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 . 1
Status of Claims
Claims 1, 2 and 4-25 are pending, claims 1-2 and 4-11 are currently being examined, claims 14-25 are withdrawn. The examined claims are directed to elected Group I and below species with traverse.
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BL-670 or HKi6 2
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Disease/disorder: carotid atherosclerosis
It is noted that the species of compound searched has been expanded to include the sirtuin inhibitor, sirtinol. Further, the species of diseases examined has been expanded to include rheumatoid arthritis, gout, stroke, thrombosis and thrombotic thrombocytopenic purpura. See below.
Response to Arguments
Applicant’s amendments and canceling of claim 3, filed May 22 2025, with respect to the objection of claims 1, 3 and 10 have been fully considered and are persuasive. The objection of claims 1, 3 and 10 has been withdrawn.
Applicant’s amendments of claims to recite “sirtinol compound,” filed May 22 2025, with respect to the rejection of claims 1, 2 and 5-10 under 35 USC 112(b) have been fully considered and are persuasive. The rejection of claims 1, 2 and 5-10 has been withdrawn.
Applicant’s amendment of claim 1 and arguments, filed May 22, 2025 with respect to claims 1-4 and 6-11 rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. 2010/0137345A1 have been fully considered and are persuasive. The rejection of claims 1-4 and 6-11 has been withdrawn.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-2 and 4-11 are rejected under 35 U.S.C. 103 as being unpatentable over Prudent et al. Salicylaldehyde derivatives as new protein kinase CK2 inhibitors, Biochimica et Biophysica Acta 1780 (2008) 1412–1420 in view of Ampofo et al. Role of protein kinase CK2 in the dynamic interaction of platelets, leukocytes and endothelial cells during thrombus formation, Thrombosis Research 136 (2015) 996–1006. Prudent and Ampofo are cited on the PTO-892 form.
The method of claim 1 requires the core elements comprising:
administering an effective amount of sirtinol compound wherein the Sirtinol compound is not sirtinol, m-sirtinol, or p-sirtinol, and wherein the compound is a compound of Formula (A) or Formula (B), a salt thereof, or a salt hydrate thereof;
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to treat a disease by reducing inflammation, thrombosis and/or atherosclerosis in a subject in need.
Regarding claim 1 Prudent teaches, compound 5 of Table 1, within the scope of Formula A as follows as detailed below, with demonstrated CK2 activity at 1.5 µM, which fall under the scope of Applicant’s formula A.
Prudent Compound 5 at the R1 position teaches an aldehyde moiety, at a position equivalent to Formula A, where R2 is O; i is represented by a double bond and R3 is hydrogen. Compound 5 teaches its R2 is hydroxyl, where equivalent to Applicant’s formula A’s R1 group, R1 is hydroxyl. Compound 5 of Prudent teaches a hydrogen at a position equivalent to claimed Formula A’s R4 which is also a hydrogen. Compound 5 of Prudent teaches its R4 is hydrogen, at a position equivalent to claimed Formula A’s R5 group, which is also hydrogen. Prudent Compound 5 teaches R3 is hydrogen, where a hydrogen is found on a similar position of Formula A of claim 1.
While Prudent teaches compounds that fall within the scope of Formula A, claim 1 with CK2 inhibitory activity, it does not explicitly teach the treatment of thrombosis, atherosclerosis or inflammation as claimed. However, one of skill in the art would readily look to using CK2 inhibitors as taught by Prudent, in the treatment of diseases such as thrombosis (thrombus formation), atherosclerosis and inflammation, as these disease conditions are known to be treated via CK2 inhibition.
Ampofo 2015 teaches that thrombosis, in terms of thrombus formation, is a complex process characterized by the interaction of platelets, leukocytes and endothelial cells. See abstract.
Ampofo 2015 teaches its results indicate that CK2 is regulator of thrombus formation, affecting multiple interactions of platelets, leukocytes and endothelial cells. See Abstract. Ampofo 2015 teaches that these mechanisms crucially contribute states of various inflammation-related disease, including systemic lupus erythematosus. See page 1005, column 1; Conclusions. Ampofo 2015 concludes that treatment of mouse model subjects with photochemically induced thrombosis resulted in the significant reduction of complete vessel occlusion time with a particular CK2 inhibitor. Id. at 1005.
Prior to the filing of the present patent application, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) following the teachings of Prudent to modify with Ampofo 2015 in order to treat thrombosis and related inflammatory disease states with Prudent’s compounds having CK2 inhibitory activity.
The PHOSITA would have had a reasonable expectation of success because Prudent compounds have CK2 inhibitory activity, where Ampofo 2015 teaches the inhibition of CK2 to treat thrombosis and inflammatory conditions.
Regarding claim 2 and treating thrombosis, Ampofo 2015 concludes that treatment of mouse model subjects with photochemically induced thrombosis resulted in the significant reduction of complete vessel occlusion time with a particular CK2 inhibitor. See page 1005, column 1; Conclusions.
Regarding claim 3 and 11 and the limitations of compound BL-670 or HKi6
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, this compound is taught at Prudent Table 1 as compound 7,
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where R1 is CHO; R2 is OH; R3 is H and R4 is OMe. Also note Table 1 which discloses various substitutions of hydrogen, OH and OMe along with an aldehyde moiety providing a PHOSITA a rationale to substitute along the naphthalene core structure, for example compounds 5 and 6 also, at the same positions of claimed Formula A to arrive at the claimed compounds of claims 3 and 11.
Regarding claim 5, Table 1 of Prudent teaches its various compounds comprise an aldehyde moiety, see for example, compound 7.
Claim 6 recites the administration of sirtinol (derivatives) upregulates various activities, such as endothelial nitric oxide synthase; thrombomodulin 1; VEGF A; Thrombospondin; Monocyte chemoattractant protein; or CXC chemokine receptor type 4. Because the prior art teaches the administration of the same compound sirtinol, in the same effective amounts to the same patient in need, these upregulation activities are inherently present in the teachings of the art.
Claims 7-9 recite the limitations of upregulation of PI3K/Akt signaling; the occupation of a HEG1 binding pocket of KRIT1; and the induction of KLF2 or KLF4 expression. Because the prior art teaches the administration of the same compounds to the same patient in need, these limitations of claims 7-9 are inherently present in the teachings of the art.
Claim 10 is a method of improving laminar blood-flow in a subject comprising administration to the subject in need an effective amount of sirtinol compound (or salt) thereof that binds to KRIT1 FERM domain to inhibit binding with HEG1.
As discussed above, the art teaches the administration of the same sirtinol derivative to a subject in need, who would be in need of improved laminar flow of blood, such as a thrombosis patient. See above discussion of claim 1. Further, the binding of sirtinol to KRIT 1 FERM domain so as to inhibit binding with HEG 1 is inherently present as the prior art teaches administration of the same compound to the same patient in need, i.e. a thrombus patient. See above discussion of claim 1.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new grounds 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 WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 This application claims earliest priority to US Provisional 62/856,849 filed June 4 2019.
2 CAS Registry Number: 50493-59-9
2-Hydroxy-6-methoxy-1-naphthalenecarboxaldehyde (ACI)
2-Hydroxy-6-methoxy-1-naphthaldehyde
2-Hydroxy-6-methoxynaphthalene-1-carbaldehyde
2-Hydroxy-6-methoxynaphthalene-1-carboxaldehyde
6-Methoxy-2-hydroxy-1-naphthaldehyde