Detailed Action
The present office action is in response to the remarks filed 06 Jun 2025.
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
Claims 1-6 of the pending application have been examined on the merits. Claims 7-10 remain withdrawn. Acknowledgement is made of the amendments filed 06 Jun 2025.
Priority
Applicants identify the instant application, Serial #: 17/630,887 filed January 27, 2022, as a National Stage Entry of International Patent Application #: PCT/CN2020/105429, filed July 29, 2020, which claims priority from Foreign Application #: CN201910695723.0, filed July 30, 2019.
Response to Applicant Election
In the amendments filed 06 Jun 2025, applicant amended claims and limited the scope to compounds of Formula (I) that did not include the previously elected species (below) in the reply filed 23 Dec 2024:
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Because the instantly elected compound is no longer within the scope of the instant claims, examiner extended the Markush search to a compound in claim 4 (below) which reads on claims 1-6. This search retrieved prior art.
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Response to Applicant Arguments
Examiner acknowledges applicant amendments filed 06 Jun 2025.
The rejection of claims 1-6 over the written description requirement of 35 USC § 112(a) is rendered moot following applicant amendments.
The rejection of claim 6 over 35 USC § 112(b) is rendered moot following applicant amendments.
The rejection of claims 1-5 under 35 USC § 103 over US 2021/032253 further in view of Patani et al. (Chem Rev, 1996, 96:3147-3176) and Misra et al. (Bioorg Med Chem Lett, 2003, 13:2405-2408) are rendered moot following applicant amendments. New grounds of rejection for claims 1-5 necessitated by applicant amendments are found below.
The rejection of claims 1-6 under 35 USC § 103 over US 2021/032253 further in view of Patani et al. (Chem Rev, 1996, 96:3147-3176), Misra et al. (Bioorg Med Chem Lett, 2003, 13:2405-2408), Mentz et al. (Blood, 1996, 88:2172-2182), and Yasui et al. (J Leukoc Biol, 2000, 67:529-535) are rendered moot following applicant amendments. New grounds of rejection for claims 1-6 necessitated by applicant amendments are found below.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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) 1-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2021/0032253 (provided in IDS 01/27/22), hereinafter ‘253, further in view of Patani et al. (Chem Rev, 1996, 96:3147-3176; provided in the office action mailed 12 Mar 2025), hereinafter Patani, Barreiro et al. (Chem Rev, 2011, 111:5215-5246), hereinafter Barreiro, Mentz et al. (Blood, 1996, 88:2172-2182; provided in the office action mailed 12 Mar 2025), hereinafter Mentz, in light of Yasui et al. (J Leukoc Biol, 2000, 67:529-535; provided in the office action mailed 12 Mar 2025), hereinafter Yasui. ‘253 was published February 4, 2021 and claims Foreign Priority to Foreign Application #: CN201810118455.1 filed February 6, 2018 and so qualifies as art under 35 USC § 102(a)(2).
Examiner has expanded the Markush search to a species which reads on claims 1-5:
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Furthermore, the instant invention includes pharmaceutical compositions of the instantly elected invention and optionally a pharmaceutically acceptable carrier.
‘253 teaches compounds of Formula (III) (paragraph [0066]):
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Furthermore, ‘253 teaches Compound 4:
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which can be made from Formula (III) when R2 is H; L is CR4R5; R4 and R5 is H; R3 is alkyl; Rb is halogen; Y is a covalent bond; Ra is H; G is C; and s and p are 1. ‘253 teaches Compound 4 has binds to the adenosine A2α receptor with an IC50 value of 0.14 nM. ‘253 also teaches that R2 may be hydrogen, halogen, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, or heterocyclyl (paragraph [0017]) and that Ra may be attached anywhere on the phenyl substituent (paragraph [0066]). ‘253 further teaches the compounds of the disclosure or a tautomer, mesomere, racemate, enantiomer, or diastereomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof in a pharmaceutical composition with one or more pharmaceutically acceptable carriers, diluents, or excipients. However, ‘253 does not teach the instantly elected compound.
Patani teaches the substitution of hydrogen by fluorine is one of the more commonly employed monovalent isosteric replacements (pg. 3149, column 1). Patani also teaches that the ability of fluorine to replace hydrogen is an effective method of exploring the affinity of an agent to the target site by virtue of its greater electronegativity while other parameters such as steric size and lipophilicity are maintained (pg. 3150, column 1). Patani further teaches that methyl acts as a replacement for hydrogen according to Grimm’s Hydride Displacement law (pg. 3152, column 1).
Barreiro teaches that the methyl group is very important in the molecular recognition of organic compounds by bioreceptors and that it has stereoelectronic effects leading to diverse biological effects including selectivity, potency, and protection against enzyme metabolization (pg. 5215).
MPEP § 2144.09(II) teaches, “compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differeing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.”
By following the teachings of ‘253, Patani, and Barreiro, a person of ordinary skill in the art would modify Compound 4, as taught by ‘253, to modify the reference R2 group from H to methyl. The artisan would be motivated to have a reasonable expectation of success that performing this change would allow the artisan to explore potency and selectivity of Compound 4 for the adenosine A2α receptor. The artisan would further swap the ortho -F for a -H and swap for a meta position to facilitate a positional isomer which has a sufficiently close structural similarity the artisan would have a presumed expectation of the compounds having similar properties. The motivation to make the instantly claimed compounds derives from the expectation that structurally similar compounds would possess similar activity (i.e., they would be pharmacologically active adenosine A2α receptor inhibitors) with potential for better bioavailability and lower side effects. There would be a reasonable expectation of success in producing and using the instantly claimed compound in view of the compounds taught by ‘253.
Mentz teaches treatment of malignant B cells with theophylline, which induces intracellular accumulation of cAMP and chlorambucil (Abstract). Mentz teaches that theophylline and chlorambucil displayed a constant synergy between theophylline and chlorambucil at any concentration and time for inducing apoptosis in malignant B cells. Yasui, cited for evidence, teaches that theophylline is a weak adenosine A2A receptor antagonist and can induce apoptosis in neutrophils (Title; Abstract; and pg. 533, column 1).
Based on the teachings of ‘253, Patani, Barreiro, and Mentz, a person of ordinary skill in the art would substitute an adenosine A2α antagonist, such as theophylline, with another adenosine A2α receptor antagonist, such as the compound taught by ‘253, Patani, and Barreiro. The artisan would make this substitution in order to treat malignant B cells with a combination of chlorambucil, as taught by Mentz, with the expected result that the replacement adenosine A2A receptor antagonist would synergize with chlorambucil to induce apoptosis of malignant B cells.
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 foregoing 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 was 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
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached on (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.D.M./Examiner, Art Unit 1625
/Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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