DETAILED ACTION
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 .
Application Status
Claims 1, 3, 4, 7, 9, 13, 16, 18, 20, 22, 24, 30-32, 35, 37, 39, 40 and 43-53 are present in the application, under examination, and the subject of this office action.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on June 4, 2024, January 13, 2025, October 8, 2025, February 24, 2026, and June 4, 2026, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner, please refer to the signed copies of Applicant’s PTO-1449 forms, attached herewith.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class. For processes, the type of reaction, reagents and process conditions should be stated, generally illustrated by a single example unless variations are necessary.
The abstract of the disclosure is objected to because the chemical compounds have not been identified.
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).
Claim Objections
Claim 3 is objected to regarding the limitation “wherein L is a -C(=O)-”. It is recommended that the term “a” be deleted so that the limitation reads “wherein L is -C(=O)-”.
Claim Rejections - 35 USC § 112(a)
7. 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.
8. Claims 1, 3, 4, 7, 9, 13, 16, 18, 20, 22, 24, 30-32, 35, 37, and 40 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 contains 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.
In particular, support cannot be found for the full scope of compounds of Formula (I), as instantly claimed.
9. The MPEP §2163 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 by him. In the case of chemical entities, Applicant's attention is further directed to Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089, 118 S. Ct. 1548 (1998), which notes that an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, “not a mere wish or plan for obtaining the claimed chemical invention.” While the court recognizes that, “[i]n claims involving chemical materials, generic formulae usually indicate with specificity what the generic claims encompass” (Id.), it is also recognized that for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim and/or the genus must be sufficiently detailed to show that applicant was in possession of the claimed invention as a whole (see Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555 (Fed. Cir. 1991)). If a genus has substantial variance, the disclosure must present a sufficient number of representative species that encompass the genus in order to adequately describe the genus (i.e., the disclosure must describe a sufficient variety of species to reflect the variation within that genus). See MPEP § 2163. Otherwise, as stated by the court in Ariad Pharmaceuticals, Inc., v. Eli Lilly and Company (Fed. Cir. 2010), “a generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the applicant has invented species sufficient to support a claim to a genus.
10. The factors considered in the Written Description requirement are:
(1) level of skill and knowledge in the art,
(2) partial structure,
(3) physical and/or chemical properties,
(4) functional characteristics alone or coupled with a known or disclosed
correlation between structure and function, and
(5) the method of making the claimed invention.
11. Level of skill and knowledge in the art: The level of skill to practice the art of the instantly claimed invention is high and requires a variety of skills usually found in institutions and companies that employ highly trained and skilled scientists and/or physicians to carry out these tasks.
12. Partial structure; Physical and/or chemical properties; and Functional characteristics: The claims are drawn to a method of treating mild cognitive impairment in a subject in need thereof, comprising administering an effective amount of a compound of formula (I)
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or a pharmaceutically acceptable salt thereof. In the instant case, it is evident that the genus of compounds embraced by formula (I) has substantial variance, i.e., the moiety R3 alone can be C2-C6 alkyl or any 5- to 10-membered heteroarylalkyl, and R4 can be any C6-C10 aryl or 5- to 10-membered heterocyclyl or 5- to 10- membered heteroaryl. Indeed, the genus is virtually without limit, embracing hundreds of millions of potential compounds bearing little structural resemblance to one another what-so-ever. Yet, the instant Specification discloses only approximately 54 structurally related compound species within formula (I) in the synthesis examples of Compounds 1-54 and some of the intermediates involved in said syntheses at pages 60-99.
13. While the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number of species to adequately describe a broad generic. For example, in In re Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d 1008 (Fed. Cir. 1989). In the instant case, it is similarly determined that the disclosure of 14 structurally related compounds does not adequately describe a subgenus embracing hundreds of millions of additional compound species bearing no structural relationship with those 54 disclosed compounds. That is, the Specification does not disclose a sufficient variety of species to reflect the extreme variance in the genus.
14. The instant specification teaches that the instant genus of compounds of Formula (I) are hepatocyte growth factor (HGF) modulators, which are useful for treating HGF-modulated diseases including neurodegenerative diseases (paragraph [0004]). The Specification provides data demonstrating the potency of certain exemplary compounds towards HGF/MET in vitro in Example B1; demonstrates cell scattering behavior of MDCK cells following HGF treatment with certain exemplary compounds in Example B2; provides a solubility assay in Example B3; provides a permeability assay in Example B4; provides a cytotoxicity assay in Example B5; provides an in vitro stability assay in Example B6; demonstrates in vivo pharmacokinetics in Example B7; provides oral availability in Example B8; demonstrates non-specific protein binding in Example B9; demonstrates in vivo tissue distribution in Example B10 (see pages 99-113); and demonstrates the ability of just one compound (1a) to provide protection from neurotoxicity in vitro in Example B12. The only in vivo efficacy studies are provided in Example B11, wherein just two compounds (Compounds 2a and 6a) demonstrate the ability to reverse scopolamine-induced spatial memory deficits in rats (Table 12 and pages 113-115), and in Example B13, wherein just two compounds (Compounds 1a and 5a) demonstrate the ability to protect against scopolamine-induced cognitive impairment (pages 115-117). Thus, the instant Specification has not demonstrated support for all possible alternatives of the genus of compounds of Formula (I).
15. Despite the advanced training of those in the art, the pharmaceutical art is highly unpredictable. It is still not possible to predict the pharmacological activity or treatment efficacy of a compound based on the structure alone. Typically, in order to verify that a compound will be effective in a method or treating a disease, the compounds must be either tested directly in a patient or in a model that has been established as being predictive of efficacy. It is not predictable from the specification or from the prior art that the full scope of the genus of compounds of formula (I) modulates HGF in a culture or in the cells of a subject, for treating cognitive impairment.
16. The level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. Ariad, 598 F.3d at 1351, 94 USPQ2d at 1172; Capon v. Eshhar, 418 F.3d 1349, 1357-58, 76 USPQ2d 1078, 1083-84 (Fed. Cir. 2005).
Applicants have failed to provide guidance or data or evidence as to how the skilled artisan would be able to extrapolate from the disclosure to use the claimed invention. “A description of what a material does, rather than of what it is, usually does not suffice." Rochester, 358 F 3d at 923; Eli Lilly, 119 at 1568. Instead, the “disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described.” Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) 17. The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
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.").
18. Accordingly, it is deemed that the specification fails to provide adequate written description for the claimed invention and does not reasonably convey to one skilled in the relevant art that the inventors had possession of the entire scope of the claimed invention.
As such, claims 1, 3, 4, 7, 9, 13, 16, 18, 20, 22, 24, 30-32, 35, 37, and 40 are rejected.
Claim Rejections - 35 USC § 112(a)
19. 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.
20. Claims 1, 3, 4, 7, 9, 13, 16, 18, 20, 22, 24, 30-32, 35, 37, and 40 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 a method of treating mild cognitive impairment in a subject in need thereof comprising administering a compound selected from the group consisting of Compound 1a, 2a, 5a, and 6a to said subject, does not reasonably provide enablement for said method of treatment comprising administering any/all compounds within the genus of Formula (I), as instantly recited. 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.
21. The standard for determining whether the Specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? As recognized by the court in In re Wands, 858 F.2d 731 (Fed. Cir. 1988), that is still the standard to be applied, determined by consideration of the Wands factors (MPEP 2164.01(A)); namely, nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered, with the most relevant factors discussed below.
22. Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
In the instant case, the claimed invention pertains to a method for treating mild cognitive impairment in a subject in need thereof, comprising administering an effective amount of a compound of a compound of Formula (I) or a pharmaceutically acceptable salt thereof:
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23. The State of the Prior Art and the Level of Predictability in the Art: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains.” As discussed above, the instantly claimed invention pertains to a method for treating mild cognitive impairment and dementia, comprising: administering a therapeutically effective dosage of a composition to a patient in need, wherein the composition comprises: any cholinesterase inhibitor; and any serotonin and norepinephrine reuptake inhibitor (SNRI), (and optionally further comprising any N-methyl-D-aspartate receptor modulator).
24. At the time the instant application was filed, it would have been known by those of ordinary skill in the art that there is no single test for mild cognitive impairment (MCI), and diagnosis is often made by performing physical and neurological exams, as well as by ruling out morbidities with similar symptoms (see ClevelandClinic.org, page 3). Cleveland Clinic teaches that MCI is complex and its progression is often unpredictable:
“MCI may represent early stages of neurodegenerative disease. That is to say, it may be a sign of a condition that’s damaging your nervous system and brain — like Alzheimer’s disease or Parkinson’s disease. In those cases, MCI can, and often will, progress into dementia.
Other times, MCI isn’t related to neurodegenerative disease at all. It can stem from a wide range of concerns, including:
Brain injuries
Chronic conditions, like diabetes or high blood pressure
Sleep or mood disorders
Medication side effects.” (Cleveland Clinic, pages 1-2).
This low level of predictability is not surprising considering that Cleveland Clinic teaches that MCI is measured on a spectrum and progression varies from patient to patient, wherein symptoms may improve in some patients following treatment, or can worsen in patients already suffering from Alzheimer’s disease or other forms of dementia. Cleveland Clinic goes on to teach that treatment for MCI depends on the cause, and is often symptom-dependent, such as treating for depression or sleep apnea.
Thus it is not predictable from the specification or from the prior art that the administration of a compound embraced by the instant claims effectively treats mild cognitive impairment.
25. The Relative Skill of those in the Art: as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed.” The level of skill to practice the instantly claimed invention is high and requires a variety of skills usually found in institutions that employ highly trained and skilled scientists and/or physicians to carry out these tasks.
26. The Amount of Direction Provided by the Inventor / Existence of Working Examples: The amount of direction provided by the Applicant is considered to be determined by the Specification and the working examples. In the instant case, the instant Specification discloses only approximately 54 structurally related compound species within formula (I) in the synthesis examples of Compounds 1-54 at pages 60-99.
27. The instant Specification provides data demonstrating the potency of certain exemplary compounds towards HGF/MET in vitro in Example B1; demonstrates cell scattering behavior of MDCK cells following HGF treatment with certain exemplary compounds in Example B2; provides a solubility assay in Example B3; provides a permeability assay in Example B4; provides a cytotoxicity assay in Example B5; provides an in vitro stability assay in Example B6; demonstrates in vivo pharmacokinetics in Example B7; provides oral availability in Example B8; demonstrates non-specific protein binding in Example B9; demonstrates in vivo tissue distribution in Example B10 (see pages 99-113); and demonstrates the ability of just one compound (1a) to provide protection from neurotoxicity in vitro in Example B12. The only in vivo efficacy studies are provided in Example B11, wherein just two compounds (Compounds 2a and 6a) demonstrate the ability to reverse scopolamine-induced spatial memory deficits in rats (Table 12 and pages 113-115), and in Example B13, wherein just two compounds (Compounds 1a and 5a) demonstrate the ability to protect against scopolamine-induced cognitive impairment (pages 115-117).
28. Scope or Breadth of the Claims: As stated in MPEP 2164.01(c), “[w]hen a compound or composition claim is limited by a particular use, enablement of that claim should be evaluated based on that limitation.” Thus, as stated in MPEP 2164.08, “[t]he focus of the examination inquiry is whether everything within the scope of the claim is enabled” (emphasis added). Indeed, 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 (Fed. Cir. 1993) (emphasis added). At the same time, however, it is also recognized that not everything necessary to practice the invention need be disclosed. Nor is it necessary that an Applicant test all the embodiments of his invention. In re Angstadt, 537 F.2d 498 (CCPA 1976) (emphasis added). In fact, as stated by the court in In re Buchner, 929 F.2d 660 (Fed. Cir. 1991), a patent need not teach, and preferably omits, what is well known in the art.
29. Accordingly, for purposes of enablement, the relevant concern is whether the enablement provided to one skilled in the art by the disclosure is commensurate in scope with the protection sought by the claims. Thus, while “a patent application is entitled to claim his invention generically” it is necessary that “he provide a disclosure sufficient to enable one skilled in the art to carry out the invention commensurate with the scope of his claims". Amgen, Inc, v. Chugai Pharmaceutical Co., Ltd. (Fed. Cir. 1991).
30. The claims are drawn to a method of treating mild cognitive impairment in a subject in need thereof, comprising administering an effective amount of a compound of Formula (I):
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or a pharmaceutically acceptable salt thereof. In the instant case, it is evident that the genus of compounds embraced by formula (I) has substantial variance, i.e., the moiety R3 alone can be C2-C6 alkyl or any 5- to 10-membered heteroarylalkyl, and R4 can be any C6-C10 aryl or 5- to 10-membered heterocyclyl or 5- to 10- membered heteroaryl. For example, Formula (I) embraces Compound 25:
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and Compound 44:
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which bear little structural resemblance to one another. Therefore, it is evident that the genus of compounds embraced by Formula (I) is virtually without limit, embracing hundreds of millions of potential compounds.
31. It is also noted that Applicant fails to recite administering the compound of Formula (I) to “the subject” in the body of claim 1, such that the claims presently embrace administering an effective amount of said compound to any subject or in an in vitro culture, rather than limiting to the subject in need of treatment.
As such, the claim is extremely broad with respect to the disclosure.
32. Amount of Experimentation Necessary: In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the invention as claimed. As discussed above, the claims are drawn to a method of treating mild cognitive impairment comprising administering an effective amount of a compound of Formula (I):
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or a pharmaceutically acceptable salt thereof. As discussed in paragraphs “26” and “27” above, the nature of the instant invention considered to be one of extreme complexity. In the instant case, this complexity is exacerbated by the broadness of the genus of claimed compounds with respect to the disclosure since the potential compounds embraced by the claims include hundreds of millions of possible compound species, whereas the instant Specification discloses only 54 such species and demonstrates only four compounds exerting the desired activity of modulating HGF for the treatment of mild cognitive impairment. Although the relative skill of those in the art to which the invention pertains is high, the state of the art and unpredictability within the art is such that even the most talented artisan could not reasonably predict which of the hundreds of thousands of possible combinations encompassed by the claims would exert the alleged activity based on the limited disclosure. Given the unpredictability of treating MCI, as evidenced by Cleveland Clinic, it is highly unpredictable whether any compound of Formula (I) based on the instant disclosure would, in fact, be usable. Whether the other compounds would be usable is even less predictable. As such, the only way to ascertain which of the hundreds of millions of compounds encompassed by the claims are usable based on the limited disclosure would require undue experimentation. That is, the only way one skilled in the art is enabled to use the entire scope of the claim based on the instant disclosure entails undue experimentation.
Claim Rejections - 35 USC § 103
33. 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.
34. 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.
35. 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.
36. Claims 1, 3, 4, 7, 13, 20, 22, 24, 31, and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Kahn et al., U.S. Pat. No. 7,598,253 B2, in view of Alzheimer’s.gov (internet archive wayback machine webpage printout of https://www.alzheimers.gov/alzheimers-dementias/mild-cognitive-impairment, captured February 25, 2021).
Claim 1 is drawn to a method of treating mild cognitive impairment in a subject in need thereof, comprising administering an effective amount of a compound of Formula (I)
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, more specifically a compound wherein R1a and R1b are hydrogen; R2 is oxo; R3 is C6 aryl-alkyl (i.e., phenyl-ethyl); R4 is C6 aryl substituted by hydroxy (i.e., 4-hydroxyphenyl); L is –(CRaRb)m- wherein Ra and Rb are each hydrogen and m is 2 (i.e., –(CH2)2-); R6 is hydrogen; R7 is oxo; and n is 0, which is readable on claims 3, 7, 13, 20, 22, 24, 31 and 35.
37. Kahn et al. disclose a genus of functionally related reverse-turn mimetic compounds, and specifically teach the following compound 1a:
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(see columns 28-29), which is the same as a species of Applicant’s instant Formula (I) wherein R1a and R1b are hydrogen; R2 is oxo; R3 is phenyl-ethyl; R4 is 4-hydroxyphenyl; L is–(CH2)2-; R6 is hydrogen; R7 is oxo; and n is 0.
Kahn et al. go on to teach that:
“the compounds of this invention may be administered to a warm-blooded animal that has been diagnosed with, or is at risk of developing a condition selected from … Alzheimer's disease” [emphasis added] (paragraph [0082]).
38. Kahn et al. do not teach the treatment of mild cognitive impairment.
39. Yet, Alzheimer’s.gov teaches that:
“People with MCI are at a greater risk of developing Alzheimer’s disease or a related dementia.” (page 2, second paragraph).
40. As such, one of skill in the art would recognize that a patient at risk of developing Alzheimer’s disease (i.e., the patient population taught by Kahn et al.) meets the limitation of a patient suffering from mild cognitive impairment.
41. Thus, in view of the combined art of record, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to administer compound Ia of Kahn et al. to a patient in need of treatment for mild cognitive impairment, with a reasonable expectation of success.
As such, claims 1, 3, 7, 13, 20, 22, 24, 31 and 35 are prima facie obvious.
Claim 4 is drawn to claim 1, wherein L is–(CRaRb)m- wherein Ra and Rb are each hydrogen and m is 1.
42. Kahn et al. disclose compound 1a, wherein the moiety corresponding to “L” is –(CRaRb)m- wherein Ra and Rb are each hydrogen and m is 2, i.e., –(CH2)2-, which differs from the compound of claim 4 by the addition of one -CH2- group.
43. Yet, one skilled in the art would have been motivated before the effective filing date of the claimed invention to modify compound 1a by removing a -CH2- group from the moiety corresponding to “L,” i.e., preparing a compound comprising a methyl group rather than an ethyl group, with the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See also MPEP 2144.09, I and II.
Thus one of skill in the art before the effective filing date of the claimed invention would have known that compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
Therefore, claim 4 is prima facie obvious.
44. Claim 40 is rejected under 35 U.S.C. 103 as being unpatentable over Kahn et al., U.S. Pat. No. 7,598,253 B2, in view of Alzheimer’s.gov (internet archive wayback machine webpage printout of https://www.alzheimers.gov/alzheimers-dementias/mild-cognitive-impairment, captured February 25, 2021), as applied to claims 1, 3, 4, 7, 13, 20, 22, 24, 31, and 35, above, and further in view of Steenbergen et al., (Cognitive, Affective and Behavioral Neuroscience 2019).
Claim 1 is addressed in detail, above.
Claim 40 is drawn to claim 1, wherein the method slows progression of dementia in the subject, or improves cognitive function or slows progression of cognitive dysfunction in the subject.
45. Kahn et al. in view of Alzheimer’s.gov teach a genus of reverse turn mimetic compounds, in particular compound 1a, wherein said genus possesses opioid receptor modulating activity in Examples 9 and 10 (pages ___, and suggest said compounds for the treatment of a patient at risk of developing Alzheimer’s disease (i.e., a patient with mild cognitive impairment), but do not teach the improvement in cognitive function.
46. Yet, Steenbergen et al. teach the effect of opioid modulators on cognitive function, and specifically teach that opioid receptor modulators improve cognitive function:
“At lower doses opioids can improve cognitive function, and the working hypothesis proposed suggests that these effects are driven by opioid-induced reduction of aversive arousal.”
(page 452, left column, under Conclusions).
47. Therefore, one skilled in the art before the effective filing date of the claimed invention would have been motivated to treat a patient at risk of Alzheimer’s by administering compound 1a to the patient, wherein said patient suffers from mild cognitive impairment, and would expect that the treatment would improve cognitive function in said patient, with a reasonable expectation of success.
As such, claim 40 is prima facie obvious.
Double Patenting
48. 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.
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49. Claims 1, 3, 4, 7, 9, 13, 16, 18, 20, 22, 24, 30-32, 35, 37, 39, 40 and 43-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4, 7, 9, 18, 20, 22, 24, 26, 30, 39, 40, and 52-62 of copending Application No. 18/032,918 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because Applicant’s instant claims are drawn to a method of treating cognitive impairment in a subject in need thereof, comprising administering a compound of Formula (I):
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, wherein L can be -C(=O)-; -(CRaRb)m- wherein Ra and Rb are hydrogen and m is 1; R1a and R1b can be hydrogen or C1-C6 alkyl, wherein C1-C6 alkyl can be optionally substituted by -CO2H; R3 is C2-C6 alkyl; C3-C6 alkenyl; or C3-C12 cycloalkylalkyl; R4 can be C6 aryl or 6 membered heteroaryl containing a nitrogen, which can be substituted with 1-5 substituents selected from C1-C6 haloalkyl, hydroxyl, and halogen.
50. The claims of 18/032,918 are drawn to a compound of Formula (V):
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, or a pharmaceutically acceptable salt thereof, wherein:
L is -C(=O)- or -CH2-; R1a and R1b are independently H or C1-C3 alkyl optionally substituted with -CO2H; R3 is C4-C5 alkyl, C4-C5 alkenyl, or C1-C3 alkyl substituted with C3-C5 cycloalkyl; and R4 is phenyl or pyridyl substituted with 1-3 substituents selected from -CF3, -OCHF2, -OH, fluoro, and chloro
51. Therefore, the genus of compounds of instant formula (I) fully embraces the subgenus of compounds of formula (V) recited by the claims of 18/032,918. The reference claims of the ‘918 application recite a method of using compounds of Formula (I) to treat neurodegenerative disorders, including cognitive dysfunction. The instant claims simply claim the methods of treating cognitive impairment (aka cognitive dysfunction) that was disclosed in the specification of the ‘918 copending application (please see paragraphs [0200]-[0207] of the ‘918 application for discussions of treating neurodegenerative disorders, treating cognitive dysfunction, slowing the progression of dementia, etc).
In Sun Pharmaceutical Industries, Ltd, v. Eli Lilly And Company (2010), the district court followed the double patenting analysis of the Geneva line of cases, which address the situation in which an earlier patent claims a compound, disclosing the utility of that compound in the specification, and a later patent claims a method of using that compound for a particular use described in the specification of the earlier patent. In making this ruling, the district court relied on the Federal Circuit’s earlier rulings on double patenting of compound claims, mainly Geneva Pharmaceuticals, Inc, v. GlaxoSmithKline PLC, 349 F. 3d 1373 (Fed. Cir. 2003), and Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc., 518 F.3d 1353 (Fed. Cir. 2008). In both of these cases, the Federal Circuit found claims of a later patent invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent. The cases also established that in determining the scope of compound claims for a double patenting rejection one must look to the specification to interpret the utility of the compound.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
52. Claims 1, 3, 4, 7, 9, 13, 16, 18, 20, 22, 24, 30-32, 35, 37, 39, 40 and 43-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 7, 9, 18, 20, 21, 30, 31, 37, 40, 41, 45, and 64-68 of copending Application No. 18/858,864 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because Applicant’s instant claims are drawn to a method of treating cognitive impairment in a subject in need thereof, comprising administering a compound of Formula (I):
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.
53. The claims of 18/858,864 are drawn to a method of treating a neuroinflammatory condition in a subject in need thereof, comprising administering an effective amount of a compound of Formula (I):
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, or a pharmaceutically acceptable salt, isotopic form, or stereoisomer thereof, wherein the genus of Formula (I) is identical to the genus of compounds that are instantly recited by Applicant.
54. Therefore, the genus of compounds of instant Formula (I) is the same as the genus of compounds of Formula (I) recited by the claims of copending application 18/858,864. The reference claims recite a method of using compounds of Formula (I) to treat a neuroinflammatory disorder, and the Specification of the ‘864 application teaches that: “Compound A19, Compound la, and Compound 5a reversed the LPS-induced cognitive disruption in the mouse T-maze assay,” and that, “[a]nimals treated with test compounds have improvement in one or more tests of cognitive function during the study,” (paragraphs [0341] and [0343]). Thus, by reversing cognitive disruption and improving cognitive function, one is necessarily treating cognitive impairment. The instant claims simply claim a method of treating cognitive impairment (aka improving cognitive function) that was disclosed in the specification of the ‘864 copending application.
55. Please refer to MPEP § 804 II.B.2(a), i.e. the specification of the reference patent may be relied upon to properly construe the scope of the reference claim, and “may be considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the patent.” See also In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970): those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
56. In conclusion, claims 1, 3, 4, 7, 9, 13, 16, 18, 20, 22, 24, 30-32, 35, 37, 39, 40 and 43-53 are present in the application. Claims 1, 3, 4, 7, 9, 13, 16, 18, 20, 22, 24, 30-32, 35, 37, and 40 are rejected. No claim is presently allowed.
57. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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/JANET L COPPINS/Examiner, Art Unit 1628
/Rayna Rodriguez/Primary Examiner, Art Unit 1628
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