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 .
Priority
The instant application was received 21 August 2024; it is a national stage application of PCT/CN2023/077089, filed 20 February 2023, and claims foreign priority to CN202210157227.1, filed 21 February 2022. Acknowledgment is made of Applicant’s claim for foreign priority and certified copies of the priority documents have been received.
Status of the Claims
The listing of claims filed 21 August 2024 has been examined.
Claims 1-13, 15-19, 23-24, and 26 are pending.
Claims 3-13, 15-19, 23-24, and 26 are amended.
Claims 14, 20-22, and 25 are cancelled.
Claims 1-13, 15-19, 23-24, and 26 are examined on the merits.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 21 August 2024 is acknowledged and has been considered.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it contains a phrase which can be implied, specifically, “The present application relates to…” 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 13 is objected to because of the following informalities:
Claim 13 recites chemical structures and one, which is shown below, is blurry. Examiner requests a higher resolution image be provided.
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Appropriate correction is requested.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-13, 15-19, 23-24, and 26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Claim 1 recites, “A compound of formula (I), or a pharmaceutically acceptable salt, bioactive metabolite, solvate, hydrate, prodrug, racemate, enantiomer or stereoisomer thereof…” Particularly, the term “prodrug”, recited in claims 1, 4-13, 15, 17, and 23-24, invokes the 35 U.S.C. 112(a) rejection. Even a cursory calculation of the number of compounds embraced in the instant claims would result in thousands of compounds.
Level of Skill & Knowledge in the Art
The level of skill and knowledge in the art is high.
Partial Disclosure
Compounds of formula (I) have been disclosed and example compound species that would be within the general formula have been disclosed. However, as to the claimed prodrugs, no specific examples are given that would demonstrate possession or put the public in possession of all the claimed prodrugs of formula (I). It is generally accepted that prodrugs may vary by chemical formulae and may also differ in properties and the arrangement of atoms in the molecule.
Physical and/or Chemical Properties/Functional Characteristics
The compounds of formula (I), and prodrugs thereof, are compounds which are allegedly useful in methods for alleviating and/or treating a disease or disorder associated with the use of an antitumor agent in a subject (Claim 23) as well as treating and/or alleviating a JAK-mediated disease or disorder in a subject (Claim 24). Although the art recognizes generally accepted definitions, the terms are not explicitly defined by the Specification in such a way as to demonstrate that the inventor had possession of the prodrug of formula (I).
A review of the prior art identifies Najjar (Anas Najjar & Rafik Karaman (2019) Successes, failures, and future prospects of prodrugs and their clinical impact, Expert Opinion on Drug Discovery, 14:3, 199-220), which discloses successes and failures of prodrugs of known pharmaceuticals (p. 212, 3. Previous failed prodrugs). Najjar teaches hetacillin, an ester prodrug of ampicillin, which was withdrawn since it did not have a superior advantage when compared to ampicillin. In light of Najjar, it is unknown which of the prodrugs of compounds of Formula (I) claimed by Applicant is will be active or inactive. Further, one of ordinary skill in the art would not be able to predict which compounds, of the vast number that are claimed, will be active or inactive absent evidence. There is no structure/function correlation in the specification showing which prodrugs would or would not be active.
Since Applicant has not set forth compounds or substituents on formula (I) in the Specification which Applicant considers prodrugs, it is not clear what compounds fall under formula (I). Applicant has not described which prodrugs have the ability to antagonize JAK1, JAK2, JAK3, and/or TYK2 and which prodrugs lack said ability. Stated differently, there is no structure/function correlation and no representative number of specific examples of prodrugs that demonstrate which compounds retain activity. Further, one of ordinary skill in the art would not be able to predict the biological activity of the claimed prodrugs of formula (I).
Predictability of the Art
Medicinal chemistry is an experimental science with a low predictability level. Small changes in the structure of a compound can lead to large differences in their pharmacological activity. Regarding prodrugs, predicting if a certain claimed compound retains the activity and function of the original drug is filled with experimental uncertainty because prodrugs contain variation by chemical and physical properties of the molecules.
Method of Making the Claimed Invention
Although the Specification provides methods for making compounds of formula (I), no method for making all of the compounds, including the prodrugs, encompassed by the instant claims has been disclosed. Methods of synthesizing compounds are, in general, known to a person of ordinary skill; however, methods of making the myriad of compounds encompassed by the instant claims is beyond the skill of the artisan, particularly when certain elements, such as prodrugs are merely described partially.
As such, the instant specification and instant claims do not provide sufficient description such that one could anticipate what additional elements may be present in the prodrugs of formula (I) because the examples illustrated in the experimental section are limited to only compounds of formula (I).
Substantial and undue experimentation would be needed to practice Applicant’s invention because the specification lacks sufficient detail to show how to use the prodrugs of the instant invention. Further, there is no guarantee that all of the prodrugs embraced by the scope of the claims would be use in methods for treating JAK-mediated diseases/disorders.
Even with the undue burden of experimentation, there is no guarantee that one would obtain the product of a desired prodrugs of an instant compound of formula (I). Although some functional characteristics are disclosed or would be known to a person of ordinary skill in the art, in the absence of a disclosed structure, there can be no correlation between the function and structure of the claimed prodrugs in the instant application.
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad genus. It is unquestionable that the claim(s) are broad and generic with respect to all possible compounds encompassed by the claims. In other words, the possible structural variations are limitless to any prodrugs of the genus. In the instant case, however, the Specification does not disclose a sufficient variety of species to reflect this variance in the genus. The Specification does not provide sufficient descriptive support for the myriad of compounds embraced by the claims, such as prodrugs of formula (I).
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention. This rejection would be overcome by amending the claims to remove the term, “prodrug”.
Claims 1-12, 15-19, 23-24, and 26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Claim 1 recites, “G is a JAK inhibitor…” A “JAK inhibitor” could include compounds, presently, unrecognized as inhibiting JAK as well as undiscovered compounds which inhibit JAK. Accordingly, even a cursory calculation of the number of compounds embraced in the instant claims would result in thousands of compounds.
Level of Skill & Knowledge in the Art
The level of skill and knowledge in the art is high.
Partial Disclosure
Compounds of formula (I) have been disclosed and example compound species that would be within the general formula have been disclosed. The instant Specification provides a list of possible JAK inhibitors which can be G, such as Ruxolitinib and Tofactitinib (p. 4, Bottom Paragraph). However, disclosed exemplary compounds are limited to compounds wherein G is selected from known JAK inhibitors (p. 28-30; p. 52-57). The exemplary compounds provided are insufficient to demonstrate possession of all JAK inhibitors or put the public in possession of all the claimed compounds of formula (I) wherein G is any JAK inhibitor. Furthermore, the disclosed JAK inhibitors include compounds having distinct structures and, consequently, may also differ in properties.
Physical and/or Chemical Properties/Functional Characteristics
The compounds of formula (I) are compounds which are allegedly useful in methods for alleviating and/or treating a disease or disorder associated with the use of an antitumor agent in a subject (Claim 23) as well as treating and/or alleviating a JAK-mediated disease or disorder in a subject (Claim 24). Although the art recognizes generally accepted definitions, the terms are not explicitly defined by the Specification in such a way as to demonstrate that the inventor had possession of the prodrug of formula (I).
A review of the prior art identifies Jensen (WO 2008/128538 A1). Jensen discloses compounds which are inhibitors of protein tyrosine kinases of the Src family and useful for the treatment of inflammatory diseases or disorders involving protein tyrosine kinases of the Src kinase family (p. 1, Lines 5-8). One compound disclosed by Jensen is CAS RN: 854379-68-3 (p. 30, Line 15), shown below:
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Jensen indicates such compounds may, additionally, inhibit tyrosine kinases of the JAK family, such as JAK-2 (p. 28, Claim 4). No exemplary compound is instantly disclosed wherein G is a JAK inhibitor as described by Jensen. Furthermore, the instant Specification states, “The currently marketed and investigational JAK inhibitors primarily function by competing with the kinase domain for binding with ADP. As a result, JAK inhibitors generally suffer from low selectivity defect. Even inhibitors that are selective for a particular JAK subtype still face significant target-related side effects.” (p. 2, ¶ 1). Thus, in light of Jensen, it is unknown which compounds of formula (I) claimed be Applicant will be selective or non-selective. Further, one of ordinary skill in the art would not be able to predict which compounds, of the vast number that are claimed, will be active or inactive absent evidence.
There is no structure/function correlation and no representative number of specific examples of compounds of formula (I) wherein G is various JAK inhibitors to demonstrate which compounds retain activity. Further, one of ordinary skill in the art would not be able to predict the biological activity of the claimed compounds of formula (I) when G is different JAK inhibitors.
Predictability of the Art
Medicinal chemistry is an experimental science with a low predictability level. Small changes in the structure of a compound can lead to large differences in their pharmacological activity.
Method of Making the Claimed Invention
Although the Specification provides methods for making compounds of formula (I), exemplary synthesis strategies are limited to a relatively limited subset of all JAK inhibitors. Methods of synthesizing compounds are, in general, known to a person of ordinary skill; however, methods of making the myriad of compounds encompassed by the instant claims is beyond the skill of the artisan.
As such, the instant specification and instant claims do not provide sufficient description such that one could anticipate what additional JAK inhibitors may be present in the compounds of formula (I) because the examples illustrated in the experimental section are limited to only some JAK inhibitors.
Substantial and undue experimentation would be needed to practice Applicant’s invention because the specification lacks sufficient detail to show JAK inhibitors, both known and unknown, are compatible with the instant invention.
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad genus. It is unquestionable that the claim(s) are broad and generic with respect to all possible compounds encompassed by the claims. In the instant case, the Specification does not disclose a sufficient variety of species to reflect this variance in the genus. The Specification does not provide sufficient descriptive support for the myriad of compounds embraced by the claims, such as any JAK inhibitor.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention. This rejection would be overcome by amending the claims to encompass only JAK inhibitors which are supported by the disclosure.
Claims 23-24 and 26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because 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.
While the specification, in view of the prior art, reasonably provides enablement for the treatment of some diseases/disorders associated with the use of an antitumor agent, it does not reasonably provide enablement for the treatment of all diseases/disorders associated with the use of an antitumor agent or all JAK-mediated diseases/disorders.
MPEP § 2164.01(a) explains how enablement for the claimed invention can be analyzed:
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.” These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The Wands factors are analyzed with respect to the claimed elements in turn below.
The breadth of the claims and b) the nature of the invention. Claim 23 recites, “A method for preventing, alleviating and/or treating a disease or disorder associated with the use of an antitumor agent in a subject in need thereof…” Similarly, claim 24 recites, “A method for preventing, treating and/or alleviating a JAK-mediated disease or disorder in a subject in need thereof…” Accordingly, claims 23-24 are broad in scope as any disease/disorder associated with the use of an antitumor agent and any JAK-mediated disease/disorder are encompassed by the claim language. The instant Specification states, “…a disease or disorder associated with administration of the antitumor agent may be cause by the antitumor agent alone or by multiple treatment regimens including the antitumor agent… For example, the disease or disorder may comprise an epithelial disease or disorder.” (p. 35-36). Regarding JAK-mediated diseases/disorders, the instant Specification indicates said JAK-mediated disease/disorder may be selected from any one of many diseases and/or disorders (p. 40-45). Accordingly, the instant Specification provides broad and open-ended lists of diseases/disorders associated with the use of an antitumor agent and JAK-mediated diseases/disorders.
The state of the prior art. This can be ascertained by reviewing the Background of the Specification and relevant literature. Jensen (WO 2008/128538 A1) discloses compounds which are inhibitors of protein tyrosine kinases of the Src family and useful for the treatment of inflammatory diseases or disorders involving protein tyrosine kinases of the Src kinase family (p. 1, Lines 5-8). Said inhibitors may, additionally, inhibit tyrosine kinases of the JAK family, such as JAK-2 (p. 28, Claim 4). Additionally, Jensen suggests such compounds are useful, “…in the treatment of non-infectious inflammatory or autoimmune diseases or conditions in which protein tyrosine kinases of the Src family and/or the Jak-2… are significantly involved.” (p. 32, Claim 14).
The instant Specification states, “The currently marketed and investigational JAK inhibitors primarily function by competing with the kinase domain for binding with ADP. As a result, JAK inhibitors generally suffer from low selectivity defect. Even inhibitors that are selective for a particular JAK subtype still face significant target-related side effects.” (p. 2, ¶ 1).
The level of one of ordinary skill. This may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
The level of predictability in the art. Pharmacology is generally quite unpredictable. The more unpredictable an area is the more specific disclosure is necessary to satisfy the statutory requirement. MPEP § 2164.02(II) explains that a correlation between the claimed invention and the evidence provided in an application, along with a correlation between the evidence and the models recognized in the art, are required:
“Correlation” as used herein refers to the relationship between in vitro or in vivo animal model assays and a disclosed or a claimed method of use. An in vitro or in vivo animal model example in the specification, in effect, constitutes a “working example” if that example “correlates” with a disclosed or claimed method invention. If there is no correlation, then the examples do not constitute “working examples.” In this regard, the issue of “correlation” is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. In re Brana, 51 F.3d 1560, 1566, 34 USPQ2d 1436, 1441 (Fed. Cir. 1995) (reversing a USPTO decision based on finding that in vitro data did not support in vivo applications).
Further, treatments may be effective for some subjects and ineffective for other subjects. Thus, each candidate for pharmaceutical medicine must be evaluated on its own even when a nexus to an existing drug or class of drugs has been established.
The amount of direction provided by the inventor and g) the existence of working examples. The amount of guidance needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. The less predictable the nature of the invention, the more information needs to be explicitly stated in the Specification. See MPEP 2164.03.
The Specification provides exemplary synthesis methods (p. 50-52) as well as working examples demonstrating the in vivo efficacy of the claimed compounds in preventing and treating rashes caused by EGFR inhibitors using animal models (p. 62; p. 78). The instant Specification indicates JAK inhibitors are useful in inflammatory diseases (i.e., psoriasis and inflammatory bowel disease) and tumor diseases (i.e., myelofibrosis) (p. 1, ¶ 3) as well as cardiovascular disorders, Lyme disease, HIV-associated neuropathy, asthma, traumatic brain injury, dandruff, leukemia… (p. 9-15)
However, there is no detail nor experimental results, either in the application itself or in any other evidence of record, to support the notion that these compounds are useful for treating or preventing all of the extraordinarily large range of diseases or disorders within the scope of this claim. For example, there are no examples that in any way suggest that compounds of formula (I) are useful in preventing a traumatic brain injury. Additionally, the Specification does not provide any direction or teachings for how to treat or prevent, for example, various cancers in a subject.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure. The treatment or prevention of a disease or disorder associated with the use of an antitumor agent or a JAK-mediated disease or disorder would depend, at the very least, on the cause of said disease or disorder (e.g., chemical or physical) and the developmental stage of the subject (e.g., infant, adult, etc.). The prior art demonstrates that it is not possible for a single pharmaceutical product, or its analogs, to treat or prevent all diseases/disorders associated with the use of an antitumor agent or JAK-mediated diseases/disorders.
In order to practice the invention commensurate with the full scope of the claims, the skilled artisan would need to undertake experiments in order to determine (1) whether the compound is, in fact, clinically useful for the treatment or prevention of the claimed diseases or conditions; (2) the amount of compound that is to be administered; (3) the frequency of dosing and the manner in which the compound is to be administered; (4) the likely side effects and how they should be mitigated; and (5) the pharmaceutical formulation that is suitable for administration to a patient.
Scope of Enablement Conclusion
In view of the Wands factors discussed above, the disclosure of the instant application does not reasonably enable a PHOSITA to use the full scope of the claimed invention. While the state of the art does agree that JAK inhibitors have been effective in a wide range of immune diseases/disorders and inflammatory conditions, claims 23-24 and 26, as written, capture too broad a scope. Given the level of unpredictability in this technology area, and the relative lack of working examples or other specific guidance or teachings by Applicant, Examiner concludes that one skilled in the art would be burdened with undue experimentation when attempting to practice the full scope of the invention as claimed. Deleting the word “preventing” and limiting the diseases/disorders to those supported by the disclosure would overcome the rejection.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 11-12 and 26 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 26, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 12, the phrase “Modified Ruxolitinib Analog,” specifically the word “analog,” renders the claim indefinite because the word “analog” is undefined by the Specification and, accordingly, it is unclear how much structural variance is permitted by the word “analog.” For example, an “analog” could include compounds which lack significant structural similarity to the original compound. Thus, it is unclear which compounds are encompassed by the phrase “Modified Ruxolitinib Analog.”
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 4-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jensen (WO 2008/128538 A1).
Regarding claims 1 and 4-9, Jensen teaches the compound 2-Methyl-acrylic acid 2-[3-(4-{[2-(4-cyano-benzyloxycarbamoyl)-phenylamino]-methyl}-pyridin-2-yl)-ureido]-ethyl ester (p.30, Lines 15-16), shown below:
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In Jenson’s compound shown above, R1 is hydrogen, R is optionally substituted alkyl (i.e., ethyl having a methylene substitution), n is 2, and G is 2-[(2-Amino-pyridin-4-yl-methyl)-amino]-N-(4-cyano-benzyloxy)-benzamide (p. 29, Lines 27-28), shown below:
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Jensen suggests 2-[(2-Amino-pyridin-4-yl-methyl)-amino]-N-(4-cyano-benzyloxy)-benzamide is a JAX inhibitor (p. 28-29, Claims 4 and 11-13).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 4-9, 15-19, 23-24, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Jensen (WO 2008/128538 A1).
Regarding claims 1, 4-9, 15-19, 23-24, and 26, Jensen teaches all of the claimed elements as stated above. Furthermore, Jensen claims, “A method of reducing the proinflammatory activity in cells of a protein tyrosine kinase of the JAK family of protein tyrosine kinases, the method comprising contacting a cell expressing at least one protein tyrosine kinase of the JAK family of protein tyrosine kinases… in an amount effective to inhibit the activity of said protein tyrosine kinase in said cell.” (p. 36, Claim 33). Furthermore, Jensen teaches such compounds can be used in preparing pharmaceutical compositions which may be used in, “…the prevention or treatment of a non-infections inflammatory autoimmune disease or condition…” (p. 40, Claim 44). Some diseases/conditions Jensen indicates said pharmaceutical composition may be used in treating are allergy, chronic inflammatory diseases like allergy, psoriatic arthritis, ulcerative colitis, diabetic neuropathy, and Addison’s disease (p. 40, Claims 45-47). Furthermore, Jensen demonstrates JAK inhibitor compounds can reduce skin inflammation (p. 26, Lines 5-16) and collagen-induced arthritis (p. 23, Lines 16-23).
Additionally, Jensen discloses compounds which are JAK inhibitors may be included in a pharmaceutical formulation suitable for topical administration (p. 16, Line 15) and states, “The formulations may conveniently be prepared by any of the methods well known in the art of pharmacy. … All methods include the step of brings the active ingredient into association with the carrier, which constitutes one or more accessory ingredients.” (p. 16, Lines 16-20). Furthermore, Jensen discloses compounds suitable for topical administration include liquid or semi-liquid preparations (i.e., lotions or gels) as well as oil-in-water or water-in-oil emulsions (i.e., creams or ointments) (p. 18, Lines 5-9).
Jensen does not explicitly teach an exemplary composition comprising the compound 2-Methyl-acrylic acid 2-[3-(4-{[2-(4-cyano-benzyloxycarbamoyl)-phenylamino]-methyl}-pyridin-2-yl)-ureido]-ethyl ester and comprising about 0.001%-40% w/w of an instantly claimed JAK inhibitor.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Jensen would have found it prima facie obvious to prepare a pharmaceutical composition comprising an instantly claimed compound of formula (I) for use in treating inflammatory conditions and/or autoimmune disease based on the teachings of Jensen because Jensen discloses the compound 2-Methyl-acrylic acid 2-[3-(4-{[2-(4-cyano-benzyloxycarbamoyl)-phenylamino]-methyl}-pyridin-2-yl)-ureido]-ethyl ester, which is a compound of formula (I), and suggests such compounds be incorporated into pharmaceutical compositions for topical administration comprising a carrier and used in treating various inflammatory and/or autoimmune conditions. Although Jensen is silent the specific percent concentration of compound which should be included in said composition, a skilled artisan would have been motivated to optimize the percent concentration to achieve the desired anti-inflammatory effect while minimizing the occurrence of any undesirable side effects (MPEP 2144.05(II)).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANNA L BAUER whose telephone number is (571)272-5752. The examiner can normally be reached 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, ADAM C MILLIGAN can be reached at (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/B.L.B./Examiner, Art Unit 1623
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
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