the treatment of cerebral malaria. Gordon indicates that human cerebral malaria is a complication of plasmodium falciparum infection (page 13075)1 and further indicates that DON is an inhibitor of glutamine synthetase (page 13076)2. In order to mimic conditions of human cerebral malaria, Gordon induces experimental cerebral malaria (a model of human cerebral malaria) in mice by infecting them with plasmodium berghei (page 13075)3. Treatment of said animals with DON was found by Gordon to be effective in decreasing BBB disfunction, decreasing brain swelling, decreasing T cell degranulation and accumulation in the brain, and reversal of metabolic changes associated with the disease (page 13079)4.
While Gordon teaches the use of DON as a glutamine synthetase inhibitor for the treatment of cerebral malaria caused by p.falciparum infection, they do not explicitly teach combination with artemisinin or dihydroartemisinin. However, it would have been obvious for a person of ordinary skill in the art to utilize DON in combination with artemisinin, because Chen teaches the use of artemisinin for treatment of p.falciparum infection, and there would be a reasonable expectation that a composition comprising such a combination would be successful in treating cerebral malaria caused by p.falciparum infection.
Chen teaches the treatment of patients having gametocytes of p.falciparum by administration with artemisinin. In particular, patients were divided into three groups, wherein one group (Group A) administered 1200 mg artemisinin daily for 5 days. Chen indicates that these Group A patients, as a result of administration, saw significantly decreased gametocyte density, infectivity, and infective rate to mosquitoes (page 710-711)5. The results of testing are provided in the graphs below (Fig. 1 and Fig. 2):
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Given that Gordon teaches the use DON as a glutamate synthetase inhibitor to treat human cerebral malaria brought on by p.falciparum infection, and Chen teaches the use of artemisinin in order to treat p.falciparum infection, it would have been prima facie obvious for a person of ordinary skill to develop a composition comprising both DON and artemisinin, as there would have been reasonable expectation that such a composition would be effective in treating a patient having both p.falciparum infection and cerebral malaria.
Allowable Subject Matter
While the none of the claims of the instant application are in condition for allowance, the claims describe certain subject matter that may be allowable. More specifically, the combination of l-methionine sulfoximine or phosphinothricin with artemisinin or dihydroartemisinin, and methods of use thereof. Said combination being described in claim 3. However, claim 3 is not in condition for allowance and is objected to for being dependent upon a previously rejected claim.
Conclusion
Claims 1-2 and 4-15 are rejected.
Claim 3 is objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIC TRAN whose telephone number is (571)272-7854. The examiner can normally be reached Mon-Fri 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached at (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERIC TRAN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 “One of the most deadly complications of P. falciparum infection in humans is cerebral malaria (HCM) characterized by the onset of severe neurological signs such as altered consciousness, seizures, and coma (2).”
2 “DON broadly inhibits Gln metabolism, in part by blocking Gln transport and inhibiting all three isoforms of glutaminase as well as other Gln-using enzymes such as the aminotransferases and glutamine synthetase (24).”
3 “Experimental cerebral malaria (ECM) in mice is a widely used model of HCM and provides a valuable tool for elucidating the mechanisms involved in CM pathogenesis and identifying cellular and molecular targets for adjunctive therapy (7). In ECM, 6–7 d after infection with Plasmodium berghei ANKA (PbA), mice of susceptible strains, such as C57BL/6, develop ataxia, paralysis, seizures, and coma and ultimately die (8). ECM displays key features of HCM, including BBB breakdown, focal hemorrhaging, and brain swelling (9–11).ECM’s pathology also requires sequestration of iRBCs in the brain vasculature (12), a hallmark of HCM (3).”
4 “This clinical response was accompanied by the ability of DON to inhibit pathology as measured by decreases in BBB dysfunction, brain swelling, and degranulation of parasite-specific CD8+ T cells that accumulated in the brain. Further-more, DON is able to reverse or prevent metabolic changes associated with the disease state.”
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