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
Status of 17/781,699
Claims 1, 20, 41-43, 48-49, 51-55, 60-61, 63-67, and 73 are currently pending.
Priority
Instant application 17/781,699, filed 6/1/2022, claims priority as follows:
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The application PCT/CN2019/122402 contains support for the instant claims, and thus, claims 1, 20, 41-43, 48-49, 51-55, 60-61, 63-67, and 73 are granted the effective filing date of 12/2/2019. The Examiner notes the foreign application China 2020/1129594.7 with the date 11/18/2020 was not evaluated as it is not translated into English.
Information Disclosure Statement
All references from the IDS submitted on 6/1/2022 have been considered unless marked with a strikethrough.
Additionally, the Examiner notes a list of references in the specification on page 67, and each of these documents are therefore understood to be pertinent and material to patentability. However, these documents were not placed on record in the form of an IDS. Applicant is advised that the listing of references in the specification is not a proper format information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, “the list may not be incorporated into the specification but must be submitted in a separate paper.” Therefore, unless the references have been cited by the Examiner on form PTO-892, they have not been considered.
Objection to the Abstract
The abstract is objected to because it solely contains content relevant to instant claim 1. The method claims, including the claims examiner herein, are not reflected in the abstract. 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).
Objection to Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because Figures 1-14 are not able to be interpreted as they are in black and white, and pixelated. It is unclear what lines correspond to the labels in the drawings. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Election/Restriction
Applicant’s election of Group II, claims 20, 41-43, 48-49, and 51, drawn to a method of treating a disease with a combination of the IAP inhibitor recited in claim 20 and a PARP or MEK inhibitor without traverse, in the reply filed 7/10/2025 is acknowledged. Applicant’s election of trametinib as the MEK inhibitor and ovarian cancer as the disease, without traverse and for search purposes only, in the reply filed 7/10/2025 is also acknowledged.
Examination will begin with the elected species. In accordance with MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non- elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be examined again. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during further examination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
The elected species was searched and prior art was identified. See the 103 rejection below. The full scope of the claims has not yet been searched in accordance with Markush search practice. Claims 20, 41-43, 48-49, and 51 read on the elected species. Claims 1, 52-55, 60-61, 63-67, and 73 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species and/or group, there being no allowable generic or linking claim.
Claim interpretation
Claim 20 recites the phrase, “effective amount”, in reference to the dosage amounts of the IAP inhibitor and the second inhibitor in the methods of treatment. The specification defines this term as the amount of the active ingredient(s) that is(are) sufficient to efficaciously deliver the active ingredient(s) for the treatment of the condition or disease or interest (page 12, para [0061]). Further, in the same paragraph, examples are given of about 0.1 mg to about 50 g per day, alternatively from 1 mg to about 5 grams per day; and in another alternative from 10 mg to 1 gram per day. Thus, this phrase in the claim is currently being interpreted as within the given ranges.
Claims 48-49 and 51 recite broad and narrow dosage range limitations, which according to MPEP § 2173.05(c), may render the claim indefinite when the boundaries of the claim are not discernible. However, since each range is distinctly separated by “or” logic, one of ordinary skill can identify boundary of the claim and a teaching inside any one of those ranges would meet the limitations of the claim. Currently, the broad and narrow dosage range limitations are being interpreted as alternative ranges and there is no question as to whether one is required or not since the logic is that meeting anyone of the alternatives would meet the claim limitation. Stated differently, though the instant claims recite broad and narrow dosage range limitations, the limitations do not meet the bar for a 35 U.S.C. 112(b) rejection because they are currently being interpreted as alternative ranges and any one of the alternatives would meet the claim limitation.
Claim Objections
Claim 20 is objected to because it recites the MEK inhibitors E-6201 and SL-327 twice. Appropriate correction is required.
Claim 41 is objected to because it recites the phrases, “and inflammatory disease” and “a hyperproliferative diseases”. The claim should be amended to fix these minor informalities to recite, “an inflammatory disease” and “a hyperproliferative disease”, respectively. 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 20, 41-43, 48-49, and 51 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 20 recites the limitations of LNP-3794, SHR-7390, ATR series -001, -006, -004, -005, CS-3006, CIP-13741, SC-1-151, SRX-2626, GSK-2091976A, AS-703988, CZ-775, RDEA-436, MEK-300, and AD-GL000l as MEK inhibitors. The structures of the compounds are not disclosed in the claims, specification, or in the prior art, and thus, the limitations are considered indefinite. Dependent claims 41-43, 48-49, and 51 do not resolve this issue by defining the structure of these compounds and are therefore also rejected. Appropriate correction is required.
Claims 48-49 and 51 recite the term, “about”, in reference to the dosage amounts of the IAP inhibitor and the second inhibitor. The term “about” in claims 48-49 and 51 is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, the scope of the dosage amounts of the IAP inhibitor and the second inhibitor is rendered indefinite by the term “about”. Appropriate correction is required. In the interest of compact prosecution, the term “about” is currently being interpreted to mean ±10% of the subsequent value modified by the term.
Claim Rejections - 35 USC § 112(a)
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 20, 48-49, and 51 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, "To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966." Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
In the instant case, the claims are drawn to a method of treating a disease, comprising administering to a subject in need thereof effective amounts of the IAP inhibitor and a second inhibitor, selected from a PARP inhibitor or a MEK inhibitor. Specifically, claim 20 is drawn to a method of treating any disease with the combination of the IAP inhibitor and a PARP or MEK inhibitor, regardless of the mechanism of action of the said disease. Stated differently, there is not known or disclosed structure/function relationship between the IAP inhibitor and PARP or MEK inhibitor combination and the ability to treat all diseases as claimed.
The full scope of diseases able to treated with the combination of the IAP inhibitor and the PARP or MEK inhibitor, where said diseases varying respective mechanisms of action, is not fully defined in the instant disclosure. Further, the specification asserts a list of diseases that are able to be treated by combination of the IAP inhibitor and the PARP or MEK inhibitor, and provides the sole example of the combination of the IAP inhibitor and the PARP or MEK inhibitor treating cancer. Thus, it is unclear where the line of possession of knowledge lies.
A review of the art identifies Jiangsu Ascentage Biomed Development Inc. (WO 2019/101047, herein after “Jiangsu”), which discloses bisdiazabicyclo compounds and their methods of treating disease or disorders associated with a hepatitis virus (abstract). Specific)ally, Jiangsu teaches compound 1 (page 18), which is identical to the IAP inhibitor recited in instant claim 20, to treat hepatitis B infections alone and in combination with other compounds (starting page 21, Examples 1-2 and 5-8). Apart from the hepatitis B virus, there are no other examples or indications of Jiangsu of treating other diseases. Thus, in light of the teachings of Jiangsu, it is unknown if the IAP inhibitor treats or elicits the desired biological effect in any disease as claimed, and one of ordinary skill in the art would not be readily able to predict the structural aspects necessary for the desired biological outcome.
Additional prior art identified is The Regents of the University of Michigan (WO 2014/031487, cited in the IDS of 6/1/2022, herein after “Michigan”) which teaches inhibitors of IAP proteins and compositions thereof, and their use in methods of treatment of diseases and conditions where inhibition of IAP proteins provides a benefit (abstract). Specifically, Michigan teaches the instantly claimed IAP inhibitor in claim 20 as compound 23, which is able to inhibit breast and ovarian cancer cell lines. There are no other teachings of Michigan that indicate the IAP inhibitor can treat other diseases, and thus, it is unknown if the IAP inhibitor treats or elicits the desired biological effect in any disease as claimed, and one of ordinary skill in the art would not be readily able to predict the structural aspects necessary for the desired biological outcome. Applicant has not demonstrated that they were in possession of the knowledge of which diseases the combination of the IAP inhibitor and PARP or MEK inhibitor is able to treat.
In addition to the lack of structure/function relationship established, there is additionally an insufficient representative number of examples. As described in MPEP § 2163, for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. The instant specification solely provides examples of the combination of the IAP inhibitor and the PARP or MEK inhibitor treating pancreatic cancer, indicating that the instant disclosure does not provide descriptive support for the genus of the claims. Applicant has not described the claimed genus of treating any disease with LSD in a manner that would indicate they were in possession of knowledge of the full scope of the genus, or even to describe what this genus is comprised of.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.") Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Dependent claims 48-49 and 51 do not resolve these issues, since these claims do not further limit or provide further definition of the diseases able to be treated. Accordingly, claims 48-49 and 51 are also rejected.
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 (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.
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 20, 41-43, 48-49, and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Li (Li, B. et. al. Journal of Experimental & Clinical Cancer Research, 2018, 37:53) as evidenced by AOBIOUS (https://aobious.com/aobious/enzyme-inhibitors/13476-apg-1387.html) in view of The Regents of the University of Michigan (WO 2014/031487, cited in the IDS of 6/1/2022, herein after “Michigan”) and in further view of Jing (Jing, Y. et. al. Oncotarget. 2016, 7, 2545-2554). This rejection applies to the elected species.
Determining the scope and contents of the prior art
The reference Li teaches methods of treating ovarian cancer cell lines SKOV3 and OVCAR3 (Page 4, Figure 1) and SKOV3 nude mice xenograft models with the compound APG-1387 at dosages of 1, 3, and 10 mg/kg (Figures 8a and 8b). Though not explicitly stated in Li, the compound APG-1387 is the same as the compound of claim 20, as evidenced by AOBIOUS.
The reference Michigan teaches methods of treating ovarian cancer cell line SKOV3 with the compound recited in instant method 20 as compound 23 (page 72):
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And further teaches that methods of treatment can be combined with one or more second therapeutic agents (page 32, para [0104]), such as an MEK-1 kinase inhibitor (page 41, para [0132). Additionally, Michigan teaches the administration of the first and second agents can be done simultaneously or sequentially to achieve the desired effect (page 31, para [0100]).
The reference Jing teaches methods of treatment of ovarian cancer with BET and MEK inhibitors (abstract), and specifically teaches the compound trametinib as suppressing ovarian tumor growth by itself and it in combination with additional pharmaceutical agents in xenograft models (Figures 5B and 5C). Additionally, Jing teaches that trametinib was dosed in a quantity of 1 mg/kg/day (Materials and Methods, in vivo study section).
Ascertaining the differences between the prior art and the claims at issue
Li and Michigan fail to teach the treatment of ovarian cancer with pharmaceutical combinations comprising trametinib, whereas Jing fails to teach the treatment of ovarian cancer with the compound recited in instant claim 20, also known as APG-1387.
Resolving the level of ordinary skill in the pertinent art
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of bifunctional compounds capable of degrading BTK via a ubiquitin proteolytic pathway. An artisan possess the technical knowledge necessary to make adjustments to the bifunctional compounds to enhance their effectiveness. Said artisan has also reviewed the problems in the art as regards to use of said bifunctional compounds capable of degrading BTK via a ubiquitin proteolytic pathway and understands the solutions that are widely known in the art.
Considering objective evidence present in the application indicating obviousness or nonobviousness
Applying KSR prong A, it would have been prima facie obvious to combine the methods of treating ovarian cancer with the IAP inhibitor with the methods of treating ovarian cancer with trametinib because they have the same purpose and are both known to be successful in treating the same disease. One of ordinary skill in the art would be motivated before the effective filing date of the claimed invention to combine the methods to maximize the treatment of ovarian cancer, and would reasonably predict the combination would be successful in view of the teachings of Li, AOBIOUS, Michigan, and Jing.
With respect to claims 48-49 and 51, it would have been prima facie obvious to one having ordinary skill in the art to arrive at the dosages of the IAP inhibitor and trametinib, the second inhibitor, recited in the instant claims because it is considered well within the capabilities of one of ordinary skill in the art to optimize the administration amounts of individual pharmaceuticals to provide optimal ovarian cancer treatments. The concentration of each individual ingredient in the pharmaceutical combination is a result effective parameter that will affect the physical properties of the final composition. The amount of the IAP inhibitor in a composition is clearly a result effective parameter that a person of ordinary skill would routinely optimize, as is trametinib, the second inhibitor. Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Moreover, the dosages of the IAP inhibitor and trametinib, disclosed by Li, Michigan, and Jing above, provide a range of workable conditions and it would have been customary for an artisan of ordinary skill to determine the optimal dosages to best achieve the desired result. Furthermore, absent any evidence demonstrating a patentable difference between the composition and the criticality of the claimed amounts, the determination of the optimum workable range(s) given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. See MPEP § 2144.05 [R-2](II) (A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) “[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Conclusion
Claims 20, 41-43, 48-49, and 51 are rejected. Claims 1, 52-55, 60-61, 63-67, and 73 are withdrawn.
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/K.N.H./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621