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
2. Applicant’s amendment and response, submitted July 2, 2026 has been reviewed by the examiner and entered of record in the file.
3. Claims 1, 2, 4-7, 9 and 10 are amended. Claims 3 and 8 are canceled.
4. Claims 1, 2, 4-7, 9 and 10 are under examination and are the subject of this office action.
Priority
5. Applicant’s submission of the certified English language translation of foreign priority CN Application No. 202110901146.3 is accepted.
Information Disclosure Statement
6. The information disclosure statement (IDS) submitted on July 2, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner, please refer to the signed copy of Applicant’s PTO-1449 form, attached herewith.
Specification
7. The abstract of the disclosure was previously objected to for failing to provide the use of the compound of Formula I for preparing a medication for preventing or treating an autoimmune disease or a related inflammatory skin disease.
8. In view of Applicant’s submission of the corrected abstract, the previous objection is withdrawn.
9. The disclosure was previously objected to because of the following informalities:
(a) The reaction scheme for synthesizing compound 7 is blurry/ unclear and the compound structures are difficult to ascertain (paragraph [0070]).
(b) The reaction scheme for synthesizing compound 9 is blurry/ unclear and the compound structures are difficult to ascertain (paragraph [0082]).
(c) The reaction scheme for synthesizing compound 10 is blurry/ unclear and the compound structures are difficult to ascertain (paragraph [0088]).
10. In view of Applicant’s submission of the substitute Specification, wherein paragraphs [0070], [0082], and [0088] are replaced with clear reaction schemes, the previous objections are withdrawn.
Previous Claim Rejections - 35 USC § 112(b)
11. Claims 1-10 were previously 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.
12. Claim 1 was previously rejected as being unclear in the following aspects:
(a) Claim 1 previously recited “[a] JAK inhibitor with high oral bioavailability, wherein the JAK inhibitor comprises a compound according to Formula I, or a stereoisomer, geometric isomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof as an active ingredient,” however it was not clear if the JAK inhibitor is the compound of Formula I, or if the JAK inhibitor is a composition comprising the compound of Formula I.
(b) Claim 1 previously recited the term “high oral bioavailability” in line 1, which is a relative term that renders the claim indefinite.
In view of Applicant’s amendment to claim 1 to delete the recitation of “[a] JAK inhibitor with high oral bioavailability, wherein the JAK inhibitor comprises….” from the preamble, the previous indefiniteness rejection is withdrawn.
13. Claim 6 was previously rejected as being unclear in the following aspects:
(a) Claim 6 was previously drafted in terms of an improper product/use, i.e., the claim recited the “use of the compound of Formula I… in preparation of a medication,” [emphasis added].
(b) Claim 6 was also rejected as being incomplete regarding the recitation of the “use of the compound of Formula I,” in line 1, because the claim fails to recite Formula I within the claim itself and does not refer back to a preceding claim.
(c) Claim 6 previously recited the term “related inflammatory skin disease” wherein “related” is a relative term which renders the claim indefinite.
14. In view of Applicant’s amendatory changes to claim 6 to draft the claim as a method of treatment rather than a “use,” and to delete the recitation of “Formula I” as well as the term “related,” the previous indefiniteness rejection is withdrawn.
15. Claim 7 was previously rejected regarding the phrase "wherein the autoimmune disease is at least one of …" and Claim 8 was previously rejected regarding the phrase “wherein the related skin inflammatory disease is at least one of …."
16. In view of the amendment to claim 7 to delete the text “at least one of” and the cancelation of claim 8, previous indefiniteness rejections of said claims are withdrawn.
Previous Claim Rejections - 35 USC § 101
17. Claims 6-10 were previously rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter, regarding the recitation of a “use,” because the claimed invention of a “use” is not supported by either a credible asserted utility or a well-established utility for the reasons set forth above, one skilled in the art clearly would not know how to use the claimed invention.
18. In view of Applicant’s amendment to claim 6 to draft the claim in terms of method of treatment rather than a “use,” the previous rejection under 35 USC § 101 is withdrawn.
Previous 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, 2, 4-7, 9 and 10 remain 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 regarding the scope of compounds and alternatives according to the genus of Formula I. 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. In particular, support cannot be found for the full scope of compounds of Formula I, or their stereoisomers, geometric isomers, tautomers, hydrates, or solvates, as instantly recited by the claims.
21. This rejection has been modified as necessitated by Applicant’s amendment to the claims.
22. 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. The problem is especially acute with genus claims that uses open-ended language such as “or an isotopically labeled derivative thereof.” In such a case, the claim simply recites the generic “derivative,” and may do so without describing species that achieve that result. But the specification must demonstrate that the Applicant has made a generic invention that achieves the claimed result and do so by showing that the Applicant has invented sufficient alternative species to support the claim to the generically-defined genus.
23. 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.
24. 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 to carry out these tasks.
25. Partial structure; Physical and/or chemical properties; and Functional characteristics: The claims are drawn to a JAK inhibitor comprising a compound according to the genus 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. The claimed genus of Formula I is extremely broad, embracing hundreds of thousands of compounds which bear little structural overlap with one another, i.e., presently the genus of compounds according to Formula I embraces compound species wherein the variable R3 can be a substituted or unsubstituted 5-6 membered aryl or heteroaryl selected from the group consisting of a phenyl group, pyridyl group, pyrimidyl group, pyrazolyl group, pyrrolyl group, imidazolyl group, pyrazinyl group, and a pyridazinyl group.
26. The instant compounds are alleged by the Specification to be JAK inhibitors, which may be useful as therapeutics for the treatment of autoimmune-related inflammatory diseases (paragraph [0008]).
27. Method of making: It is evident that the genus of compounds embraced by the claims has substantial variance, for example, the variable R3 can be a substituted or unsubstituted 5-6 membered aryl or heteroaryl selected from the group consisting of a phenyl group, pyridyl group, pyrimidyl group, pyrazolyl group, pyrrolyl group, imidazolyl group, pyrazinyl group, and a pyridazinyl group, such that the scope of compounds of Formula I recited by claim 1 embraces hundreds of compound species, if not thousands, or pharmaceutically acceptable salts thereof. Yet, the instant Specification discloses the preparation of only ten compound species according to Formula I as broadly recited by the claims: see the Syntheses of compounds 1-5 (pages 8-10) and comparative examples 6-10 (pages 11-16), wherein in Compounds 1 and 6, R1 is N and R3 is pyrazolyl; in Compounds 2, 3, 7, and 8; R1 is C and R3 is pyrazolyl; in Compounds 4, 5, 9 and 10, R1 is C and R3 is phenyl.
28. 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 claim. 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 the preparation of just ten compounds (i.e., Compounds 1-10) does not adequately describe a genus embracing hundreds or thousands of possible compounds. That is, the Specification does not disclose a sufficient variety of species to reflect the breadth of the possible compound selections recited in the claims.
29. 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). The fields of biology and chemistry are considered “unpredictable” because the complexity and unpredictability of chemical and biological interactions can make it difficult to understand the exact properties of an invention. A person of ordinary skill in the art from the specification or from the prior art cannot predict the pharmacological effects of administration of the instant formulation in subjects in regards to prevention of pain. The pharmaceutical industry is the prototypical example of a highly unpredictable field. Pfizer v. Teva Pharm., 482 F.Supp.2d 390, 413 (D.N.J. 2007); 2 Chisum on Patents § 5.04.
30. 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.) 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).
31. 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.").
32. Accordingly, it is deemed that the specification fails to provide adequate written description for the full scope of compounds of Formula I or a pharmaceutically acceptable salt, thereof, as presently embraced by 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.
As such, claims 1, 2, 4-7, 9 and 10 are rejected.
Response to Arguments
33. Applicant traverses the written description rejection under 35 U.S.C. 112(a), and argues that as a result of the claim amendments to delete the recitation of any isomers, and to further define the 5- or 6- membered aryl or heteroaryl group recited in the definition of R3, that claim 1 is now fully supported by the Specification.
34. Applicant's arguments have been fully considered but they are not persuasive. While Applicant’s amendments delete the features related to isomers and limit the variable R3 such that R3 is substituted or unsubstituted 5-6 membered aryl or heteroaryl selected from the group consisting of a phenyl group, pyridyl group, pyrimidyl group, pyrazolyl group, pyrrolyl group, imidazolyl group, pyrazinyl group, and a pyridazinyl group, it is noted that the scope of compounds of Formula I recited by claim 1 still embraces hundreds of compound species or pharmaceutically acceptable salts thereof, if not thousands of compound species. Yet, the instant Specification discloses the preparation of only ten compound species according to Formula I as broadly recited by the claims: see the Syntheses of compounds 1-5 (pages 8-10) and comparative examples 6-10 (pages 11-16), wherein in Compounds 1 and 6, R1 is N and R3 is pyrazolyl; in Compounds 2, 3, 7, and 8; R1 is C and R3 is pyrazolyl; in Compounds 4, 5, 9 and 10, R1 is C and R3 is phenyl. Thus, the Specification has not shown support for all of the possible alternatives of Formula I, e.g., wherein the R3 moiety is other than phenyl or pyrazolyl (and the ring comprising R1 is either phenyl or pyridyl for each R3 alternative ring, as well as the possible R2 moieties for each R3 ring option).
As such, Applicant has not demonstrated possession of the substantial variance embraced within the genus of compounds of Formula I, and the written description rejection is maintained.
35. Claims 6, 7, 9 and 10 remain 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 preparing Compounds 1-5 and compositions thereof (pages 8-10) having improved oral bioavailability over Compounds 6-10 (pages 15-16), is not enabled for a method of treating the full scope of autoimmune diseases or inflammatory skin diseases presently embraced by the claims. 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.
36. This rejection has been modified as a result of Applicant’s amendments to the claims.
37. 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.
38. 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.”
39. In the instant case, claim 6 is drawn to a method of treating an autoimmune disease or an inflammatory skin disorder in a subject in need thereof, comprising administering a compound of claim 1 to the subject, wherein the inflammatory skin disease is selected from the group consisting of psoriasis, autoimmune-related vasculitis, scleroderma, dermatomyositis, acrodermatitis enteropathica, hidradenitis suppurativa, lichen planus, vitiligo, cutaneous lupus erythematosus, and lichen sclerosus et atrophicus. Claim 7 limits the autoimmune disease to an autoimmune disease selected from the group consisting of rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, Sjogren's syndrome, dermatomyositis, ankylosing spondylitis, multiple sclerosis, Behcet's disease, severe COVID-19 pneumonia, Reiter's syndrome, and uveitis.
40. 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” and, 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.”
As described above, the claims are drawn to a method of treating an autoimmune disease or an inflammatory skin disease.
41. The state of the art regarding autoimmune diseases is that there are more than 100 different autoimmune diseases, which can affect almost any tissue or organ in the body, including joints, muscles, skin, blood vessels, digestive system, endocrine system, and the nervous system, and can include: Rheumatoid arthritis (RA), systemic lupus erythematosus, myositis, Crohn’s disease, Celiac disease, Ulcerative colitis, Autoimmune gastritis, Type 1 diabetes, Addison’s disease, Hashimoto’s thyroiditis, Graves’ disease, Multiple sclerosis (MS), Myasthenia gravis (MG), Guillain-Barré syndrome, Chronic inflammatory demyelinating polyneuropathy (CIPD); as well as skin inflammatory diseases including Sjögren’s syndrome, Psoriasis, Psoriatic arthritis, Dermatomyositis, Scleroderma, Vitiligo, Vasculitis, Rheumatoid vasculitis, and Urticarial vasculitis, (webpage printout of ClevelandClinic.org Autoimmune Diseases: Types, Symptoms & Treatments, pp.1-2).
42. In addition to the above diseases, Applicant discloses autoimmune diseases that also include inflammatory bowel disease, ankylosing spondylitis, multiple sclerosis, Behcet's disease, severe COVID-19 pneumonia, Reiter's syndrome, and uveitis; and related inflammatory skin diseases including the above list as well as acrodermatitis enteropathica, hidradenitis suppurativa, lichen planus, cutaneous lupus erythematosus, and lichen sclerosus et atrophicus (Specification, paragraph [0046]).
Thus, the recited autoimmune diseases embraced by claim 6 embrace a broad spectrum of morbidity and mortality.
43. Virtanen et al. teach that JAK kinases are effective therapeutic targets in rheumatic and other inflammatory diseases, however, inhibition of JAK kinase activity does not translate directly into cellular inhibition of JAK/STAT signaling (abstract: Conclusion). Virtanen et al. go on to teach that this unpredictability impacts less selective JAK inhibitors: “Highly specific inhibitors can achieve more predictable responses and have less undesired side effects by having reduced off targets, whereas a wider inhibitory range can increase clinical efficacy (but possibly also side effects) by inhibiting several targets” (page 2057, right column, under “Discussion”).
44. This unpredictability is certainly true in the case of treating the vast scope of autoimmune diseases embraced by the claims, which, as disclosed by ClevelandClinic.org above, are complex and varied in etiology as well as severity of pathology depending on the system(s) affected in the body, i.e., muscles, skin, blood vessels, digestive system, endocrine system, and the nervous system, (Page 1 of ClevelandClinic.org).
45. There is no question Applicant’s instant JAK inhibitor compounds may play a role in future methods of treating certain of the aforementioned types of autoimmune or skin inflammatory diseases. What is disputed is the claim that the recited method could be employed by one skilled in the art at the effective filing date of the claimed invention and used as treatment for any/ all types and kinds of autoimmune diseases embraced by claims 6, 9, and 10, as well as the specific diseases recited in claim 7, and inflammatory skin diseases of claim 6, without undue experimentation. There is simply no evidence to be found in the literature suggesting that Applicant’s compounds are capable of being used in the manner recited. In essence, there is no absolute predictability in pharmacology, even with compounds whose properties have been determined, despite the extraordinarily high skill possessed by the ordinary artisan.
46. Hence, in the absence of a showing of correlation between all types and kinds of autoimmune diseases and inflammatory skin diseases embraced by the claims as capable of being treated by any of the compounds or pharmaceutical salts thereof recited in claim 1, one of skill in the art is unable to fully predict possible results from the administration of the compound(s) of the instant claims for treating the scope of autoimmune diseases and inflammatory skin pathologies encompassed by the claims.
47. As such, one of skill in the art would be unable to fully predict the therapeutic effects of administering any/all JAK inhibitor(s) embraced by Formula I for the treatment of the recited autoimmune diseases and inflammatory skin diseases, and/or the multitude of types of autoimmune diseases taught by ClevelandClinic.org, as embraced by the instant claims.
48. Relative Skill of those in the Art: The level of skill in the art of one tasked with treating or preventing any type of autoimmune disease or disorder in a subject, i.e., scientists or physicians, represent one of ordinary skill in the art.
49. 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, Applicant provides no working examples demonstrating the in vitro or in vivo effect(s) of any compound of Formula I, on any autoimmune disease or inflammatory skin disease. The only guidance provided at all is an oral pharmacokinetic parameter study in rats to compare Compounds 1 to 5 with parent Compounds 6 to 10 (having similar structures) wherein pharmacokinetic (PK) tests were conducted to compare the PK parameters of Compounds 1-10 in Sprague Dawley (SD) rats with a single oral dose, wherein Compounds 1-5 demonstrated improved oral bioavailability (paragraph [0096]). As such, the Specification does not support the broad claim of treatment of any of the multitude of types of autoimmune diseases and/or inflammatory skin diseases embraced by the claims.
50. 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). 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).
51. 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.
52. Accordingly, for purposes of enablement, the relevant concern is whether the scope of 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). As noted by the court in In re Fisher, 427 F.2d 833 (CCPA 1970), the scope of enablement must bear a “reasonable correlation” to the scope of the claims. As stated in MPEP 2164.08, resolution of this concern requires two stages of inquiry: “[t]he first is to determine how broad the claim is with respect to the disclosure. The entire claim must be considered. The second inquiry is to determine if one skilled in the art is enabled to make and use the entire scope of the claim without undue experimentation”.
53. As to the first inquiry, as discussed above, the claims are drawn to the use of a compound of Formula I or pharmaceutically acceptable salt thereof treating the full scope of autoimmune disease(s) and/or inflammatory skin disease(s) embraced by the claims.
54. Considering that the autoimmune diseases to be treated include but are not limited to rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, Sjogren's syndrome, dermatomyositis, ankylosing spondylitis, multiple sclerosis, Behcet's disease, severe COVID-19 pneumonia, Reiter's syndrome, uveitis; and the related inflammatory skin diseases are selected from psoriasis, autoimmune-related vasculitis, scleroderma, dermatomyositis, acrodermatitis enteropathica, hidradenitis suppurativa, lichen planus, vitiligo, cutaneous lupus erythematosus, lichen sclerosus et atrophicus, and the like, using a compound according to Formula I, it is evident that the claims are broad. Yet, as discussed above, the instant Specification discloses only one assay comparing the oral bioavailability of compounds 1-5 with parent compounds 6-10, and fails to disclose any examples of treating or mitigating any autoimmune disease or inflammatory skin disease whatsoever. As such, the claim is extremely broad with respect to the disclosure. The second inquiry is discussed in detail below.
55. 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 entire scope of the invention as claimed. As discussed above, the claims are drawn to the use of a compound of Formula I or pharmaceutically acceptable salt thereof treating the full scope of autoimmune disease(s) and/or inflammatory skin disease(s) embraced by the claims.
Since identifying any autoimmune or inflammatory skin disease that is capable of being treated by administering any of the genus of recited compounds or alternatives is extremely complex, the nature of the instant invention considered to be one of extreme complexity. In the instant case, this complexity is exacerbated by the challenges of treating any/ all types of autoimmune and/or inflammatory skin disease as well as the breath of the scope of compounds of Formula I. 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 what autoimmune disease or inflammatory skin disease encompassed by the claims would be treatable based on the limited disclosure which fails to provide any working examples.
56. To overcome this rejection, Applicant should narrow the scope of the claims such that they bear a reasonable correlation with the disclosure.
Response to Arguments
57. Applicant traverses the rejection, and amends claim 6 to remove "prevention", "Reiter's syndrome", and "acrodermatitis enteropathica." Applicant argues that the instant specification shows that the claimed compounds exhibit inhibitory activity against JAK kinases, and argues that the submitted references demonstrate that JAK inhibitors can be used for the treatment of the claimed autoimmune diseases and related inflammatory skin disorders, wherein Reference 1 (i.e., SCHWARTZ et al.), teaches that certain JAK inhibitors block the JAK-STAT pathway and are validated for the treatment of various autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, Systemic lupus erythematosus, scleroderma, Sjogren's syndrome, dermatomyositis, ankylosing spondylitis, multiple sclerosis, Behcet's disease, autoimmune-related vasculitis, psoriasis, vitiligo, and cutaneous lupus erythematosus. Reference 3 (i.e., DAMSKY et al.) suggests that JAK inhibition might be a viable strategy to treat Lichen planus. Reference 4 (i.e., DU et al.) and Reference 5 (i.e., KEELING et al.) suggest JAK inhibitors for the treatment of uveitis. Reference 6 (i.e., DEL DUCA et al.) suggest JAK inhibitors for the treatment of hidradenitis suppurativa (HS). Reference 7 (i.e., SATARKER et al.) teaches that severe COVID-19 pneumonia can be treated by inhibiting JAK pathways. Reference 8 (i.e., SOLIMANI et al.) suggests that oral/topical JAK inhibitors are effective for treating lichen sclerosus).
58. Applicant's arguments have been fully considered but they are not persuasive. Applicant argues that there is a well-understood relationship between JAK inhibition and the treatment of autoimmune and inflammatory skin pathologies, and references the eight articles included with the IDS on July 2, 2026. The Schwartz et al. article teaches that type I/II cytokines rely on the JAK-STAT pathway to mediate autoimmune pathology, wherein certain JAK inhibitors are implicated in a few autoimmune disorders. The remaining articles each discuss that specific JAK inhibitors are implicated in one or two autoimmune diseases each, wherein Applicant alleges that one skilled in the art would understand that JAK inhibiting compounds as a class would treat each of said autoimmune and inflammatory skin pathologies, and based upon these teachings, would be enabled to do so.
59. The Examiner respectfully disagrees, since a teaching or suggestion by a prior art reference(s) does not automatically correspond to enablement of the instant claims. In the referenced article, Schwartz et al. broadly discuss autoimmune disorders and suggest specific JAK inhibitors as a therapeutic strategy for certain specific diseases/disorders. Schwartz et al. also discuss the complex and unpredictable nature autoimmune disorders and the resulting challenges in treating said disorders(see abstract), and go on to teach that JAK inhibitors are not without side effects that are directly linked to the mechanism of blocking JAK-dependent cytokine signaling, including increased risk of infection, increases in lipid levels, and the potential role in malignant tumor development (see pages 8-9).
Applicant’s instant Specification provides only one assay comparing the oral bioavailability of compounds 1-5 with parent compounds 6-10, and fails to disclose any examples of treating or mitigating any autoimmune disease or inflammatory skin disease whatsoever, but does not support the claim of treating the recited broad scope of autoimmune and inflammatory skin pathologies.
Accordingly, the previously applied enablement rejection of claims 6, 7, 9 and 10 is maintained.
Previous Claim Rejections - 35 USC § 103
60. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
61. Claims 1, 4-7, 9 and 10 remain rejected under 35 U.S.C. 103 as being unpatentable over CN 110627775 A (published December 31, 2019, cited on Applicant’s IDS of February 6, 2024 with an English translation provided), in view of Rautio et al., Nature Reviews (2008).
Claim 1, as amended, is drawn to a compound of Formula I, or a pharmaceutically acceptable salt thereof,
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, wherein R1 is C or N; R2 is selected from
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(more specifically, the moiety:
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); R3 is selected from a 5 or 6 membered aryl or heteroaryl group that is optionally substituted, (more specifically the moiety:
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(claim 5)). As thus summarized, the invention reads on claims 1, 4 and 5.
Claim 6 is drawn to the treatment of an autoimmune disease or an inflammatory skin disease in a subject in need thereof, comprising administering a compound of a pharmaceutically acceptable salt thereof of claim 1 to the subject, wherein the inflammatory skin disease is selected from the group consisting of psoriasis, autoimmune-related vasculitis, scleroderma, dermatomyositis, acrodermatitis enteropathica, hidradenitis suppurativa, lichen planus, vitiligo, cutaneous lupus erythematosus, and lichen sclerosus et atrophicus.
Claim 7 is drawn to claim 6, and limits wherein the autoimmune disease is at least one of rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, Sjogren's syndrome, dermatomyositis, ankylosing spondylitis, multiple sclerosis, Behcet's disease, severe COVID-19 pneumonia, Reiter's syndrome, and uveitis.
62. CN 11067775 A discloses two small molecule compounds that are nearly the same as compound species of Applicant’s instant Formula I, specifically a compound having either a carbon or nitrogen substitution at the moiety corresponding to R1, the group
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at the moiety corresponding to R2, and a methyl-pyrazole group at the moiety corresponding to R3:
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and
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(pages 76 and 77 of the original document). The small molecule compounds TDM 180934 and TDM 180935 have the same activity as the instantly recited compounds, i.e., JAK kinase inhibitory activity, and are suitable for treating autoimmune diseases such as rheumatoid arthritis, ulcerative colitis, IBD, MS, and inflammatory skin diseases such as eczema, psoriasis, alopecia areata, leukoderma, lupus, lichen planus, lichen glossus, lichen sclerosis atrophicus, atopic dermatitis, and the like (see page 3 of the English translation, first paragraph under “Disclosure of the Invention” and page 5, lines 19-22).
63. The compounds TDM 180934 and TDM 180935 differ from Applicant’s instantly recited compounds because they are “parent drugs,” i.e., the nitrogen (N) attached to the phenyl or pyridyl ring is substituted by R2 and by Hydrogen, rather than by the recited pivaloylmethyl ester functional group:
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.
64. However, CN 11067775 A teaches the small molecule compounds of the invention include prodrugs thereof (see page 3 of the English translation, second paragraph under “Disclosure of the Invention”).
65. And, Rautio et al. teach the advantages of utilizing prodrugs in the pharmaceutical arts: a well-established strategy to improve physiochemical, biopharmaceutical and/or pharmacokinetic properties of pharmacologically potent compounds, increasing the usefulness of the active agent, wherein prodrugs increase solubility, improve absorption and distribution for organ or tissue specificity, enhance stability, make drugs temporarily non-toxic, and improve drug targeting, for example (page 255, first three paragraphs). Rautio et al. teach that esters are the most common prodrugs used (page 256, right column, under “Esters as prodrugs of carboxyl, hydroxyl, and thiol functionalities”), and go on to disclose several parent drugs having pivaloylmethyl ester functional groups, which is the same functional group attached to Applicant’s instantly recited compound:
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. In Table 1, Rautio et al. teach that the same pivaloyloxy-methyl-ester functional group significantly improved the oral bioavailability of ampicillin and adefovir prodrugs as compared to their parent drugs (page 257).
66. As such, it would have been prima facie obvious to one skilled in the art before the effective filing date of the claimed invention to modify the parent drugs TDM 180934 and/or TDM 180935, taught by CN 11067775 A, with a pivaloyloxy-methyl-ester functional group on the phenyl/pyridyl -NH moiety, in order to prepare a prodrug having improved physiochemical and pharmacological properties for the treatment of autoimmune and/or inflammatory skin diseases. One of skill in the art before the effective filing date of the claimed invention would have been motivated to prepare the instantly claimed pivaloyloxymethyl ester of TDM 180934 and/or TDM 180935, and would have had a reasonable expectation of successfully obtaining prodrugs having improved bioavailability.
Thus, claims 1 and 4-7 are prima facie obvious.
Claim 9 is drawn to the method of claim 6, wherein the medication is an orally administered medication. Claim 10 is drawn to the method of claim 9, wherein the orally administered medication is in a form of a tablet, a pill, a granule, a capsule, a lozenge or a liquid formulation.
67. CN110627775A additionally teaches that the JAK inhibitor compounds of the invention can be made into various dosage forms such as for oral administration, and that said compounds are suitable for oral administration (page 5 of the English translation, lines 13 and 21-22). And, Rautio et al. teach the improved oral bioavailability of prodrugs modified with the pivaloyloxymethyl ester moiety, for oral administration. Thus, one of skill in the art before the effective filing date of the claimed invention would have been motivated to prepare the instantly claimed pivaloyloxymethyl ester of TDM 180934 and/or TDM 180935 in the form of an orally administered medication, and would have had a reasonable expectation of successfully obtaining prodrugs having improved bioavailability.
As such, claims 9 and 10 are prima facie obvious.
Response to Arguments
68. Applicant traverses the obviousness rejections, and argues that the instant application showed that the claimed compound exhibits significantly improved oral bioavailability and reduced in vivo clearance rate compared to the Comparative Compound 6, which is compound TDM180395 in CN11067775. Applicant contends that this finding is not obvious in view of CN11067775 and Rautio et al. Applicant disagrees with the Action's assertion that a skilled person would have been motivated to combine CN11067775A and Rautio et al to arrive at the claimed invention because Rautio et al teaches that introduction of a pivaloyloxymethyl (POM) ester moiety can improve oral bioavailability. Applicant argues the following points:
(a) Applicant alleges that CN11067775A merely makes a general reference to the concept of "prodrug" in the claims, but does not disclose any specific modification sites, prodrug moieties, or strategies for prodrug design, and therefore CN11067775A provides no concrete or enabling guidance for implementing prodrug modifications.
Applicant argues that Rautio et al (pp. 256-257) lists numerous ester-type prodrug carriers capable of masking polar functional groups and improving oral bioavailability, wherein POM is only one among many possible acyloxymethyl-type double prodrug carriers disclosed therein (and other carriers of the same class include isopropoxycarbonyloxymethyl (POC)). Rautio et al also discloses various prodrug modification pathways such as simple alkyl esters and amino acid esters, all of which can enhance oral exposure. Applicant contends that in view of CN11067775A, a skilled person would have a wide range of possible modification groups and strategies to choose from, and the Action has not provided a reason why a skilled person would choose POM over other options to modify the compound taught by CN11067775A. Applicant alleges that the Action's assertions constitute a hindsight bias.
(b) Applicant argues that with respect to the POM group, Rautio et al only provides examples involving antibiotics and antiviral drugs, where the POM group is used to modify carboxyl or phosphate groups to improve oral absorption. Rautio et al does not teach or suggest applying the POM group to JAK inhibitors, nor does it provide any guidance to introduce POM at the imino position of phenyl or pyridyl ring in JAK inhibitors.
Applicant contends that neither CN11067775A nor Rautio et al. provides any teaching or suggestion directing a skilled person to the specific modification site (imino position of the phenyl/ pyridyl ring of the JAK inhibitor disclosed in CN11067775A) or the particular prodrug moiety (POM) employed in the present invention, without engaging in undue experimentation.
69. Applicant's arguments have been fully considered but they are not persuasive. In response to Applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, CN11067775 A specifically teaches the active parent compound TDM180395 which has two sites of possible cleavage for prodrug activation, i.e., the -NH moieties. Rautio et al. is relied upon for disclosing the benefits of employing prodrugs, in particular ester prodrugs, i.e., “[e]sters are the most common prodrugs used, and it is estimated that approximately 49% of all marketed prodrugs are activated by enzymatic hydrolysis. Ester prodrugs are most often used to enhance the lipophilicity, and thus the passive membrane permeability, of water-soluble drugs by masking charged groups such as carboxylic acids and phosphates. The synthesis of an ester prodrug is often straightforward.” (page 256, right column). Rautio et al. go on to specifically teach examples of prodrugs that employ the functional group pivaloyloxy-methyl-ester in methods of prodrug strategy (Table 1 at page 257).
Regarding the breadth of modification groups and strategies disclosed by Rautio et al., a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005)(reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention." The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.").
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As such, it would have been prima facie obvious to one skilled in the art before the effective filing date of the claimed invention to modify the parent drugs TDM 180935 taught by CN 11067775 A, with a pivaloyloxy-methyl-ester functional group on the imino moiety, in order to prepare a prodrug having improved physiochemical and pharmacological properties.
In response to Applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Previous Double Patenting Rejections
70. 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).
71. 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).
72. 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.
73. 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.
74. Claims 1, 4-7, 9 and 10 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of copending U.S. Patent Application No. 18/248,362 (reference application, now allowed but not yet patented) in view of Rautio et al., Nature Reviews (2008).
Applicant’s instant claims are described in detail, above.
75. Application No. 18/248,362 recites the following:
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76. As such, the genus of small molecule compounds recited in Application No. 18/248,362 fully embraces compound species of Applicant’s instant Formula I, specifically compounds wherein “R” is a 5 or 6 membered aryl or heteroaryl group that is optionally substituted; “R1”-“R3” are carbon, and “R4” is either carbon or nitrogen; which corresponds to a compound of instant Formula I wherein R1 is carbon or nitrogen; R2 is
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; and R3 is as defined in the claim (Claims 1-7 and 12). Application No. 18/248,362 recites that said compounds have the same activity as the instantly recited compounds, i.e., JAK kinase inhibitory activity (Claim 8), and recites methods of preventing or treating the same autoimmune diseases (Claims 9 and 10) and inflammatory skin diseases (Claims 9 and 11).
77. The claims of Application No. 18/248,362 differ from Applicant’s instantly recited compounds because they are “parent drugs,” i.e., the nitrogen (N) attached to the phenyl or pyridyl ring is substituted by the moiety
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and Hydrogen, rather than the recited pivaloylmethyl ester functional group:
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78. However, Application No. 18/248,362 recites a prodrug of the small molecule compounds of the invention in Claim 1.
79. And, Rautio et al. teach numerous advantages of utilizing prodrugs in the pharmaceutical arts: a well-established strategy to improve physiochemical, biopharmaceutical and/or pharmacokinetic properties of pharmacologically potent compounds, increasing the usefulness of the active agent, wherein prodrugs increase solubility, improve absorption and distribution for organ or tissue specificity, enhance stability, make drugs temporarily non-toxic, and improve drug targeting, for example (page 255, first three paragraphs). Rautio et al. teach that esters are the most common prodrugs used (page 256, right column, under “Esters as prodrugs of carboxyl, hydroxyl, and thiol functionalities”), and go on to disclose several parent drugs having pivaloylmethyl ester functional groups, which is the same functional group attached to Applicant’s instantly recited compound:
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. In Table 1, Rautio et al. teach that the same pivaloyloxy-methyl-ester functional group significantly improved the oral bioavailability of ampicillin and adefovir prodrugs as compared to their parent drugs (page 257).
80. Regarding oral administration recited in instant claims 9 and 10, Application No. 18/248,362 teaches oral administration, in particular wherein “the medication of the present disclosure can be prepared into different dosage forms according to different routes of administration…as a tablet, a capsule, a pill, a granule…,” (see paragraph [0060]). 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).
81. As such, it would have been prima facie obvious to one skilled in the art to modify the parent drugs recited in Application No. 18/248,362, with a pivaloyloxy-methyl-ester functional group on the phenyl/pyridyl -NH moiety, in order to prepare a prodrug having improved physiochemical and pharmacological properties for the treatment of autoimmune and/or inflammatory skin diseases. One of skill in the art would have been motivated to prepare the instantly claimed pivaloyloxymethyl ester prodrug of the small molecule compounds recited in Application No. 18/248,362, and would have had a reasonable expectation of successfully obtaining prodrugs having improved bioavailability, as well as their methods of use in the prevention or treatment the same autoimmune diseases and inflammatory skin diseases.
Thus, claims 1, 4-7, 9 and 10 remain prima facie obvious over claims 1-12 of Application No. 18/248,362.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
82. Applicant acknowledges the double patenting rejection over the claims of the '362
application and Rautio et al., and elects to address this ground of rejection upon notification that all other conditions for patentability have been met, and that the pending claims are otherwise in condition for allowance.
83. Claims 1, 4-7, 9 and 10 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8 and 11 of copending U.S. Patent Application No. 17/771,070 (reference application) in view of Rautio et al., Nature Reviews (2008).
Applicant’s instant claims are described in detail, above.
84. Application No. 17/771,070 recites the following:
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85. As such, the genus of small molecule compounds recited in Application No. 17/771,070 fully embraces compound species of Applicant’s instant Formula I, in particular, compounds wherein “X1” is hydrogen; “X2” is nitrogen; the “G” ring is phenyl or pyridyl, “R1” is amino Nitrogen substituted by
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; which corresponds to a compound of instant Formula I wherein R1 is carbon or nitrogen; R2 is
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; and R3 is as defined in the claim (Claims 1 and 8); and specifically the compound species recited in Claim 11. Application No. 17/771,070 recites that said compounds have the same activity as the instantly recited compounds, i.e., JAK kinase inhibitory activity (Claim 1).
86. The claims of Application No. 17/771,070 differ from Applicant’s instantly recited compounds because they are “parent drugs,” i.e., the nitrogen (N) attached to the phenyl or pyridyl ring is substituted by the moiety
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and Hydrogen, rather than the recited pivaloylmethyl ester functional group:
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87. However, Application 17/771,070 specifically recites a prodrug of the small molecule compounds of the invention in Claims 1 and 11.
88. And, Rautio et al. teach numerous advantages of utilizing prodrugs in the pharmaceutical arts: a well-established strategy to improve physiochemical, biopharmaceutical and/or pharmacokinetic properties of pharmacologically potent compounds, increasing the usefulness of the active agent, wherein prodrugs increase solubility, improve absorption and distribution for organ or tissue specificity, enhance stability, make drugs temporarily non-toxic, and improve drug targeting, for example (page 255, first three paragraphs). Rautio et al. teach that esters are the most common prodrugs used (page 256, right column, under “Esters as prodrugs of carboxyl, hydroxyl, and thiol functionalities”), and go on to disclose several parent drugs having pivaloylmethyl ester functional groups, which is the same functional group attached to Applicant’s instantly recited compound:
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. In Table 1, Rautio et al. teach that the same pivaloyloxy-methyl-ester functional group significantly improved the oral bioavailability of ampicillin and adefovir prodrugs as compared to their parent drugs (page 257).
89. Regarding the use recited in instant claims 6-8, the conflicting claims may recite compounds having JAK inhibitory activity, where the rejected claims cover the use for preventing/ treating autoimmune diseases and inflammatory skin diseases. However, the specification of Application 17/771,070 discloses the utility of the recited compounds as JAK inhibitors as covered by the instant methods of using the compounds, i.e., “
“The present invention is intended to develop an optimal JAK kinase inhibitor with high potency and selectivity, especially a Tyk2 inhibitor and/or a JAK1 inhibitor, and/or a dual inhibitor for JAK1/Tyk2 or Tyk2/JAK1 and/or Tyk2/Jak2, which is applicable to treatment of autoimmune diseases such as rheumatic arthritis, ulcerative colitis and inflammatory skin diseases, with indications such as eczema and psoriasis,” (paragraph [0005]). See Sun Pharmaceutical Industries, Ltd., v. Eli Lilly and Co. where the district court ruled that the claims of the ‘826 patent were invalid in light of the ‘614 patent which disclosed gemcitabine’s use in cancer treatment, but did not claim it. 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.
90. Regarding oral administration recited in instant claims 9 and 10, Application No. 17/771,070 teaches oral administration (see paragraphs [0067] and [0071). 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).
91. As such, it would have been prima facie obvious to one skilled in the art to modify the parent drugs recited in Application No. 17/771,070, with a pivaloyloxy-methyl-ester functional group on the phenyl/pyridyl -NH moiety, in order to prepare a prodrug having improved physiochemical and pharmacological properties for the treatment of autoimmune and/or inflammatory skin diseases. One of skill in the art would have been motivated to prepare the instantly claimed pivaloyloxymethyl ester prodrug of the small molecule compounds recited in Application No. 18/248,362, and would have had a reasonable expectation of successfully obtaining prodrugs having improved bioavailability, as well as their methods of use in the prevention or treatment the same autoimmune diseases and inflammatory skin diseases.
Thus, claims 1, 4-7, 9 and 10 remain prima facie obvious over claims 1, 8 and 11 of copending Application No. 17/771,070.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
92. Applicant acknowledges the double patenting rejection over the claims of the '070 application and Rautio et al. and elects to address this ground of rejection upon notification that all other conditions for patentability have been met, and that the pending claims are otherwise in condition for allowance.
Conclusion
93. Claims 1, 2, 4-7, 9 and 10 are pending. Claims 1, 2, 4-7, 9 and 10 are rejected. No claim is presently allowable.
94. THIS ACTION IS MADE FINAL.
Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
95. 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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