DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-20 are pending.
Status of Priority
The present application is a 35 U.S.C. § 371 national stage patent application of International patent application PCT/US2022/011568, filed on January 07, 2022. This application also claims the benefits of U.S. Provisional Application No. 63/134,991, filed on January 08, 2021.
Information Disclosure Statement
The instant application is accompanied with no IDS. Examiner would like to remind Applicant that “[e]ach individual associated with the filing and prosecution of a patent application has a duty of candor and good faith in dealing with the Office, which includes a duty to disclose to the Office all information known to that individual to be material to patentability as defined in this section. The duty to disclose information exists with respect to each pending claim until the claim is cancelled or withdrawn from consideration, or the application becomes abandoned. Information material to the patentability of a claim that is cancelled or withdrawn from consideration need not be submitted if the information is not material to the patentability of any claim remaining under consideration in the application. There is no duty to submit information which is not material to the patentability of any existing claim. The duty to disclose all information known to be material to patentability is deemed to be satisfied if all information known to be material to patentability of any claim issued in a patent was cited by the Office or submitted to the Office in the manner prescribed by §§ 1.97(b) -(d) and 1.98. However, no patent will be granted on an application in connection with which fraud on the Office was practiced or attempted or the duty of disclosure was violated through bad faith or intentional misconduct.” See 37 C.F.R. 1.56 for more details.
Specification - Abstract
The abstract of the disclosure is objected to because it is not in compliance with 37 C.F.R. 1.72 (b). Specifically, the sheet presenting the abstract includes other parts of the application or other material. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Specification - Disclosure
The specification is objected to because of the following informalities:
On pg. 11, para. 0034, 1st line, “FIGs. 15A-15F” should read “FIGs. 15A-15E”;
Appropriate correction is required.
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 3 and 6 are objected to because of the following informalities:
Claim 3 should read: “… a 1,3,4-thiadiazole derivative, Compound 2, having a structure;”
Claim 6 should read: “The method of claim 5, wherein the statin comprises a lipophilic statin.” Appropriate correction is required.
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 1-20 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 following:
a method of treating a lung cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of an ABL inhibitor and a mevalonate pathway inhibitor
wherein the ABL inhibitor is ABL001 and the mevalonate pathway inhibitor is simvastatin
wherein the ABL is administered prior to, concurrently with, or after the mevalonate pathway inhibitor
wherein the lung cancer is a metastatic cancer comprising metastases in the brain of the subject
does not reasonably provide enablement for the remaining scope of the claimed genus beyond the enabled scope discussed above.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In evaluating the enablement question, several factors are to be considered. According to In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), these factors include:
1) The nature of the invention,
2) the state of the prior art,
3) the predictability or lack thereof in the art,
4) the amount of direction or guidance present,
5) the presence or absence of working examples,
6) the breadth of the claims, and
7) the quantity of experimentation needed, and
8) the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention
The nature of the invention claims a method of treating cancer in a subject by co-administering an ABL inhibitor and a mevalonate pathway inhibitor.
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State of the prior art
Prior art reference cited:
Oh et al. (Oh) (Oh, B. et al. Synergistic killing effect of imatinib and simvastatin on imatinib-resistant chronic myelogenous leukemia cells. Anti-cancer drugs 2013, 24, 20-31.)
Oh discloses that when mice were injected subcutaneously with K562 cells (a chronic myelogenous leukemia cell line; see abstract), the tumor-bearing mice can be treated with a combination of simvastatin and imatinib to result in “a greater than 50% decrease in tumor volume… indicating that cotreatment combination treatment effectively induced cell death [in vivo] compared with imatinib alone” (pg. 25, right col., “Simvastatin enhanced imatinib-induced growth arrest in an in-vivo mouse model” section, last paragraph). This result is summarized in the plot (Oh, Figure 2b) below:
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Oh, Figure 2b caption: “Simvastatin reduces the growth of K562-transplanted tumors. K562 cells were inoculated subcutaneously into nude mice as described. Ten days after inoculation, the mice were randomly assigned to five treatment groups (n =5)… (b) Tumors were measured using electronic calipers, and volumes were calculated using the formula tumor size (mm3) = (d2×D)/2, where d and D are the shortest and the longest diameters of the tumor, respectively. Results are expressed as mean±SD of the mean of the measurements from all five animals/group during the treatment. Significant difference versus the control group were analyzed by analysis of variance (*P<0.05).”
Instant claim 3 recites that imatinib is an ABL inhibitor. Instant claim 7 recites that simvastatin is a mevalonate pathway inhibitor. It is also noted here that simvastatin is also considered a prenylation inhibitor (See title and abstract of the following reference: Ostrowski, S. M. et al. Simvastatin inhibits protein isoprenylation in the brain. Neuroscience 2016, 329, 264-274.)
Therefore, the teachings of Oh anticipates instant claims 1, 3-8, and 18 because Oh teaches that the combination of imatinib (an ABL inhibitor) and simvastatin (a mevalonate pathway inhibitor) can treat a cancer (chronic myelogenous leukemia) in a subject (mice).
The level of the skill in the art
The level of ordinary skill in the art is relatively high. A person of ordinary skill would typically have formal training in oncology and/or medicinal chemistry and would be familiar with standard methods for evaluating therapeutic efficacy of individual compounds and/or a combination of compounds.
The amount of direction or guidance present and quantity of experimentation necessary
The prior art (i.e., Oh) does not disclose a method of treating any type of cancer in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of at least one of any ABL inhibitor and at least one of any mevalonate pathway inhibitor such that the cancer, of any type, is treated in the subject. In the absence of clear guidance, a person of ordinary skill in the art would require undue experimentation to determine which combination of ABL inhibitor + mevalonate pathway inhibitor can treat a cancer of any type.
Accordingly, the instant specification does not fully enable claims 1-20.
The presence or absence of working examples
In the instant specification, the term “treatment” refers to the “clinical intervention made in response to a disease, disorder or physiological condition (e.g., a cancer) manifested by a patient or to which a patient may be susceptible. The aim of treatment includes the alleviation or prevention of symptoms, slowing or stopping the progression or worsening of a disease, disorder, or condition and/or the remission of the disease, disorder or condition” (pg. 17, para. 0056). In the instant specification, the term “subject” and “patient” are used interchangeably and refer to both human and nonhuman animals, wherein the term “nonhuman animals” of the disclosure includes all vertebrates, e.g., mammals and non-mammals, such as nonhuman primates, sheep, dog, cat, horse, cow, chickens, amphibians, reptiles, and the like (pg. 17, para. 0057).
Instant claim 1 recites a method of treating a cancer in a subject by administering to the subject a therapeutically effective amount of at least one ABL inhibitor and at least one mevalonate pathway inhibitor. Based on the definition of “treatment” and “subject” as discussed above, the instant specification, therefore, must show working examples of a cancer being treated (e.g., a cancerous tumor decreasing in volume) in vivo.
Example 1 of the instant specification (pg. 31-39) is a “Materials and Methods” section and, therefore, does not provide working examples of a cancer being treated in a subject.
Examples 2-6 of the instant specification (pg. 39-47) disclose in vitro studies and, therefore, the findings from the in vitro studies cannot enable any of the instant claims since the claims are directed towards a method of treating cancer in a subject.
Example 8 of the instant specification discloses that ABL kinase inhibition impairs outgrowth of HER2+ breast cancer brain metastatic cells and improve overall survival of tumor-bearing mice. However, example 8 does not disclose a combination therapy of an ABL inhibitor and a mevalonate pathway inhibitor in treating breast cancer in tumor-bearing mice. Therefore, the findings from example 8 cannot enable any of the instant claims. This is because the claims are directed towards a method of treating cancer in a subject, the method comprising administering to the subject at least one ABL inhibitor AND at least one mevalonate pathway inhibitor (not at least one ABL inhibitor OR at least one mevalonate pathway inhibitor).
Example 7 (pg. 47-49) of the instant specification is the only example that investigates the combination therapy of an ABL inhibitor (specifically, ABL001) and a mevalonate pathway inhibitor (specifically, simvastatin) in impairing tumor growth and increasing survival in mouse models of lung cancer brain metastasis and gefitinib resistance. Example 7 does not disclose a combination therapy of other ABL inhibitors being administered with other mevalonate pathway inhibitors. The example also does not state that the subject was treated with at least one of an anti-cancer agent or radiotherapy nor does it state that the combination therapy can treat any cancer which includes skin cancer and breast cancer.
Therefore, the specification is only enabling for:
a method of treating a lung cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of an ABL inhibitor and a mevalonate pathway inhibitor
wherein the ABL inhibitor is ABL001 and the mevalonate pathway inhibitor is simvastatin
wherein the ABL is administered prior to, concurrently with, or after the mevalonate pathway inhibitor
wherein the lung cancer is a metastatic cancer comprising metastases in the brain of the subject
According to MPEP § 2163:
“Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’ See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014).
Even though the instant claim set recites different ABL inhibitors (claim 3) and mevalonate pathway inhibitors (claims 7 and 9), according to MPEP § 2163, disclosing a single working example of a combination therapy of an ABL inhibitor + a mevalonate pathway inhibitor in treating one cancer type in a subject does not adequately provide written description of a genus which embraces a method of treating any cancer by administering variant species of ABL and mevalonate pathway inhibitors to a subject. Thus, the specification is not adequately reflecting the claimed genus.
The breadth of the claims
The claims are broad insofar as the instant claims recite a method of treating any type of cancer in a subject by administering any ABL inhibitor in combination with any mevalonate pathway inhibitor to the subject in need thereof.
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 3 and 6 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 3 recites the broad recitation “1,3,4-thiadiazole derivatives,” and the claim also recites “Compound 2 having the structure
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which is the narrower statement of the range/limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 6 recites the limitation "wherein the statin comprises a lipophilic statin.” There is insufficient antecedent basis for this limitation in the claim because claim 4, in which claim 6 is dependent on, does not introduce the term, “statin.”
Note on 35 USC § 102 and § 103 Rejections
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3-8, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Oh et al. (Oh) (Oh, B. et al. Synergistic killing effect of imatinib and simvastatin on imatinib-resistant chronic myelogenous leukemia cells. Anti-cancer drugs 2013, 24, 20-31.)
Oh discloses that when mice were injected subcutaneously with K562 cells (a chronic myelogenous leukemia cell line; see abstract), the tumor-bearing mice can be treated with a combination of simvastatin and imatinib to result in “a greater than 50% decrease in tumor volume… indicating that cotreatment combination treatment effectively induced cell death [in vivo] compared with imatinib alone” (pg. 25, right col., “Simvastatin enhanced imatinib-induced growth arrest in an in-vivo mouse model” section, last paragraph). This result is summarized in the plot (Oh, Figure 2b) below:
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Oh, Figure 2b caption: “Simvastatin reduces the growth of K562-transplanted tumors. K562 cells were inoculated subcutaneously into nude mice as described. Ten days after inoculation, the mice were randomly assigned to five treatment groups (n =5)… (b) Tumors were measured using electronic calipers, and volumes were calculated using the formula tumor size (mm3) = (d2×D)/2, where d and D are the shortest and the longest diameters of the tumor, respectively. Results are expressed as mean±SD of the mean of the measurements from all five animals/group during the treatment. Significant difference versus the control group were analyzed by analysis of variance (*P<0.05).”
Instant claim 3 recites that imatinib is an ABL inhibitor. Instant claim 7 recites that simvastatin is a mevalonate pathway inhibitor. It is also noted here that simvastatin is also considered a prenylation inhibitor (See title and abstract of the following reference: Ostrowski, S. M. et al. Simvastatin inhibits protein isoprenylation in the brain. Neuroscience 2016, 329, 264-274.)
Therefore, the teachings of Oh anticipates instant claims 1, 3-8, and 18 because Oh teaches that the combination of imatinib (an ABL inhibitor) and simvastatin (a mevalonate pathway inhibitor) can treat a cancer (chronic myelogenous leukemia) in a subject (mice).
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 1-8, 10-12, and 15-20 are rejected under 35 U.S.C. 103 as being unpatentable over:
Oh et al. (Oh) (Oh, B. et al. Synergistic killing effect of imatinib and simvastatin on imatinib-resistant chronic myelogenous leukemia cells. Anti-cancer drugs 2013, 24, 20-31.),
Gu et al. (Gu) (Gu, J. J. et al. Inactivation of ABL kinases suppresses non–small cell lung cancer metastasis. JCI Insight 2016, 1, e89647; pg. 1-16), and
Pendergast et al. (Pendergast) (US 2020/0215066 A1; published July 9, 2020).
The teachings of Oh as they apply to claims 1, 3-8, and 18 are as discussed in “Claim Rejections - 35 USC § 102” and incorporated herein.
Oh does not teach that an ABL inhibitor can treat metastatic tumors in mice. Gu is relied upon for this disclosure.
Gu discloses “data showing profound suppression of NSCLC [i.e., non-small cell lung carcinoma] metastasis [to brain and bone] by the ABL allosteric inhibitors in mice suggest that these compounds might be effective to treat metastatic NSCLC with a hyperactive ABL signature” (pg. 11, last sentence and abstract). Gu further discloses that “GNF5 treatment of mice with established metastatic tumors following detection by BLI showed that the ABL allosteric inhibitor also effectively inhibited the growth of well-established PC9M metastatic lesions (Figure 3, E and F). Together these data demonstrate that allosteric inhibition of ABL kinases is an effective therapeutic strategy to suppress multiple-organ metastasis by lung cancer cells” (pg. 4, 1st paragraph below the Figure 3 caption). It is noted here that Gu does not teach the administration of an ABL allosteric inhibitor in combination with a mevalonate pathway inhibitor to a subject in need thereof.
Therefore, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the claimed invention to combine the teachings of Oh and Gu to develop a method of treating NSCLC with brain metastasis by administering GNF5 (an ABL allosteric inhibitor) in combination with simvastatin (a mevalonate-pathway inhibitor) (reads on instant claims 1-8, 15-18, and 20). In view of Oh, which reports synergy between imatinib and simvastatin in treating a cancer, a person of ordinary skill in the art would have been motivated to combine the teachings of Oh and Gu to evaluate whether GNF5 (an ABL inhibitor) in combination with simvastatin would, likewise, yield a synergistic antitumor activity against NSCLC. This motivation is reinforced by Gu which shows that GNF5 alone exhibits antitumor activity in NSCLC metastatic tumors in mice. The teachings from both Oh and Gu provide a reasonable expectation of success that the combination of an ABL inhibitor, like GNF5, and a mevalonate pathway inhibitor, like simvastatin, would improve outcomes relative to monotherapy in treating NSCLC metastatic tumors.
Gu does not disclose multiple ABL inhibitors that a POSITA can try to use in combination with a mevalonate pathway inhibitor. Gu also does not disclose the administration order of an ABL inhibitor and a an additional therapeutic agent. Pendergast is relied upon for this disclosure.
As stated above, a POSITA would have found it obvious to develop a method of treating NSCLC with brain metastasis by administering GNF5 (an ABL allosteric inhibitor) in combination with simvastatin (a mevalonate-pathway inhibitor). It would have also been obvious-to-try for a POSITA to administer simvastatin with another ABL inhibitor such as those listed in claim 9 and 20 of Pendergast (which includes ABL001) (reads on instant claims 3 and 19). Note, the ABL inhibitors listed in Pendergast are the same ABL inhibitors recited in instant claim 3.
According to MPEP §2145:
“An ‘obvious to try’ rationale may support a conclusion that a claim would have been obvious where one skilled in the art is choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. ‘[A] person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.’ KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421, 82 USPQ2d 1385, 1397 (2007).”
A person of ordinary skill in the art would have been motivated to evaluate the therapeutic combinations of simvastatin with other ABL inhibitors to identify an optimal combination for treating NSCLC metastatic tumors.
Pendergast further discloses a composition comprising an ABL inhibitor and a pharmaceutically acceptable carrier or excipient (claim 20) and states that “[t]he co-administration may comprise administering the composition(s) of the present disclosure before, after, or at the same time as the additional therapeutic agent” (pg. 14, para. 0163, 2nd sentence). Therefore, one of ordinary skill in the art would have also found it obvious to try and administer an ABL inhibitor before, after, or at the same time as a mevalonate pathway inhibitor (i.e., an additional therapeutic agent) (reads on instant claims 10-12). A POSITA would have been motivated to evaluate dosing sequence to determine whether order of administration affects combination efficacy.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-12, and 15-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-2 of U.S. Patent No. US11883401B2 (‘401B2) in view of
Oh et al. (Oh) (Oh, B. et al. Synergistic killing effect of imatinib and simvastatin on imatinib-resistant chronic myelogenous leukemia cells. Anti-cancer drugs 2013, 24, 20-31.) and
Sun et al. (Sun) (Sun, J. et al. Ras CAAX Peptidomimetic FTI 276 Selectively Blocks Tumor Growth in Nude Mice of a Human Lung Carcinoma with K-Ras Mutation and p53 Deletion1. Cancer Research 1995, 4243-4247.),
Although the claims at issue are not identical, they are not patentably distinct from each other because there is overlap between the instant claim set and the claim set from the granted patent.
Claims 1-9, and 15-20 of the instant application are directed towards a method of treating a cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of at least one ABL inhibitor and at least one mevalonate pathway inhibitor such that the cancer is treated in the subject.
Claims 1-2 of application ‘401B2 is directed towards a method of treating a non-small cell lung cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an ABL kinase inhibitor in combination with a chemotherapeutic agent (‘401B2, claim 1) wherein the non-small cell lung cancer is a lung adenocarcinoma (‘401B2, claim 2). Claims 1-2 of application ‘401B2 do not specify the stage of cancer and, therefore, is broad enough that it encompasses non-small cell lung metastatic cancer comprising metastases in the brain of a subject (reads on instant claims 2 and 20).
The National Cancer Institute defines “chemotherapeutic agent” as a drug used to treat cancer.
According to the instant specification, the aim of a disease “treatment” includes the alleviation or prevention of symptoms, slowing or stopping the progression or worsening of a disease, disorder, or condition and/or the remission of the disease, disorder or condition” (pg. 17, para. 0056). Since simvastatin (a mevalonate pathway inhibitor as disclosed in instant claim 7) alone can reduce the growth of K562-transplanted tumors in vivo (wherein K562 is a chronic myelogenous leukemia cell line; see abstract of Oh) (Oh, Figure 2 caption, 1st sentence), simvastatin can be considered a chemotherapeutic agent. Therefore, claims 1-2 of application ‘401B2 are not patentably distinct from instant claims 1, 3-7, and 15-19.
Similarly, since FTI-276, a farnesyltransferase inhibitor, exhibits antitumor activity against human lung carcinoma in vivo (Sun, Fig. 2 and Fig. 2 caption), a prenylation inhibitor like FTI-276 can be considered a chemotherapeutic agent. Note: FTI-277 is the carboxyl methyl ester form of FTI-276 (i.e., the pro-drug form of FTI-276 that is more cell permeable than FTI-276; pg. 4244, left col., “Results and Discussion” section, 1st paragraph, 3rd and 5th sentence). “The similar antitumor efficacies of FTI-276 and FTI-277 suggest that FTI-277 is rapidly converted to FTI-276 before it reaches its target, tumor FTase (pg. 4245, left col., 2nd paragraph). Therefore, one of ordinary skill in the art would have found it obvious to administer FTI-277 as a chemotherapeutic agent and claims 1-2 of application ‘401B2 are also not patentably distinct from instant claims 8-9.
According to the specification of application ‘401B2, the “co-administration may comprise administering the composition(s) of the present disclosure before, after, or at the same time as the additional therapeutic agent” (col. 26, lines 16-18). Therefore, claims 1-2 of application ‘401B2 are directed towards a method of treating a non-small cell lung cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an ABL kinase inhibitor in combination with a chemotherapeutic agent (‘401B2, claim 1) wherein the non-small cell lung cancer is a lung adenocarcinoma (‘401B2, claim 2) and wherein the ABL inhibitor can be administered before, after, or at the same time as the chemotherapeutic agent. Therefore, claims 1-2 of application ‘401B2 are also not patentably distinct from instant claims 10-12.
Conclusion
No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY H. MURRAY can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624