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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/15/2025 has been entered.
Election/Restrictions
Applicant’s election without traverse of Group (I) in the reply filed on 11/20/2024 is acknowledged.
Applicant’s election without traverse of compound of example 46,
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in the reply filed on 11/20/2024 is acknowledged and maintained.
Expansion of Election of Species Requirement
A reasonable and comprehensive search conducted by the Examiner determined that the prior art at the time of the present invention was such that it did not anticipate or render obvious the elected species
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. In light of this discovery, the search is expanded to compound of example 5
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. This compound reads on the claimed compound of the formula (I)
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wherein
A is unsubstituted heteroaryl (e.g., morpholino);
R is a carbocyclo (cyclobutyl);
W is C(O)NRa, Ra is hydrogen;
R1 and R2 are both hydrogen atoms;
n is 1;
L is hydrogen or
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, Rd is substituted aryl (methyl substituted phenyl). and
R3 is hydrogen or methyl and claimed compound of the formula (I), wherein A is a heteroaryl substituted with three substituents, R is an alkyl substituted with an alkoxy, W is C(O)NRa and Ra is Hydrogen, R1 and R2 are both hydrogen atoms, n is 1, L is hydrogen, R3 is an alkyl.
Priority
This application is a continuation of International Patent Application No. PCT/US2020/035160, filed May 29, 2020, which claims the benefit of priority to U.S. Provisional Patent Application No. 62/854,181, which was filed on May 29, 2019.
Claims status
Claims 1-3, 19-31, and 37-43 are pending. Claims 4-18 and 32-36 are canceled. Claims 2-3, 23- 25, 28-31, 37-40, and 43 are withdrawn. Claims 1, 19-22, 26-27, and 41-42 are examined in accordance to the elected and expanded species. The formula (II) of claim 2 does not further limit the compound of the formula (I) of claim 1 and is therefore withdrawn.
Compound of claim 1 Compound of claim 2
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Action Summary
Claim 26 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, is withdrawn in light of the claim amendment.
Claims 1 and 27 rejected under 35 U.S.C. 102(a)(1) as being anticipated by
Bennett et al (US2010/0093696 A1), are withdrawn in light of the claim amendment.
Claims 1, 19-22, 26-27, and 41-42 rejected under 35 U.S.C. 103 as being unpatentable over Bennett et al (US2010/0093696 A1) in view of Asif et al (Hindawi Publishing Corporation Journal of Applied Chemistry, Volume 2013, Article ID 247203, pages 1-7) and Zhu et al (The Pharmaceutical Society of Japan, Chem. Pharm. Bull. 60(8) 1037–1045 (2012)), are maintained, but revisited and modified in light of the claim amendment.
Claims 1, 19-22, 26-27, and 41-42 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,603,372B2, are withdrawn in light of the approved terminal disclaimer filed 11/17/2025.
New 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 1, 19-22, 26-27, and 41-42 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 claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. While Applicants are in possession of the claimed of the formula (I) wherein
A is substituted morpholino; n is 1 or 2; R is H, optionally substituted phenyl, optionally substituted pyrimidyl, optionally substituted pyridyl, optionally substituted cyclopentyl, optionally substituted cyclobutyl, optionally substituted isoxazole, optionally substituted imidazole, optionally substituted pyrazolyl, optionally substituted oxetane, optionally substituted azetidine, or C4-alkyl; W is S(O2), C(O), C(O)NRa and Ra is hydrogen or lower alkyl; (CH2), or a bond; L is hydrazine or R3 and L together from an optionally substituted pyrazolyl ring; R1 and R2 are hydrogen; and R3 is H, Applicants are not in possession of all of the compounds encompassed by the formula (I).
This is a written description rejection.
The claims recite a broad generic A, L, W, R1, RR, and R3 that define compounds of the formula (I).
M.P.E.P. #2163 states: “An applicant shows possession of the claimed invention 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….one must define a compound by ‘whatever characteristics sufficiently distinguish it’. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process”.
The claims encompass the genus defined by the formula (I), covering the range substituents R, R1, R2, R3, W, and A, including specific species enumerated in description-such as heteroaryl or aryl, alkyl groups listed-demonstrating the breadth of the claims genus while supported by the concrete embodiment disclosed.
Accordingly, there is insufficient written description encompassing every substituent of R, R1, R2, R3, W, and A because the relevant identifying characteristics of the genus such as structure or other physical and/or chemical characteristics of each compound of the formula (I) are not set forth in the specification as-filed, commensurate in scope with the claimed invention. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed” (see page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (see Vas-Cath at page 1116).
Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddles v. Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. The specification provides only provides compound species for the formula (I) wherein A is substituted morpholino; n is 1 or 2; R is H, optionally substituted phenyl, optionally substituted pyrimidyl, optionally substituted pyridyl, optionally substituted cyclopentyl, optionally substituted cyclobutyl, optionally substituted isoxazole, optionally substituted imidazole, optionally substituted pyrazolyl, optionally substituted oxetane, optionally substituted azetidine, or C4-alkyl; W is S(O2), C(O), C(O)NRa and Ra is hydrogen or lower alkyl; (CH2), or a bond; L is hydrazine or R3 and L together from an optionally substituted pyrazolyl ring; R1 and R2 are hydrogen; and R3 is H. The instant specification does not make it clear if other substituents of R, R1, R2, R3, W, and A would give rise to the claimed compound of the formula (I) species. Thus, the specification fails to describe sufficient disclosed route of administration and sufficient compound of the formula (I) that gives rise to the claimed comparison. The Court further elaborated those generic statements are not adequate written description of the genus because it does not distinguish the claimed genus from others, except by function.
Per the Enzo court’s example, (Enzo Biochem., Inc. v. Gen-Probe Inc., 63 USPQ2d 1609 (CA FC 2002) at 1616) of a description of an anti-inflammatory steroid, i.e., a steroid (a generic structural term) couched “in terms of its function of lessening inflammation of tissues” which, the court stated, “fails to distinguish any steroid from others having the same activity or function” and the expression “an antibiotic penicillin” fails to distinguish a particular penicillin molecule from others possessing the same activity and which therefore, fails to satisfy the written description requirement. Similarly, the claimed compound of the formula (I) except the elected compound and compound species of the formula (I) that are exemplified does not satisfy the written-description requirement. Applicant has not disclosed enough relevant, identifying characteristics, such as structure or other physical and/or chemical properties, sufficient to show possession of the claimed genus. Mere idea or function is insufficient for written description; isolation and characterization at a minimum are required. A description of what a material does, rather than what it is, usually does not suffice. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
M.P.E.P. 2163 II-A-3-a ii) states: “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i) (C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) (Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.)”.
In the instant case, Applicant discloses 91 exemplified species within the scope of the formula (I). However, the claim encompasses a broad range of substituents beyond these examples.
Given the broad scope of the compounds claimed that can satisfy the claimed preambles, applicant has not provided sufficient written description (only one example in the specification) that would allow the skilled artisan to recognize that applicant was in possession of the genus of single disclosed oral tablet dosage form, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus. Thus, Applicant was not in possession of the claimed genus. See University of California v. Eli Lilly and Co. 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997).
In summary, the written description does not convey the full scope. In other words, the skilled person cannot discern from the application as filed that the applicant was in possession of the entire scope of the claimed compound of formula (I) genus.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 26 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 26 recites any one of compounds of example Nos. 1-30, 36-42, and 46-91 that include structural features not encompassed by the definition of W in claim 1, and thus, it introduces subject matter that is not supported by the original of the broader claim 1. Please see compounds 36 and 39 as depicted below. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Compound 36 Compound 39
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New Rejection
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 non-obviousness.
Claims 1 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Bennett et al (US2010/0093696 A1) in view of Patani et al (Chem. Rev. 1996, 96, 3147-3176).
Bennett teaches a pharmaceutical composition comprising a compound of the formula (I)
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wherein X is a bond, R1 is C3-C12 heterocyclcyl, or a pharmaceutically acceptable salt thereof, and a pharmaceutical acceptable carrier as a medicament for the treatment of cancer. (See claims 1,15, and 16.) Moreover, Bennett teaches the heterocyclyl can be a morpholinyl ring. (See paragraph [0125].) Furthermore, Bennett teaches one of the preferred compounds is compound 42
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. (See page 40].)
Bennett does not teach claimed compound of the formula (I),
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wherein A is a heteroaryl substituted with three substituents, R is an alkyl substituted with an alkoxy, W is C(O)NRa and Ra is Hydrogen, R1 and R2 are both hydrogen atoms, n is 1, L is hydrogen, R3 is an alkyl.
Patani teaches the ability of a group of bioisosteres to elicit similar biological activity has been attributed to common physicochemical properties. In this review an attempt
has been made to quantitate, in specific instances, physicochemical effects such as electronegativity, steric size, and lipophilicity and to correlate these values to the observed biological activity. (See second paragraph of the left column of page 3148.) Moreover, Patani teaches the widespread application of the concept of isosterism to modify biological activity has given rise to the term bioisosterism. As initially defined by Friedman, bioisosteres were to include all atoms and molecules which fit the broadest definition for isosteres and have a similar type of biological activity, which may even be antagonistic. More recently this definition has been broadened by Burger as “Compounds or groups that possess near-equal molecular
shapes and volumes, approximately the same distribution of electrons, and which exhibit similar physical properties...”. The critical component for bioisosterism is that bioisosteres affect the same pharmacological target as agonists or antagonists and, thereby, have biological properties which are related to each other. (See fourth paragraph of the right column of page 3148.) Furthermore, Patani teaches the concept of isosteres came about in 1925 with Grimm’s Hydride Displacement Law (Fluorine and Hydroxyl, Amino, or Methyl Groups as
Replacements for Hydrogen). This law states: “Atoms anywhere up to four places in the periodic system before an inert gas change their properties by uniting with one to four hydrogen atoms, in such a manner that the resulting combinations behave like pseudoatoms, which are similar to elements in the groups one to four places respectively, to their right.” (See Section 4 of page 3152.)
It would have been prima facie obvious to one of ordinary skill in the art the time the invention was filed to modify compound 42 taught by Bennett by replacing any one of the hydrogen atoms including one of the hydrogen atoms on the amine group with a methyl group to give Applicant’s claimed compound. One would have been motivated to do so, because Patani teaches hydrogen and methyl groups are bioisosteres according to Grimm’s Hydride displacement law and bioisostere is defined as compounds or groups that possess near-equal molecular shapes and volumes, approximately the same distribution of electrons, and which exhibit similar physical properties. One would reasonably expect the modified compound to exhibit greater potency that its counterpart successfully.
Claims 1, 19-22, 26-27, and 41-42 are rejected under 35 U.S.C. 103 as being unpatentable over Bennett et al (US2010/0093696 A1) in view of Asif et al (Hindawi Publishing Corporation Journal of Applied Chemistry, Volume 2013, Article ID 247203, pages 1-7) and Zhu et al (The Pharmaceutical Society of Japan, Chem. Pharm. Bull. 60(8) 1037–1045 (2012)).
Bennett teaches a pharmaceutical composition comprising a compound of the formula (I)
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wherein X is a bond, R1 is C3-C12 heterocyclcyl, or a pharmaceutically acceptable salt thereof, and a pharmaceutical acceptable carrier as a medicament for the treatment of cancer. (See claims 1,15, and 16.) Moreover, Bennett teaches the heterocyclyl can be a morpholinyl ring. (See paragraph [0125].) Furthermore, Bennett teaches one of the preferred compounds is compound 42
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. (See page 40].)
Bennett does not teach claimed expanded compound of example 5.
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The difference between the prior art compound and the expanded compound is as follow:
Bennett compound 42 Claimed expanded compound 5
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Asif teaches Hydrazones (–NHN=CH group and R1R2C=NNH2) are present in many of the bioactive compounds with wide interest because of their diverse pharmacological applications and biological activities such as anticonvulsant, antidepressant, analgesic, anti-inflammatory, antiplatelet, antimicrobial, anticancer, antihypertensive, anthelmintic, antidiabetic, antiparasitic, and other anticipated activities. (See Abstract.) Moreover, Asif teaches hydrazine compounds that possess the 4-tolyl or 4-fluorophenyl moiety are more active than 4-bromoephenyl and 4-N, N-dimethyl aminophenyl. (See first paragraph of the right column of page 2.)
Zhu teaches the aryl methylene hydrazine moiety, an attractive active pharmacophore, has been successfully applied to the design of anticancer agents. It is noteworthy that aryl methylene hydrazinyl derivatives CID13401328) (Fig. 1) and benzylidene hydrazinyl derivatives reported by our research group showed potent antitumor activity against several cancer cell lines. (See last paragraph of the right column.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to select the compound 42 of Bennett and modify said compound by replacing the 4-bromo-2-chloro-5-methoxyphenyl with morpholinyl moiety and further replacing one of the hydrogen of the amino group of the 5,7-dihydro-6H-pyroolo[3,4-d] pyrimidine with N'-(3-methyl- benzylidene)-hydrazine to give Applicant’s claimed compound. One would have been motivated to do so, because not only Bennett teaches the morpholinyl and 4-bromo-2-chloro-5-methoxyphenyl are interchangeable and also because Zhu and Asif teach benzylidene hydrazine including N'-(3-methyl- benzylidene)-hydrazine is a moiety that can enhance anticancer activity. One would reasonably expect the modified compound to exhibit excellent anticancer activity that can be used to treat cancer successfully.
Applicant’s argument
Applicant argues with respect to the 103 rejection that claims 1-2, 19-22, 26-27, and 41-42 were also rejected under 35 U.S.C. § 103 as being unpatentable over Bennett in view of Asif and Zhu. As mentioned above, Bennett does not teach any compounds which include an L and R3 group which are not both hydrogens. Despite any other teachings, Asif and Zhu do not remedy this deficiency and do not provide any rationale or motivation for independently modifying either L or R3 in such a manner. Therefore, this rejection should also be withdrawn.
Examiner’s response
In response to applicant's argument is not persuasive because the modified and revisited rejection shifts focus on compound of example 5 claimed. The Examiner clearly provide the rational for modifying compound 42 of Bennett to arrive at the compound of example 5 claimed. In fact, both Asif and Zhu teach structural modifications-such as introducing a morpholinyl moiety and a hydrazine group-are known to enhance pharmacological properties Given Bennett’s compound 42 as a starting point, one would have found motivation in Asif’s teachings of hydrazone substitution and Zhu’s teaching of methylene hydrazinyl substitutions, and Bennett’s teaching of morpholinyl substitutions to arrive at the claimed compound. Thus, the combination of these teachings provides a clear rationale to modify Bennett’s structure in the manner claimed.
Terminal Disclaimer
The terminal disclaimer filed on 11/21/2025 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Conclusion
Claims 1, 19-22, 26-27, and 41-42 are not allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEAN P CORNET whose telephone number is (571)270-7669. The examiner can normally be reached Monday-Thursday from 7.00am-5.30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEAN P CORNET/Primary Examiner, Art Unit 1628