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 Application
The Amendments, Remarks, and Declaration under 37 C.F.R. 1.132 filed on 12/29/25 are acknowledged.
Claim 13 was cancelled.
Claims 1-12 and 14-16 were amended.
Claims 1-12 and 14-16 are pending and are included in the prosecution.
Response to Amendments, Arguments, and Declaration
Applicant amended claim 1 to recite “A method of improving cardiac function of a patient with ischemic cardiomyopathy who undergoes coronary artery bypass surgery …” Previously, claim 1 was drawn to a pharmaceutical composition and not a method of treating. In light of this amendment, Applicant’s arguments (Pages 6-8, filed 12/29/25), and the Declaration under 37 C.F.R. 1.132 by inventor Shigeru Miyagawa (filed 12/29/25) regarding the following rejections have been fully considered and are persuasive.
Rejection of claims 1-3, 8, and 10-16 under 35 U.S.C. 102(a)(1) as being anticipated by Sawa et al. (US 2015/0231312 A1 – “Sawa”)
Rejection of claims 4-7 under 35 U.S.C. 103 as being unpatentable over Sawa
Rejection of claim 9 under 35 U.S.C. 103 as being unpatentable over Sawa in view of Rousou et al. (The Annals of Thoracic Surgery Vol 38, No. 4, October 1984, pp. 409-410 – “Rousou”)
Since the prior art references of record do not expressly teach the method now recited in the amended claims, the rejections listed above are withdrawn.
However, upon further consideration of the amended claims, a new ground(s) of rejection is made in view of Courtney et al. (US 2015/0152112 A1).
Since the new grounds of rejection were necessitated by Applicant’s amendment, this action is made FINAL.
Notice for all US Patent Applications filed on or after March 16, 2013
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 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.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 103
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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 1-8, 10-12, and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Courtney et al. (US 2015/0152112 A1 – “Courtney”) in view of Sawa et al. (US 2015/0231312 A1 – “Sawa”).
The claimed invention is a method of improving cardiac function of a patient with ischemic cardiomyopathy who undergoes coronary artery bypass surgery comprising administering a pharmaceutical composition, comprising:
a release formulation comprising at least poly(lactic-co-glycolic acid) (PLGA) and a prostaglandin I2 receptor agonist, the PLGA having an average molecular weight of 10000 to 30000; and
a release formulation comprising at least poly(lactic-co-glycolic acid) (PLGA) and a prostaglandin I2 receptor agonist, the PLGA having an average molecular weight of 40000 to 60000.
Courtney teaches a method for treating a patient suffering from or susceptible to a thromboembolic disease, which method comprises administering to said patient an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof ([1461]). The thromboembolic disease may be an arterial cardiovascular thromboembolic disorder ([1462]). The arterial cardiovascular thromboembolic disorder may be exemplified by ischemic cardiomyopathy and includes reocclusion and restenosis after coronary artery bypass surgery ([1463]). The compound may also be administered in combination with one or more further therapeutic agents, which include prostaglandin I2 agonists ([1466]).
Courtney does not expressly disclose parts (A) and (B) of the claimed pharmaceutical composition.
Sawa discloses an advanced heart failure treatment material comprising a pharmaceutical agent, an agent for holding the pharmaceutical agent, and a myocardial support device (Abstract, claims 1-27). The treatment material includes a sustained release preparation ([0095]-[0096], [0103]-[0104], claims 3-8, 11, 16, and 23). A prostaglandin I2 agonist is disclosed as an internal regeneration factor production inducing agent ([0026]-[0035] and claims 12-15) including Compound 1 which is (E)-[5-[2-[1-phenyl-1-(3-pyridyl)methylideneaminoxy]ethyl]-7,8-dihydronaphthalen-1-yloxy]acetic acid ([0035]), and which corresponds to ONO-1301 (recited in instant claim 11). Sawa also discloses that a microsphere (MS) formulation was produced by mixing example formulation 1 containing 25 mg of compound 1 and PLGA5-50 having a molecular weight of 50,000, and example formulation 2 containing 25 mg of compound 1 and PLGA5020 having a molecular weight of 20,000 at a ratio of 1:1; that the formulation is a sustained-release formulation that has a particle size of 31.4 μm and has sustained-release properties to release a drug over four weeks; that the formulation thus obtained has both of the sustained-release properties of example formulation 1 and the sustained-release properties of example formulation 2, and maintains high sustained-release properties over four weeks (Fig. 5) ([0038]-[0041], Examples 1-4). The formulation is prepared in the form of a sheet preparation of gelatin or the like, and fibrinogen or thrombin is added to the formulation; and that the formulation contains a surfactant such as polyoxyethylenealkylether phosphoric acid ester or a suspension of mannitol ([0174]), and includes the sheet preparation of Gelfoam by Pfizer Inc. ([0173]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of method for treating a patient suffering from or susceptible to a thromboembolic disease, wherein the thromboembolic disease is an arterial cardiovascular thromboembolic disorder, the arterial cardiovascular thromboembolic disorder is exemplified by ischemic cardiomyopathy and includes reocclusion and restenosis after coronary artery bypass surgery, and wherein the method includes administering one or more further therapeutic agents, which include prostaglandin I2 agonists, as taught by Courtney, in view of the heart failure treatment by administering a sustained release preparation including formulation 1 containing 25 mg of prostaglandin I2 agonist compound 1 and PLGA5-50 having a molecular weight of 50,000, and formulation 2 containing 25 mg of prostaglandin I2 agonist compound 1 and PLGA5020 having a molecular weight of 20,000 at a ratio of 1:1, as taught by Sawa, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because both the references teach the administration of prostaglandin I2 agonists in the treatment of cardiac diseases or conditions. It is obvious to combine prior art elements according to known methods to yield predictable results. Please see MPEP 2141(III)(A). One of ordinary skill in the art would have had a reasonable expectation of success in administering the composition containing the prostaglandin I2 agonist taught by Sawa in the method of treating ischemic cardiomyopathy in a patient who undergoes coronary bypass surgery of Courtney. One of ordinary skill in the art would have expected to achieve improved cardiac function in the patient because Courtney teaches that the conditions treated include reocclusion after coronary bypass surgery ([1463]).
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 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Regarding instant claim 1, the limitations of a method for improving cardiac function of a patient with ischemic cardiomyopathy who undergoes coronary bypass surgery would have been obvious over the method of treating a thromboembolic disease ([1461]), wherein the thromboembolic disease is an arterial cardiovascular thromboembolic disorder ([1462]), the arterial cardiovascular thromboembolic disorder is ischemic cardiomyopathy and includes reocclusion and restenosis after coronary artery bypass surgery ([1463]), as taught by Courtney, and the heart failure treatment material for the treatment of ischemic cardiomyopathy ([0047]), as taught by Sawa.
Regarding instant claims 1, 2, and 3 the limitations of (A) and (B), the ratio of A:B of 1:1, and the amount of (A) and (B), respectively, would have been obvious over the microsphere (MS) formulation produced by mixing example formulation 1 containing 25 mg of compound 1 and PLGA5-50 having a molecular weight of 50,000, and example formulation 2 containing 25 mg of compound 1 and PLGA5020 having a molecular weight of 20,000 at a ratio of 1:1 (Fig. 5) ([0038]-[0041], Examples 1-4 –[0184]-[0191]), wherein Compound 1 is (E)-[5-[2-[1-phenyl-1-(3-pyridyl)methylideneaminoxy]ethyl]-7,8-dihydronaphthalen-1-yloxy]acetic acid ([0035]), as taught by Sawa.
Regarding instant claims 4 and 5, the limitations of a patch liquid and a 5 w/v% mannitol aqueous solution comprising 0.2 w/v% of polysorbate, respectively, would have been obvious over the heart patch containing the sustained release preparation ([0175]-[0176]), the bioabsorbable base containing a suspending agent which is mannitol ([0174]), and the 0.2% (w/v) of Tween 80 (or Polysorbate 80) solution ([0188]). The recited concentration of the mannitol aqueous solution would have been an obvious variant over the use of mannitol as a suspending agent ([0174]), as taught by Sawa, absent evidence of criticality or unexpected results. One of ordinary skill in the art would have been motivated to do this because Sawa not only teaches that a heart attachment sheet of the sustained release pharmaceutical agent is prepared by adding and suspending the sustained release pharmaceutical agent containing the active substance(s) to/in a bioabsorbable base ([0173]) and that mannitol is used as a suspending agent ([0174]), but Sawa also teaches that polyoxyethylene alkyl ether phosphate esters are used as surfactants in the bioabsorbable base ([0174]), including the 0.2% (w/v) of Tween 80 (or Polysorbate 80) solution ([0188]). One of ordinary skill in the art would have found it obvious to use different concentrations of the suspending agent mannitol in solution along with different concentrations of surfactants including Tween 80 (or Polysorbate 80) based on the desired suspension of the active agents, the desired release of the active agents, and the required therapeutic efficacy. The recited concentration of the mannitol aqueous solution would have been an obvious variant over the use of mannitol as a suspending agent ([0174]), as taught by Sawa, absent evidence of criticality or unexpected results.
Regarding instant claims 6 and 7, the limitations of a gelatin patch and a porous sterile formulation comprising 10 g of gelatin per 1000 cm3, respectively, would have been obvious over the gelatin sheet that is impregnated with the MS preparation ([0045], [0051]-[0055], [0181], FIG. 2, Example 5 – [0203]-[0205], and claim 24), wherein the sheet preparation is Gelfoam, Gelfilm by Pfizer Inc. ([0054] and [0173]), as taught by Sawa. The instant specification discloses that “As the gelatin patch, it is preferable to use the commercial product YS-1402-Gelfoam (registered trademark, Pfizer Japan Inc.). YS-1402-Gelfoam is a spongy sheet agent obtained by blowing bubbles into Japanese Pharmacopoeia gelatin, and is a white porous sterile formulation containing 10 g of Japanese Pharmacopoeia gelatin per 1000 cm3” (Page 16, lines 34 to Page 17, line 4). Since Sawa teaches the same Gelfoam by Pfizer Inc. it is expected to have the same porous sterile formulation comprising 10 g of gelatin per 1000 cm3.
Regarding instant claim 8, the limitation of a plasma fraction formulation would have been obvious over the compound 1 MS suspended in a fibrinogen aqueous solution, and then admixed with Ca ions and liquid thrombin ([0054] and [0173]), as taught by Sawa.
Regarding instant claims 10 and 11, the limitations of the prostaglandin I2 receptor agonist would have been obvious over Compound 1 which is (E)-[5-[2-[1-phenyl-1-(3-pyridyl)methylideneaminoxy]ethyl]-7,8-dihydronaphthalen-1-yloxy]acetic acid ([0035]), as taught by Sawa.
Regarding instant claim 12, the limitation of a sheet patch would have been obvious over the gelatin sheet that is impregnated with the MS preparation ([0045], [0051]-[0055], [0181], FIG. 2, Example 5 – [0203]-[0205], and claim 24), as taught by Sawa.
Regarding instant claim 14, the limitation of the prostaglandin I2 receptor agonist released over 4 weeks after administration would have been obvious over the 4-weeks sustained release comprising the 1:1 (W/W) of the MS preparation of Example 1 and the MS preparation of Example 2 (Preparation Example 4 – [0190]-[0191]), as taught by Sawa.
Regarding instant claim 15, the limitation of a sustained-release formulation of microspheres (MS) would have been obvious over the 4-weeks sustained release comprising the 1:1 (W/W) of the MS preparation of Example 1 and the MS preparation of Example 2 (Preparation Example 4 – [0190]-[0191]), as taught by Sawa.
Regarding instant claim 16, the limitation of an average particle size of 3 to 300 µm would have been obvious over the MS preparation of Example 1 having a mean particle size of 35.4 µm ([0185]) and the MS preparation of Example 2 having a mean particle size of 32.6 µm ([0187]), as taught by Sawa. The particle sizes taught by the prior art lie within the claimed range and are rendered obvious based on MPEP 2144.05(I).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Courtney et al. (US 2015/0152112 A1 – “Courtney”) in view of Sawa et al. (US 2015/0231312 A1 – “Sawa”), as applied to claims 1-8, 10-12, and 14-16 above, in view of Rousou et al. (The Annals of Thoracic Surgery Vol 38, No. 4, October 1984, pp. 409-410 – “Rousou”).
Instant claim 9 is drawn to the method according to claim 8, wherein the plasma fraction formulation comprises a fibrinogen powder, an aprotinin solution, a thrombin powder, and a calcium chloride solution.
The teachings of Courtney and Sawa are discussed above.
Although Sawa teaches that compound 1 MS may be suspended in a fibrinogen aqueous solution, and then admixed with Ca ions and liquid thrombin ([0054] and [0173]), Sawa does not expressly teach an aprotinin solution as recited in instant claim 9.
Rousou teaches the use of fibrin glue in spray form for cardiac operations, wherein the fibrin glue consists of a mixture of fibrinogen, thrombin, calcium, and aprotinin (Page 409, Col. 1, 2nd ¶). The aprotinin is used as a stabilizing agent (Page 409, Col. 1, 2nd ¶), particularly as an antifibrinolytic stabilizing factor (Page 409, Col. 2, 2nd ¶). Calcium chloride is disclosed (Page 409, Col. 2, 1st ¶).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of method for treating a patient suffering from or susceptible to a thromboembolic disease, wherein the thromboembolic disease is an arterial cardiovascular thromboembolic disorder, the arterial cardiovascular thromboembolic disorder is exemplified by ischemic cardiomyopathy and includes reocclusion and restenosis after coronary artery bypass surgery, and wherein the method includes administering one or more further therapeutic agents, which include prostaglandin I2 agonists, as taught by Courtney, in view of the heart failure treatment by administering a sustained release preparation including formulation 1 containing 25 mg of prostaglandin I2 agonist compound 1 and PLGA5-50 having a molecular weight of 50,000, and formulation 2 containing 25 mg of prostaglandin I2 agonist compound 1 and PLGA5020 having a molecular weight of 20,000 at a ratio of 1:1, wherein compound 1 MS may be suspended in a fibrinogen aqueous solution, and then admixed with Ca ions and liquid thrombin, as taught by Sawa, in view of the fibrin glue used for cardiac operations, wherein the fibrin glue consists of a mixture of fibrinogen, thrombin, calcium, and aprotinin, as taught by Rousou, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because Rousou teaches that the aprotinin is used as a stabilizing agent (Page 409, Col. 1, 2nd ¶), particularly as an antifibrinolytic stabilizing factor (Page 409, Col. 2, 2nd ¶).
Regarding instant claim 9, the limitations of the plasma fraction formulation comprises a fibrinogen powder, an aprotinin solution, a thrombin powder, and a calcium chloride solution would have been obvious over compound 1 MS suspended in a fibrinogen aqueous solution, and then admixed with Ca ions and liquid thrombin ([0054] and [0173]), as taught by Sawa, in view of the fibrin glue in spray form for cardiac operations, wherein the fibrin glue consists of a mixture of fibrinogen, thrombin, calcium, and aprotinin (Page 409, Col. 1, 2nd ¶), and wherein the aprotinin is used as a stabilizing agent (Page 409, Col. 1, 2nd ¶), particularly as an antifibrinolytic stabilizing factor (Page 409, Col. 2, 2nd ¶), and the calcium is from calcium chloride (Page 409, Col. 2, 1st ¶),as taught by Rousou.
Conclusion
No claims are 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARADHANA SASAN whose telephone number is (571)272-9022. The examiner can normally be reached Monday to Friday from 6:30 am to 3:00 pm.
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, Robert A. Wax can be reached on 571-272-6023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ARADHANA SASAN/Primary Examiner, Art Unit 1615