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 and Claims Status
Claims 1-15 were pending. In the amendment as filed on December 20, 2023, applicants have amended claims 10, 12, and 15; cancelled claims 1-7; and added new claims 16-20. Therefore, claims 8-20 are currently pending. Additionally, the present specification is amended in order “to add a cross reference to priority information section.”
Priority
The instant application is a national phase entry of International Application No. PCT/CN2022/100134, filed June 21, 2022, which claims the priority of PCT Patent Application No. PCT/CN2021/101322, filed June 21, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) filed on December 20, 2023 and May 19, 2025 are in compliance with the provisions of 37 CFR 1.97. All references have been considered except where marked with a strikethrough. A signed copy of Form 1449 is included with this Office Action.
Specification – Abstract
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because it contains an annotation in parenthesis reading “To be published with FIG. 2” that is not relevant to the proper contents of an abstract. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Specification – Disclosure
The disclosure is objected to because of the following informalities:
The disclosure has many run-on sentences that need to be corrected. For example, page 1, lines 16-17 read “The overall median survival time is 3.5 to 5.5 years, but the higher the risk level, the shorter the survival time, the median survival time of high-risk patients is about 2 years.” There should be separate sentences in this example so it properly reads “The overall median survival time is 3.5 to 5.5 years, but the higher the risk level, the shorter the survival time. The median survival time of high-risk patients is about 2 years.” On page 1, line 32, BMS is incorrectly written in the possessive form as “Bristol-Myers Squibb’s”. Furthermore, there is an additional space between the “Bristol-Myers Squibb’s (BMS)” and the period at the end of the sentence. Last, there are subject-verb agreement issues within the disclosure, as on page 1, line 35, which current reads “JAK inhibitors has shown” and should be correctly stated as “JAK inhibitors have shown”. The Examiner encourages the Applicant to check over the Specification for typographical errors, run-on sentences, subject-verb agreement problems, and any other possible minor errors.
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which applicant may become aware of in the specification.
Specification - Drawings
Acknowledgement is made of the drawings received on December 20, 2023. These drawings are acceptable.
Claim Objections
The claims are objected to because of the following minor informality:
Per MPEP 608.01(m), “while there is no set statutory form for claims, the present Office practice is to insist that each claim must be the object of a sentence starting with "I (or we) claim," "The invention claimed is" (or the equivalent)”. Presently, there is no such terminology.
Claims 8 is objected to because of the following informalities:
The claim is not consistent with proper Markush practice. The claims should be listed in the singular alternative format. As an example, the examiner suggests that claim 8 be rewritten to read, “…or a pharmaceutically acceptable salt, prodrug, solvate, or hydrate thereof” so as to be consistent with proper Markush practice. No new matter permitted. Appropriate action is required.
The claim should properly read “and administering a therapeutically effective amount of the medicament to a subject having myelofibrosis”. Please amend the claim to properly reflect the addition of the article “a” before “therapeutically effective amount” and “subject”.
In the limitation of R1 and R2, Applicant recites C5-10 heteroaryl twice, as in “…and the C5-10 heteroaryl and the C5-10 heteroaryl group has 1, 2, or 3 heteroatoms…” Examiner suggests deleting one of these repetitive phrases.
Claims 11 is objected to because of the following informalities:
The claim is not consistent with proper Markush practice. The claims should be listed in the singular alternative format. As an example, the examiner suggests that claim 11 be rewritten to read, “…and a pharmaceutically acceptable salt, prodrug, solvate, and hydrate thereof” so as to be consistent with proper Markush practice. No new matter permitted. Appropriate action is required.
In the limitation of X, Examiner suggests adding the word ‘wherein’, so that the claim reads “X is phenyl, wherein the phenyl is…”.
Claim 13 is objected to because of the following informality:
The claim is not consistent with proper Markush practice. The claims should be listed in the singular alternative format. As an example, the examiner suggests that claim 13 be rewritten to read, “the medicament also comprises an excipient” so as to be consistent with proper Markush practice. No new matter permitted. Appropriate action is required. Examiner suggests checking all claims to the extent necessary to determine that they are all written in the singular alternative format.
Claims 8, 10, 13-20 are objected to because of the following informality:
In the limitation of Y, it is unclear whether Y is connected to the core 1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one scaffold of formula I through the U point-of-attachment or through the point-of-attachment adjacent to the Z variable. In other words, two entirely different genera of compounds can be interpreted by claim 8, shown below:
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Examiner suggests amending the claims so that it is obvious where the Y variable is being attached to the core scaffold.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8-20 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.
In claim 8, the phrase “signs/symptoms associated with myelofibrosis” is ambiguous. Does the “/” indicate ‘and’, or does “/” indicate ‘or’ with regards to signs and symptoms? Or both?
Claim 8 recites “comprising the compound”. There is insufficient antecedent basis for this claim and it should properly read “comprising a compound”.
Claim 8 recites “the pharmaceutically acceptable salts”. There is insufficient antecedent basis for this claim and it should properly read “a pharmaceutically acceptable salt”.
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.
Written Description - Prodrug
Claims 8-20 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.
In the instant case, claims 8 and 11 are drawn to methods of administering a medicament comprising a compound of formula I or II and a “prodrug” thereof.
The compounds of formula I and formula II are structurally defined. However, the genus of a “prodrug” of formula (I and formula II are not fully structurally defined. It is unclear what is encompassed by the term “prodrug”. The specification only comments on a “prodrug” as follows (page 9, lines 13-19):
In the present invention, the term "prodrugs" refers to functional derivatives of the
compounds that are readily converted in vivo into the required compound. Thus, in the
methods for the treatment of the present invention, the term "administering" shall
encompass the treatment of the various disorders described with the compound specifically
disclosed or with a compound which may not be specifically disclosed, but which converts
to the specified compound in vivo after administration to the subject, for the treatment of
myelofibrosis and the symptoms/signs associated with myelofibrosis.
Prodrugs are derivatives or precursors of therapeutically active molecules which undergo bioconversion into their active form inside the body. See, for example, Walther et al (“Prodrugs in Medicinal Chemistry and Enzyme Prodrug Therapies.” Advanced Drug Delivery Reviews, vol. 118, Sept. 2017, pp. 65–77), which discusses prodrugs in medicinal chemistry and enzyme prodrug therapies. Prodrugs are molecules with little or no pharmacological activity on their own but have a built-in structural lability, which can liberate the active drug. Prodrugs are typically employed when, for example, the parent drug compound has poor aqueous solubility, poor absorption from the gastro-intestinal tract into the blood, poor rates of cell entry, or various other reasons (see Table 1 of Walther). Design strategy for a prodrug depends on the structural features of the parent drug molecule and availability of the appropriate chemical functionalities that can be used to mask pharmacodynamic activity of the drug through an attachment of a modifying group. Typically, an enzymatic process is relied upon for drug release.
In particular, Walther notes that esters are commonly used as prodrugs due to the ubiquity of esterases in the body and the abundance of hydroxyl and carboxylic acid functionalities in drug compounds (see pg. 67, “Esterases: a “universal tool for drug recovery”).
However, a person having ordinary skill would not readily envisage a prodrug of formula (I) or formula (II) having an ester, because there is no hydroxyl or carboxylic acid functionality in the compounds. Walther discloses other common prodrugs for bioconversion, such as phosphate prodrugs, nitrophenyl prodrugs, glycoside prodrugs, and others.
Applicant’s specification provides no examples of a “prodrug” of the compounds of formula I or II. Additionally, no disclosure is provided which would guide a person of ordinary skill toward a particular prodrug strategy or design for the compounds of formula I or II. The application does not provide any guidance for one skilled in the art on how the prodrug is converted to active compounds, by what mechanisms and at what site the prodrug will be activated, what in vivo enzymes are likely involved in cleaving the protected group, etc.
Methods of synthesizing compounds are, in general, known to the person of ordinary skill, however methods of making the myriad of compounds embraced by the instant claims is beyond the skill of the artisan, particularly when certain elements, such as a “prodrug”, are not described. 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 or II.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Dependent claims 9-10 and 12-20 do not resolve these issues, since these claims do not further limit or provide further structure of the “prodrug”. Accordingly, these claims are also rejected.
The rejection would be overcome by amending the claims to remove the term “prodrug”.
Scope of Enablement – Method of Treating with Compounds
Claims 8-9, 13-15, and 20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the following:
A method of treating myelofibrosis by providing a medicament comprising a compound, wherein the compound is selected from one or more of the compound of formula I (as recited in Claim 8)
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and the pharmaceutically acceptable salts, solvates and hydrates thereof, wherein:
R1, R2, and Q are as described in claim 10;
X is as described in claim 11;
Y is as described in claim 9;
R3 is C1-3 alkyl only
does not reasonably provide enablement for elements that are outside the scope of the enabling elements listed above. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention:
The nature of the invention relates to a method of treating myelofibrosis and the symptoms/signs associated with myelofibrosis, wherein the method comprising: providing a medicament comprising the compound, wherein the compound is selected from one or more of the compound of formula I and the pharmaceutically acceptable salts, prodrugs, solvates and hydrates thereof; and administering therapeutically effective amount of the medicament to subject having myelofibrosis.
Predictability of the art:
The hypothetical compounds in claim 1 would be unpredictable in terms of one skilled in the art being able to synthesize every possible compound claimed in instant claim 8. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Level of skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing and screening chemical compounds for particular activities such as a chemist, as well as experience in treating myelofibrosis in a subject, such as a medical doctor. Screening of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target, (i.e., receptor, enzyme, etc.) is well known.
The breadth of the claims:
The scope of the claims involves a method of treating myelofibrosis by providing and administering a medicament comprising compounds of formula I, shown below.
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Claim 8 is very broad in the number of variables and the options of substituents for each variable. There is an extremely large amount of hypothetical compounds included in claim 8.
The amount of direction provided, the presence or absence of working examples, and the quantity of experimentation necessary:
The specification only provides the synthesis of 1 compound and extends that reaction sequence to synthesize 15 additional compounds, for a total of 16 compounds, “using a method basically similar to that of Example 1” (page 19, line 15). In all of the compounds synthesized, R1 is CH3, R2 is H, X2 Z, W, and U are all N, Q is methylene or methylene substituted with CH3, and X is C6 aryl optionally substituted with halo, OCH3, and -SO2CH3. Additionally, examples are only provided where R3 are methyl. However, it would be assumed that the inventors are also enabled for R6 and R51 being ethyl or propyl, since these substituents are similar in size and reactivity. Compound 1 is used in various assays relevant to the myelofibrosis disease state (for example, human myoproliferative tumor cells HEL and SET-2 cells) and the compound is also administered humans, as shown in Example 5, page 28-31 in the Phase I study. While the Specification only shows assay data for Compound 1, it is presumed that all 16 would have similar results since they are all substituted benzene rings at variable X.
Synthesis methods are not taught in the specification to provide for the aforementioned variables to include all of the possible substituents listed in the claims. For example, there are no working examples of a compound of formula I wherein R2 is an -NH2 or a C5-10 heteroaryl, to name a few, or where Z, W, and U are all carbon, for instance. It would be expected that the varying ring sizes (e.g., where R1 is C10 heteroaryl) and heteroatoms in the rings (e.g., Z, W, U) would change the reactivity of the compounds, and therefore may require alternate synthesis methods. It would require one skilled in the art, such as a chemist, to perform thousands of reactions to determine which compounds of formula I can be prepared and would likely require synthesis methods other than those provided in the specification. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the instant claims do not comply with the enablement requirement of 35 U.S.C. 112(a), since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Claims 9, 13-15, and 20, which are dependent on claim 8, are also rejected for further requiring and/or reciting elements that are outside the scope of the enabling elements listed above.
Scope of Enablement - Prevention
Claims 8-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), first paragraph, because the specification, while being enabling for treatment, does not reasonably provide enablement for prevention. 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.
The following Wands factors have been considered if not explicitly discussed: (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.
Of particular note, the specification does not provide any definition of “treatment” or “treating”
so the Merriam- Webster dictionary definition 1, c of “treatment” was employed, which is defined as “the action or way of treating a patient or condition medically or surgically: management and care to prevent, cure, ameliorate, or slow progression of a medical condition.”
It is presumed “prevention” of the claimed condition would require a method of identifying those individuals who will develop the claimed condition before they exhibit symptoms. The current state of the art is that that full scope of diseases claimed within instant claims is not preventable or curable.
There is no evidence in the prior art that the instant composition would be usable as a preventative method, particularly for preventing diseases such as cancer. “Preventing” connotes an absolute absence of a condition which cannot reasonably be achieved with regard to infections, with few exceptions (such as vaccines to prevent the development of pathogen-borne illnesses). In addition, there is no definitive method by which to determine whether a patient will develop a particular condition and, thus, be in need of preventive therapy. This is distinguished from preventing the relapse or recurrence of certain conditions, in which case an objective basis may exist to identify patients at risk of disease or infection, and could reasonably be construed as treatment. Prior to the initial onset or occurrence, however, even if a patient can be identified as having known risk factors for a condition, there is no certainty that the patient would in fact develop the condition. Further, the failure of a disease, infection, or condition to develop cannot reliably be attributed to the claimed active agent(s). The non-development of a condition such as diseases such as cancer may be due to other factors such as lifestyle. In this sense, in the context of preventing a disease, the level of unpredictability is extremely high.
The factors to be considered in making an enablement rejection were summarized above. 1) Preventing diseases requires identifying those patients who will acquire the condition before the symptoms occur. This would require extensive and potentially open-ended clinical research on healthy subjects. 2) There is no working example of such a preventive procedure in man or animal in the specification. 4) The claims rejected are drawn to clinical pharmacology and are therefore physiological in nature. 5) The state of the art is that no general procedure is art-recognized for determining which patients generally will develop myelofibrosis before the fact. 6) The artisan using Applicants invention would be a Board Certified physician. Despite intensive efforts, pharmaceutical science has been unable to find a way of getting a compound to be effective for the prevention of myelofibrosis. Under such circumstances, it is proper for the PTO to require evidence that such an unprecedented feat has actually been accomplished, In re Ferens, 163 USPQ 609. No such evidence has been presented in this case. The failure of skilled scientists to achieve a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art, Genentech vs. Novo Nordisk, 42 USPQ2nd 1001, 1006. This establishes that it is not reasonable for any agent to be able to prevent myelofibrosis. 7) It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved" and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). 8) The claims broadly read on all patients, not just those undergoing therapy for the claimed conditions.
As claims 9-20 depend upon claim 8, they are also rejected.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 8-20 are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (US 2020/0385401 A1, published 12/10/2020, 102(a)1 date) in view of Senderowicz et al. (US 10,918,646 B1, published 02/06/2021, 102(a)1 date).
The instant application claims methods of treating myelofibrosis by providing and administering a medicament comprising compounds of formula I, shown below. A specific claimed species, and synthesis thereof, is Compound 1, taught in Example 1, on pages 17-19, also shown below:
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Xu teaches the exact species of compound 1 above on page 6, para 0101, labeled ‘Compound 19’. Xu additionally teaches other examples that read on the genus of instant formula I in reference Table 4 (page 13-16). Xu teaches that these compounds are useful as bromodemain inhibitors, especially BRD4 inhibitors, and their use in the treatment of bromodemain and extra-terminal domain (BET)-mediated diseases in Example 1, which shows the inhibitory activity of reference compounds against BRD4 (page 41-42, para 0321-0326) and Example 2, which shows pharmacokinetic data (page 42, para 0327). Further, Xu teaches oral administration of reference compounds with dose ranges between 1 mg to 100 mg (page 42, para 0328-0329). Xu does not teach a method of using these compounds to treat myelofibrosis.
Senderowicz teaches a method of treating myelofibrosis in a subject using reference compound 1 (CPI-0610) and teaches that reference compound 1 is an inhibitor of the BET family (col 5, lines 27-55; col 13, lines 61-67 and col 14 lines 1-22; and elsewhere).
Therefore, it would have been prima facie obvious at the time of the effective filing date for one of ordinary skill in the art to take the BET inhibitor compounds of Xu and apply it to methods of treating myelofibrosis described by Senderowicz with a reasonable expectation of success. One of ordinary skill would find motivation in that Senderowicz teaches BET inhibitors that treat myelofibrosis in human subjects.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
All claims are rejected.
No claims are allowed.
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/L.A.B./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624