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 preliminary amendment filed 04/24/2023, amended claims 1-10.
Claims 1-10 are pending and examined on the merits herein.
Priority
This application claims the following priority:
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Claim Objections
Claims 1-2 and 5 are objected to because of the following informalities:
-In claim 1, the phrase “and a stereoisomer, an isotopically labeled compound, a solvate or a polymorph thereof or a pharmaceutically acceptable salt thereof,” should be replaced with - -or a stereoisomer, isotope, solvate, polymorph, or pharmaceutically acceptable salt thereof- -, for grammatical clarity and for the recitation of proper Markush language. See MPEP 2173.05(h) for guidance on proper Markush language.
For support in replacing the phrase “an isotopically labeled compound” with the term “isotope,” see pg. 4, lines 10-20, of the instant specification.
-In claim 2, the phrase “pharmaceutically acceptable salt is selected from the following structure,” should be and replaced with, - -sesquiterpene lactone compound is a pharmaceutically acceptable salt form having the following structure- -, since the structure does not depict the salt alone, but depicts a salt form of the sesquiterpene lactone compound, and since only a single structure is depicted.
-In claim 5, the term “the” prior to “proliferation” in line 3, should be deleted.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-10 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 "the subject" in line 2. There is insufficient antecedent basis for this limitation in the claim. It is not clear if “the subject” is any subject with “radiotherapy-induced injuries” or if Applicant’s reference to “the subject” is intended to further narrow the scope of a subject to “a subject with brain cancer undergoing radiotherapy,” for example.
In view of compact prosecution, for the purpose of applying prior art, “the subject” is interpreted as any subject undergoing radiotherapy.
-Claim 3 recites the limitation "the radiotherapy" in line 1. There is insufficient antecedent basis for this limitation in the claim. While claim 1, from which claim 3 depends, recites “radiotherapy-induced injuries” in the preamble, it does not recite administering radiotherapy as an active step.
Claim 3 is additionally indefinite, as it is not clear how radiotherapy, which is a treatment using ionizing radiation, comprises solid tumors and metastatic tumors. It is not clear if this is a typo and Applicant intended to recite a step of administering radiotherapy to solid or metastatic tumors, or if the radiotherapy somehow comprises solid tumor cells or metastatic tumor cells.
In view of compact prosecution, for the purpose of applying prior art, claim 3 is interpreted as “wherein radiotherapy is administered to solid tumors or metastatic tumors.”
-Regarding claim 4, the phrase "e.g., X-ray-induced radiation injuries and heavy ion radiation-induced radiation injuries" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase “e.g.” are part of the claimed invention, or merely exemplary of the claimed invention. See MPEP § 2173.05(d).
In view of compact prosecution, for the purpose of applying prior art, the information following “e.g.” is interpreted as exemplary and as not further limiting the claims.
-Claim 6 recites the limitation "the sesquiterpene lactone compound and pharmaceutically acceptable auxiliary materials" in lines 1-2. There is insufficient antecedent basis for “the. . .pharmaceutically acceptable auxiliary materials,” limitation in the claim.
In view of compact prosecution, for the purpose of applying prior art, this claim in interpreted as “wherein the sesquiterpene lactone compound is formulated into a medicament further comprising a pharmaceutically acceptable auxiliary material.”
All other claims not specifically recited are rejected for depending from an indefinite claim and failing to cure the deficiency.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over US 2022/0362275 to Newman (effectively filed 12/02/2019, PTO-892) in view of Xi (ACT001, a novel PAI-1 inhibitor, exerts synergistic effects in combination with cisplatin by inhibiting PI3K/AKT pathway in glioma, Cell Death and Disease, published 2019, IDS of 06/06/2023).
Newman teaches methods and compositions for treating glioblastoma (title, abstract).
Newman specifically teaches a combination protocol method for the treatment of glioblastoma comprising treating a subject with radiotherapy, treating a subject with chemotherapy, and treating a subject with pharmacotherapy, wherein temozolomide is taught as the chemotherapy (pg. 33, claims 2 and 8).
Regarding claim 1, while Newman teaches a method of treating glioblastoma by administering radiotherapy, temozolomide, and pharmacotherapy, it differs from that of instant claim 1 in that it does not teach the sesquiterpene lactone compound.
Xi teaches ACT001 as directly binding to PAI-1 to inhibit the P13K/AKT pathway, which induces the inhibition of glioma cell proliferation, invasion and migration (abstract). Xi teaches that ACT001, shows excellent results in controlling the growth of glioblastoma (GBM) (pg. 1, “Introduction). Xi further teaches the combination of ACT001 and cisplatin as having a synergistic effect on the inhibition of glioma in vitro and in vivo (abstract).
Xi teaches that GBM is the most common and most aggressive primary malignant brain tumor in adults and results in a high morbidity, high mortality and poor patient prognosis. Xi teaches that cisplatin has been used as a neoadjuvant therapy with temozolomide in malignant glioma therapy, and that the treatment of glioma urgently needs the development of new therapeutic drugs or the establishment of new combination therapies to improve patient survival and reduce the side effects of conventional chemotherapy (pg. 1 “Introduction”).
Xi teaches that the concentration of the best drug for the treatment of glioma, temozolomide, was only 0.4 times higher in the brain than that in the blood. In contrast, Xi teaches that the concentration of ACT001 is 1.8 times higher in the brain than in the blood (pg. 14, Col. 1, last full paragraph).
As evidenced by pg. 8 of the instant specification, ACT001 is:
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It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the temozolomide of Newman with ACT001 or a combination of ACT001 and cisplatin, to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Xi and Newman are both directed toward methods of treating glioblastoma,
- Xi teaches that ACT001, shows excellent results in controlling the growth of GBM,
-Xi teaches that the concentration of temozolomide in the brain was only 0.4 times higher than that in the blood, but that the concentration of ACT001 is 1.8 times higher in the brain than in the blood,
-Xi teaches the combination of ACT001 and cisplatin as having a synergistic effect on the inhibition of glioma in vitro and in vivo, and
-Xi teaches that the treatment of glioma urgently needs the development of new therapeutic drugs or the establishment of new combination therapies to improve patient survival and reduce the side effects of conventional chemotherapy.
As such, an ordinary skilled artisan would have been motivated to make such a substitution, to predictably arrive at a more potent and effective method of treating glioblastoma.
While, the combination of Newman and Xi does not explicitly teach “alleviation of radiotherapy-induced injury,” it teaches the same method of administering ACT001 to a subject in need thereof, i.e. a subject undergoing radiotherapy, in the same therapeutically effective amounts (it is noted that the instant specification teaches an amount of 200mg/kg of ACT001 (pgs. 17-18, specification), and Xi teaches an amount of 200mg/kg of ACT001 (pg. 5, Col. 1)), as that taught by the instant specification and claims. As such, the combined method of Newman and Xi would necessarily alleviate radiotherapy-induced injuries. See MPEP 2112.02.
Regarding claim 2, the ACT001 taught by Xi is
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Regarding claim 3, Newman teaches glioblastoma as a class of primary brain tumors and teaches its methods for the treatment of tumor cells, i.e. solid tumors (Fig. 1A; Fig. 2A; [0004]; [0005]; [0008]). And, as evidenced by pg. 5 of the instant specification, glioblastomas are solid tumors.
Regarding claim 4, Newman teaches radiotherapy and specifically teaches X-ray radiotherapy (pgs. 34-35, claims 8, 11, 13, 31).
Regarding claim 5, 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)).
While Xi does not explicitly teach the glioblastoma as metastatic, Xi teaches glioblastoma as one of the fastest growing tumors of the central nervous system and as the most aggressive and lethal form of primary brain cancer. As such, it is reasonable to assume that the patient population of Xi comprises patients with metastatic glioblastoma ([0005]), and it is reasonable to assume that a method of treating glioblastoma, in general, would treat metastatic glioblastoma.
Thus, in this case, the wherein clause expresses the desired result of the positive step of administering the instantly claimed sesquiterpene lactone compound to a subject treated with radiotherapy for a metastatic glioblastoma. As such, the combined method of Newman and Xi meet this limitation.
Regarding claim 6, the combination of Newman and Xi teaches temozolomide or temozolomide and cisplatin as administered as a chemotherapy ([0169]).
Regarding claims 6-7, 9 and 10, Newman teaches the chemotherapeutic as administered as a capsule ([0010]).
Regarding claims 6-8, Newman teaches administering the chemotherapeutic via injection in an aqueous vehicle ([0096]).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
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/LAUREN WELLS/Examiner, Art Unit 1622