DETAILED ACTION
Claims 2-19 are currently pending in the instant application.
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
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Information Disclosure Statement
Applicant's Information Disclosure Statements filed on 12/02/2024 and 04/16/2025 have been considered. Please refer to Applicant's copies of the 1449 submitted herewith.
Claim Rejections - 35 USC § 112
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.
Claim 17 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 17 recites “additional disease with pronounced neurodegeneration such as …” as well as “diseases and disorders associated with acquired brain injury such as…” in the claim. Regarding claim 17, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Further, it is unclear how pronounced neurodegeneration can be determined, which renders the scope of the claim unclear. Additionally, it is unclear what the scope of diseases and disorders “associated with acquired brain injury” could include. For example, if a fall occurs due to a brain injury, would this be considered a disease associated with such an injury? Thus, the metes and bounds of limitation and claim are unclear.
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 2-19 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 treatment of disorders characterized by abnormal expression and/or activity of DYRK1A selected from the group consisting of a neurological disorder, diabetes and cancer, does not reasonably provide enablement for treating a neurological disorder, diabetes and cancer. 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 the invention commensurate in scope with these claims.
"Each claim must be separately analyzed and given its broadest reasonable interpretation in light of and consistent with the written description." MPEP 2163(II)(1), citing In re Morris,127 F.3d 1048, 1053-1054; 44 USPQ2d 1023, 1027 (Fed. Cir. 1997). Accordingly the scope of diseases claimed to be treated would be all types of cancerous tumors, ranging from breast cancer, prostate cancer, lung cancer, etc. Further this would include many neurological disorders. Given the scope of the many types of cancerous tumors included within the claims, their varied etiologies, and the diversity of their patient populations, the disclosure in the Specification is insufficient to permit a person skilled in the art to employ a compound for the purpose of treating the scope of the disorders as claimed.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988).
In In re Wands. 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
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,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
The nature of the invention
In the instant case, the nature of the invention is for the treating a neurological disorder, diabetes and cancer comprising administering a compound of formula (I).
The state of the prior art and the predictability or lack thereof in the art
The state of the prior art is that the pharmacological art involves screening invitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat a neurological disorder, diabetes and cancer). There is no absolute predictability even in view of the seemingly high level of skill in the art.
MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” In Ex parte Stevens, 16 USPQ2d 1379 a claim to “A method for therapeutic or prophylactic treatment of cancer in mammalian hosts” was refused because there was “no actual evidence of the effectiveness of the claimed composition and process in achieving that utility.”
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427F.2d833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. With specific reference to cancer, Ex parte Kranz, 19 USPQ2d 1216, 1219 notes the “general unpredictability of the field [of] …anti-cancer treatment.” In re Application of Hozumi et al., 226 USPQ 353 notes the “fact that the art of cancer chemotherapy is highly unpredictable”. In the instant case, the specification does not provide guidance as to how one skilled in the art would accomplish the objective of treating all cancers
The state of the prior art is that cancer therapy remains highly unpredictable. Cancer is not a single disease, or cluster of closely related disorders. There are hundreds of cancers, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level, something seen especially in, for example, the cancers of the breast, brain and salivary glands. They can occur in pretty much every part of the body. The various types of cancers have different causative agents, involve different cellular mechanisms, and consequently, differ in treatment protocol. It is known that the challenge of cancer treatment has been to target specific therapies to pathogenetically distinct tumor types and that cancer classification has been based primarily on morphological appearance of the tumor. Tumors with similar histopathological appearance can follow significantly different clinical courses and show different responses to therapy (Golub et al, page 531).
According to information from the National Cancer Institute, targeted cancer therapies, is a type of cancer treatment that targets proteins that control how cancer cells grow, divide, and spread (see http://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet, accessed 04/20/2026). Most targeted therapies are either small-molecule drugs or monoclonal antibodies. They treat cancer by interfering with specific proteins that help tumors grow and spread throughout the body. Drugs for some targets are hard to develop due to target’s structure, target’s function in the cell, or both. Targeted therapies are specific to treat specific cancers. Due to the unpredictable nature of cancer and the fact that over 3,000 different cancers exist, the various types of cancers have different causative agents, involve different cellular mechanisms, and differ in treatment protocol, thus no single compound exists presently that is known to treat all cancers as a blanket therapeutic.
Regarding neurological disorders, Rizk et al teach that neurological disorder is a term used to describe a disease of central nervous system, as a result of physical injury to the brain, spinal cord, or nervous. Other causes may be due to changes in certain biochemical aspects or even the cause may be unknown by the effects on CNS are observed (see p. 32). There are numerous neurological diseases with different causes and symptoms. Rizk et al teach that finding clinically relevant biomarkers of human neurological disorder attracts a lot of interest. Moreover, most neurological disorders are recognized too late, leading to late therapy and poor prognosis. Additionally, most current clinical chemistry tests are neither sensitive nor specific. Neurodegenerative disorders are of great social and economic burden and cause significant load on both patients and healthcare costs. Treatment options for patients are still limited and provide modest symptomatic relief (see p. 35)
Uyyala teaches that neurological disorders are complex and heterogeneous, making them difficult to fully understand (see p. 6). There is a gap between discoveries made in basic research and clinical applications. Advances in scientific research continue to uncover genetic, molecular and cellular mechanisms underlying these conditions, enabling identification of new therapeutic targets (see p. 20). Drug delivery remains a challenge since effective treatment of neurological disorders depends on delivery of therapeutic agents to the CNS. The blood-brain barrier poses a major obstacle as it is a highly selective barrier that protects the brain by regulating the exchange of substances between the bloodstream and neural tissue, which significantly limits drug accessibility (see p. 14). Additionally reliable biomarkers are essential for tracking disease progression and treatment effectiveness. However, developing acute and consistent biomarkers remains significant challenge (see p. 16).
The amount of direction and the presence of working examples
The specification does not provide examples of treatment of diseases. The compounds are screened in assays for DYRK1A kinase activity (see Example 13, p. 292-294) and for phosphorylation activity (see Example 14, p. 295-296). The Specification states that abnormal expression and/or activity of kinases such as DYRK1A is seen in human nervous system diseases, neurodegenerative diseases, cancers, etc. (see p. 1-2).
The breadth of the claims
The instant breadth of the rejected claims is broader than the disclosure, specifically, the instant claims include treating a neurological disorder, diabetes and cancer. However the specification only provides evidence that the compounds have an inhibitory effect on DYRK1A kinase.
The quantity or experimentation needed and the level of skill in the art
It would require undue experimentation of one of ordinary skill in the art to ascertain the effectiveness of the compound in treating a neurological disorder, diabetes and cancer. Factors such as "sufficient working examples", "the level of skill in the art" and "predictability", etc. have been demonstrated to be sufficiently lacking in the instant case for the method of use claims. Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, it is apparent that undue experimentation is necessary because of variability in prediction of outcome that is not addressed by the present application disclosure, examples, teaching and guidance presented. Absent factual data to the contrary, the amount and level of experimentation needed is undue.
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.
Claims 2-6, 9, 13, 16 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over MOEBIUS (see WIPO Pub. No. 2019/074962, filed 10/09/2018 and published 04/18/2019, cited in IDS filed 12/02/2024).
MOEBIUS teaches compounds of formula
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and compositions comprising said compounds as having inhibition of a TAM kinase (see paragraphs [0002]-[0005] , p. 2-3). MOEBIUS further exemplifies compounds such as
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,
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,
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and
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(see Fig. 1, p. 10, 43 and 45 of 128). The compounds are used to treat a patient having cancer, which includes cancer such as ovarian cancer (see claim 30, p. 150). Further, the subject is said to be a human patient, see paragraph [0014], p. 5. Compound 193 corresponds to compound 10 (see p. 30 of the Specification). These compounds compound of the instant invention wherein R1 (as described in instant claim 2) is
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R2 is(C1-5 alkylene)pOR4 wherein each –(C1-5 alkylene) is optionally substituted with 1-3 unsubstituted –(C1-3 alkyl), R4 is unsubstituted –(C1-9 alkyl) and p is 1. MOEBIUS exemplifies L2-R2 (as defined in MOEBIUS) as bond-carbocyclyl rather than H as found in the instant claims. However, MOEBIUS explicitly teaches H as a possibility in a list of possibilities for R2:
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(see p. 21) and discloses L2 to be a bond (see paragraph 0082], p. 31) and in the compound of formula II
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(see paragraph [0095], p. 33) where R1, R2 and R3 are as defined for compounds of formula I.
When a person of ordinary skill is faced with “a finite number of identified, predictable solutions” to a problem and pursues “the known options within his or her technical grasp,” the resulting discovery “is likely the product not of innovation but of ordinary skill and common sense.” KSR, 127 S. Ct. at 1742. So too, “[g]ranting patent protection to advances that would occur in the ordinary course without real innovation retards progress.” Id. at 1741.
The Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
The motivation to substitute a hydrogen for a cycloalkyl would derive from (B) from KSR as well as the teaching of MOEBIUS that in the generic structure that R2 may be selected from:
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. It is common for one skilled in the art to synthesize structurally related compounds in hopes of obtaining greater activity on the desired target – a process known as structure-activity relationship (SAR) in the chemical arts. In the instant case, substitution of a hydrogen for a cycloalkyl (as exemplified in the compounds of MOEBIUS) would have been desirable in order to find further compounds that limit inhibit a TAM kinase to treat cancer. The explicit teaching of MOEBIUS together with the enabled examples would have motivated one skilled in the art to modify the known compounds with the expectation that that would have similar utility.
Conclusion
None of the claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN CHENG whose telephone number is (703)756-4699. The examiner can normally be reached M-F, 9AM-6PM PST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan can be reached at 571-270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KAREN CHENG/Primary Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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