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 .
Status of the Claims
Claims 4, 13-14, 16-23 and 26-35 are pending in the instant application and subject to examination herein.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. PCT/CN2022/074876, filed on 01/29/2022.
Claim Rejections - 35 USC § 112(b) – Withdrawn
The prior rejection of claim 23 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn in response to Applicant’s amendment of claim 23.
Claim Rejections - 35 USC § 112(d) – Necessitated by Amendment(s) and/or New Claims
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.
Claims 18, 21 and 30-35 are 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 4, from which all of claims 18, 21 and 30-35 depend, directly or indirectly, claims a genus of imidazopyridazine compounds of general formula (II), shown below, wherein ring A can be either a phenyl or thienyl ring, with additional substituent(s) and limitations.
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Claim 13, from which all of claims 18 and 30-35 depend, directly or indirectly, further limits the genus of claim 4 to a formula III-1, wherein ring A can only be trifluoromethylthienyl, with additional substituent(s) and limitations.
Claim 18 depends from claim 13, and purports to further limit claim 13 to a narrower genus III-2, wherein ring A is a trifluoromethylphenyl ring. Since the genus of claim 18 does not include the required trifluoromethylthienyl ring of formula III-1 bound to the imidazo ring of the core scaffold, the claim does not include all the limitations of claim 13, from which it depends.
Claims 30-35 all depend from claim 18, directly and indirectly, and each claims a genus of imidazopyridazine compounds bearing a trifluoromethylphenyl ring at the imidazo ring of the core scaffold; thus, none of these claims include all the limitations of claim 13, from which they all indirectly depend.
Claim 21 depends directly from claim 4, and further limits claim 4 to a Markush group of specific compounds, described by their structures, and claim 21 includes four specific compounds that do not comply with the limitations of claim 4, which requires that the “R3” group of formula (II) can only be azepan-4-yl or adamantyl whenever ring A is phenyl. The compounds shown below, numbered 15, 16, 26 and 30, all include an azaspiro[3.5]nonan-2-yl group as “R3”. Thus, claim 21 does not include all the limitations of claim 4.
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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.
Claim Rejections - 35 USC § 102 – Withdrawn
The prior rejection of claims 1-5 and 22-23 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Warner (WO 2016/161248 A1)1 is withdrawn in response to Applicant’s cancellation of claims 1-3 and 5 and amendment of claim 4.
The prior rejection of claims 1-5 under 35 U.S.C. 102(a)(1) as being anticipated by Pastor (Pastor, et al.; Bioorganic & Medicinal Chemistry Letters; v22, pp1591-1597; 2012) is withdrawn in response to Applicant’s cancellation of claims 1-3 and 5 and amendment of claim 4.
The prior rejection of claims 1-5, 9, 12 and 22 under 35 U.S.C. 102(a)(1) as being anticipated by Prien (CA2620534C) is withdrawn in response to Applicant’s cancellation of claims 1-3, 5, 9 and 12 and amendment of claims 4 and 22.
Claim Rejections - 35 USC § 103 – Withdrawn
The prior rejection of claims 1-4, 6-7, 13-14, 16 and 19-20 under 35 U.S.C. 103 as being unpatentable over Pastor (Pastor, et al.; Bioorganic & Medicinal Chemistry Letters; v22, pp1591-1597; 2012) in view of Brown (Brown; Bioisosteres in Medicinal Chemistry, Wiley-VCH, 2012) is withdrawn in response to Applicant’s cancellation of claims 1-3 and 6-7 and amendment of claims 4, 13-14 and 19-20.
Claim Rejections - 35 USC § 103 – Necessitated by Amendment(s)
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 18, 21 and 30-35 are unpatentable over Pastor in view of Brown.
Claims 18, 21 and 30-35 are rejected under 35 U.S.C. 103 as being unpatentable over Pastor (Pastor, et al.; Bioorganic & Medicinal Chemistry Letters; v22, pp1591-1597; 2012) in view of Brown (Brown; Bioisosteres in Medicinal Chemistry, Wiley-VCH, 2012).
The limitations of claims 18, 21 and 30-35 are discussed in the rejection above and hereby incorporated into the instant rejection.
Claim 18 depends from claim 13 and is drawn to a genus of imidazopyridazine compounds, designated as formula (III-2), shown below:
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Pastor teaches a compound that falls within bioisosteric equivalence of the genus of claim 18, identified as compound 8d2, as shown in the table below (page 1595, Table 4):
Claim Number(s) of Instant Application
Instant Application
Pastor
18
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wherein:
• R3 is 7-azaspiro[3.5]nonan-2-yl
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Pastor’s compound 8d differs from the scope of the genus of compounds of instant claim 18 because its core scaffold is triazolopyridine rather than imidazopyridazine. However, a person of ordinary skill in the art would have a reasonable expectation of success in making and using the imidazopyridazine-scaffold analogous compound for Pastor’s PIM kinase inhibitor compound 8d, because it was known in the art that imidazopyridazine and triazolopyridine are interchangeable scaffolds and their exchange should result in compounds of comparable biological activity, per the teachings of Pastor and Brown.
Pastor teaches a scaffold-hopping approach in the medicinal chemistry discovery of PIM kinase inhibitors, exploring a series of compounds across three molecular scaffolds: imidazopyridazines, triazolopyridazines and triazolopyridines, starting from the imidazopyridazine and triazolopyridazine scaffolds and developing the latter triazolopyridine scaffold as part of the study (page 1591). These scaffolds are shown in Pastor’s Figures 1 and 2, shown below:
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Figure 1: imidazopyridazine (left) and triazolopyridine (right) scaffolds
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Figure 2: triazolopyridine scaffolds
Pastor teaches that the motivation for this development was related to consideration of intellectual property: the imidazopyridazine and triazolopyridazine scaffolds “were already known as PIM inhibitors, and could not be considered as proprietary starting points for a hit to lead project” (page 1591). Thus Pastor does not advocate or demonstrate that the triazolopyridine scaffold is inherently superior to the imidazopyridazine and triazolopyridazine scaffolds, but rather that they are interchangeable in the search for PIM kinase inhibitors. Pastor also does not teach the scientific basis and standard practice of scaffold hopping as an approach in medicinal chemistry.
Brown teaches the principles and practice of bioisosteric replacements in medicinal chemistry. Brown teaches that “bioisosteric replacement of substituents, ring atoms, linkers, and other groups aims to generate chemical substitutes with related biological properties” (Preface). In the context of bioisosterism, Brown also teaches the principles and practice of scaffold hopping. Brown teaches that scaffold hopping “is a type of bioisosteric replacement where the fragment to be replaced is centrally placed within the active molecule, thus performing a key structural role. This fragment is replaced by a new chemical scaffold that maintains binding efficiency by preserving the existing orientations of the binding groups. The new scaffold should, roughly speaking, be of a similar size and shape as the original scaffold and, where appropriate, make similar interactions with the binding site. These new scaffolds may impart improved biological or physicochemical properties or avoid existing patent art” (page 91). Brown teaches that the practice of scaffold hopping is commonly performed using computer-based structural databases of known biomolecular targets, such as the Cambridge Structural Database (CSD), to model the interactions of known and proposed molecular structures with the target biomolecules (page 91). Brown provides an example of modeling scaffold replacements in inhibitor structure targeting serine protease factor Xa (pages 91-92, bridging paragraph, and Figure 5.9).
Applicant’s invention is unpatentable over the teaching of Pastor in view of the teaching of Brown, because a person of ordinary skill in the art, at the effective time of filing, would have a reasonable expectation of success in making and using PIM kinase inhibitors by making bioisosterically equivalent derivative of Pastor’s compound 8d having an imidazopyridazine scaffold in place of Pastor’s triazolopyridine scaffold, because Pastor teaches that these scaffolds are interchangeable for PIM kinase inhibitor compounds, and because Brown teaches the principles and practice of bioisosteric replacements and scaffold hopping.
Thus, the invention was prima facie obvious at the time of filing.
Claim 21 depends from claim 4, regarding a genus of imidizopyridazine compounds designated as formula (II), and claim 21 is drawn to a Markush group of specific compounds , including the specific compound, designated as compound “16”, that is the derivative of Pastor’s compound 8d bearing an imidazopyridazine scaffold in place of Pastor’s triazolopyridazine scaffold, as described in the rejection above:
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Claims 30-35 further limit claim 18, each to a narrower genus of compounds that is met by the rejection above.
Applicant’s invention is unpatentable over the teaching of Pastor in view of the teaching of Brown, because a person of ordinary skill in the art, at the effective time of filing, would have a reasonable expectation of success in making and using PIM kinase inhibitors by making bioisosterically equivalent derivative of Pastor’s compound 8d having an imidazopyridazine scaffold in place of Pastor’s triazolopyridine scaffold, because Pastor teaches that these scaffolds are interchangeable for PIM kinase inhibitor compounds, and because Brown teaches the principles and practice of bioisosteric replacements and scaffold hopping.
Thus, the invention was prima facie obvious at the time of filing.
Claims Free of the Prior Art
Claims 4, 13-14, 16-17, 18-20, 22-23 and 26-29 are allowed. Prior art does not teach or reasonably suggest, alone or in combination, a compound of formula (II) as claimed in claim 4, or a pharmaceutical composition comprising a compound of formula (II), or a method for treating and/or preventing a PIM-related disease, comprising administering a therapeutically effective amount of the compound, or the deuterated compound, the stereoisomer, or the pharmaceutically acceptable salt thereof according to claim 4 or a pharmaceutical composition comprising the compound, or the deuteride, the stereoisomer, or the pharmaceutically acceptable salt thereof according to claim 4 to a subject in need thereof.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to W. JUSTIN YOUNGBLOOD whose telephone number is (703)756-5979. The examiner can normally be reached on Monday-Thursday from 8am to 5pm. The examiner can also be reached on alternate Fridays.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S. Lundgren, can be reached at telephone number (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/W.J.Y./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 Cited in Applicant’s Information Disclosure Statement dated 10/27/2023.
2 N-{3-[3-(trifluoromethyl)phenyl]-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl}-7-azaspiro[3.5]nonan-2-amine
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