DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1, 11, 25, 26, 38, 50, 52, 53, 56, 59, 61-63, 69, 77-80, 83, and 85 are pending. Claims 2-10, 12-24, 27-37, 39-49, 51, 54, 55, 57, 58, 60, 64-68, 70-76, 81, 82, 84, and 86 are cancelled.
Status of Priority
The present application is a 35 U.S.C. § 371 national stage patent application of International patent application PCT/US2021/021146, filed on March 05, 2021. This application also claims the benefits of Provisional U.S. Patent Application No. 62/985,679, filed on March 5, 2020.
Examiner’s note on novelty and nonobviousness
The closest prior art is:
Turkson et al. (Turkson) (WO 2012/018868 A1; published February 9, 2012).
Novelty:
Turkson teaches 2-hydroxy-4-(2-(phenylsulfonamido)acetamido)benzoic acid analogs:
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(herein, referred to as Turkson-formula-I)
as inhibitors of STAT proteins (abstract). The variables of Turkson-formula-I are defined in claim 1 of Turkson. The STAT inhibitors represented by Turkson-formula-I differ from those presently claimed in that all the compounds of Turkson have the amide N atom bonded to a 2-hydroxy-benzoic acid substituent instead of a heteroaryl, alkylene-squaryl, or heteroalkylene-squaryl group as presented in the instant case when defining R12.
Thus, the instant invention is considered novel.
Nonobviousness:
Both Turkson and the present invention disclose STAT inhibitors. Although a POSITA would have considered it obvious to further explore derivatives of the compounds disclosed in Turkson (such as the compounds of the present invention) as STAT inhibitors, Turkson does not teach nor suggest the following:
The amide N atom of a compound of Turkson-formula-I being bonded to a heteroaryl, alkylene-squaryl, or heteroalkylene-squaryl group instead of a 2-hydroxy-benzoic acid substituent and
The sulfonamide S atom being bonded to pentafluorophenyl AND the sulfonamide N atom being bonded to an alkyl-phenyl or an alkyl-pyridine group
to arrive at the instantly claimed compounds.
Thus, the instant invention is considered nonobvious.
Specification - Abstract
The abstract of the disclosure is objected to because it is not in compliance with 37 C.F.R. 1.72 (b). Specifically, the sheet presenting the abstract includes other parts of the application or other material. 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).
Applicant is reminded of the proper language and format for an abstract of the disclosure.
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.
An example of an amended abstract that does not include legal phraseology such as “said” is provided below:
The present invention relates to compounds represented by general formula I:
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with the variables defined herein. Also provided are pharmaceutical compositions comprising the compounds represented by general formula I. Both the compounds and the pharmaceutical compositions are useful for the inhibition of Signal Transducer and Activator of Transcription 5a and 5b (STAT5). Furthermore, the compounds and compositions of the present invention are useful for the treatment of cancer, such as, for example, breast cancer and pancreatic cancer.
Specification - Disclosure
The disclosure is objected to because of the following informalities:
On pg. 78, Example B2: NHF Cell Cytotoxicity Assay, it states: “IC50 values were determined using non-linear regression analysis, and are provided in TABLE 3 and TABLE 4 below.”
However, in Tables 3 and 4 as presented on pg. 80-84, there are only IC50 values reported that are related to the MV4-11 cell cytotoxicity assay as described in Example B1 on pg. 78. Examiner is unsure where to find the IC50 values related to the NHF cell cytotoxicity assay as described in Example B2.
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 errors of which applicant may become aware in the specification.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 11, 25, 26, 38, 50, 52, 53, 56, 59, 61-63, 69, 77, 78, and 85 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 enabling elements:
A compound represented by Formula (I):
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wherein
R1 is a substituted or unsubstituted phenyl, wherein the substituted phenyl is substituted with 1 to 2 substituents independently selected from C3-C6 cycloalkyl and C1-C6 alkyl
R2 is a substituted or unsubstituted phenyl or a substituted or unsubstituted pyridine, wherein the substituted phenyl or substituted pyridine is substituted with 1 to 3 substituents independently selected from a halogen and -CF3
R3 is pentafluorophenyl
R5 = R6 = R7 = R8 = R9 = R10 = H
R12 is:
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or
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wherein RQ is -OH, -O-(unsubstituted C1-C6alkyl) , -COOH, -NH2, mono-(unsubstituted C1-C6 alkyl)amino, or di-(unsubstituted C1-C6alkyl)amino and
Z = 0 or 1
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wherein RB is independently selected from H and C1-C3alkyl.
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n = p = q = 1
X = Oxygen atom.
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.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In evaluating the enablement question, several factors are to be considered. According to In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), these factors include:
1) The nature of the invention,
2) the state of the prior art,
3) the predictability or lack thereof in the art,
4) the amount of direction or guidance present,
5) the presence or absence of working examples,
6) the breadth of the claims, and
7) the quantity of experimentation needed, and
8) the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention
The nature of the invention claims compounds represented by general formula I:
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with the variables defined in the specification. Also provided are pharmaceutical compositions comprising the compounds represented by general formula I. Both the compounds and the pharmaceutical compositions are useful for the inhibition of Signal Transducer and Activator of Transcription 5a and 5b (STAT5). Furthermore, the compounds and compositions of the present invention are useful for the treatment of cancer, such as, for example, breast cancer and pancreatic cancer.
State of the prior art
See Examiner’s note on novelty and nonobviousness above.
The level of the skill in the art
The level of ordinary skill in the art is relatively high. A person of ordinary skill would typically have formal training in medicinal chemistry and/or organic synthesis and would be familiar with standard methods for evaluating the efficacy and safety of the present compounds in suitable biological assays.
The amount of direction or guidance present and quantity of experimentation necessary
The instant claims recite certain R groups of Formula (I) being substituted without providing any constraints on the substituents. For example, claim 1 states “R1 is substituted or unsubstituted phenyl” without providing any limitations on the substituents of the substituted phenyl. Therefore, the substituents can be any substituent of any size and made up of any atoms in any structural form. However, the instant specification only discloses 18 exemplified species of Formula (I) and provides synthetic procedures for the preparation of 9 out of those 18. In the absence of clear guidance, a person of ordinary skill in the art would require undue experimentation to make all the compounds of Formula (I) wherein the R groups can be substituted with any substituent.
Therefore, claims 1, 11, 25, 52, 53, 56, and 61 are rejected for not being fully enabled by the specification.
The presence or absence of working examples
The instant specification only provides working examples of 18 compounds: compounds 1001 through 1018 which comprise the enabling elements listed above. See pg. 42-45 of the specification for the compounds’ structures.
Therefore, claims 1, 11, 25, 26, 38, 50, 52, 53, 56, 59, 61-63, 69, and 77 are rejected for not being fully enabled by the specification.
The breadth of the claims
The claims are broad insofar as the instant claims recite a compound represented by Formula I wherein the compound can possess R groups that are substituted with any substituent.
Claims 78 and 85, which are dependent on claim 1, are also rejected for further requiring and/or reciting non-enabling elements as discussed above.
Claims 79, 80, and 83 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In evaluating the enablement question, several factors are to be considered. According to In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), these factors include:
1) The nature of the invention,
2) the state of the prior art,
3) the predictability or lack thereof in the art,
4) the amount of direction or guidance present,
5) the presence or absence of working examples,
6) the breadth of the claims, and
7) the quantity of experimentation needed, and
8) the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention
The nature of the invention as recited on pg. 8 of this office action is incorporated herein.
State of the prior art
See Examiner’s note on novelty and nonobviousness above.
The level of the skill in the art
The level of the skill in the art as recited on the bottom of pg. 8 and continued on the top of pg. 9 of this office action is incorporated herein.
The presence or absence of working examples
As the present compounds are novel and nonobvious, there is no prior art that disclose a method of modulating signal transducer and activator of transcription 5a and 5b (STAT5) proteins in a subject.
The instant specification also does not disclose the aforementioned method. It only reports the potency of the present STAT5 inhibitors as measured in an MV4-11 cytotoxicity assay (in vitro study). The instant specification does not disclose the potency of the present compounds in a subject. According to the instant specification, a “subject” is a vertebrate, such as a mammal, a fish, a bird, a reptile, or an amphibian (pg. 21, para. 0065). The term “subject” does not encompass cells.
The breadth of the claims
The claims are broad insofar as the instant claims recite a method of modulating STAT5 proteins in an unspecified subject in need thereof, comprising administering to a subject a therapeutically effective amount of a compound represented by Formula I wherein the compound can possess R groups that are substituted with any substituent.
For these above reasons, claims 79, 80, and 83 are rejected as they fail to comply with the enablement requirement.
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 1, 11, 25, 26, 38, 50, 52, 53, 56, 59, 61-63, 69, 77-80, 83, and 85 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1, 11, 25, 52, 53, 56, and 61 recite the term “substituted” in the context of a substituted R group without providing any limitations on the substituents of the substituted R group. According to the instant specification, “[t]he term ‘substituted,’ ‘substituent’ or the like… can refer to the replacement of one or more hydrogen radicals in a given structure with the radical of a specified substituent” (pg. 22, para. 0068). The specification then provides a non-limiting list of possible substituents and states that substituents may be further substituted. Therefore, merely stating that an R group is “substituted” without any constraints on the substituents is unclear because it encompasses an innumerable number of possible substituents for R. As such, the metes and bounds of the claimed invention cannot be ascertained and the claims are rendered vague and indefinite.
Claims 26, 38, 50, 59, 62, 63, 69, 77, 78, 79, 80, 83, and 85 (which are dependent on claim 1) are also rejected for further requiring and/or reciting the indefinite limitation of claim 1.
Claims 50 and 53 recite the term “isostere” which is indefinite because it would be unclear to one of ordinary skill in the art what compound scope would be covered by the term “isostere”. The specification only teaches: “As used herein, ‘carboxylic acid or an isostere thereof' refers to a carboxylic acid moiety, or a functional group or moiety that exhibits similar physical, biological and/or chemical properties as a carboxylic acid moiety” (pg. 47, para. 0121). This definition is unclear because it is unclear what would be considered “similar” properties as this is a relative term. Many examples are given but since the examples are not a definition it is unclear what the exact scope would be.
Claim 52, which is dependent on claim 50, is also rejected for further requiring and/or reciting the indefinite limitation of claim 50.
Claim 77 recites “The compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is selected from a compound of Table 1 or Table 2.” There is a lack of antecedent basis for the limitations, “Table 1” and “Table 2” as claim 1 (in which claim 77 is dependent on) does not disclose a Table 1 or Table 2.
Further, according to MPEP 2173.05(s):
“Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table ‘is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.’ Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).”
In the instant case, there are only 18 exemplified species of Formula (I). Therefore, instead of having claim 77 refer to Tables 1 or 2 of the instant specification, it would be clearer if Applicant pastes the 18 compounds into claim 77 instead.
Conclusion
No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
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/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624