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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 May 20, 2026 has been reviewed by the examiner and entered of record in the file.
Claims 1, 14, and 17 are amended.
Claims 1, 14 and 17 are under examination and are the subject of this office action.
Claim Objections
Claim 17 is objected to for missing the article “the” between the terms “of” and “following” in line 4 and in line 8, i.e., the claim recites “…comprising administering to a patient in need thereof a therapeutically effective amount of a compound of following formula…” [emphasis added].
Previous Claim Rejections - 35 USC § 112(b)
6. Claims 1, 14 and 17 were previously rejected 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.
7. Claims 1, 14, and 17 were previously rejected regarding the limitation "wherein the Epac1 protein is involved" in the preamble. Applicant amended claims 1, 14, and 17 to clarify that the cardiac disease “overexpresses the Epac1 protein,” therefore this aspect of the previous indefiniteness rejection is withdrawn.
8. It is noted that in the previous office action, it was recommended that the patient population should be incorporated into the preamble of the claims, i.e., the claims are presently drawn to a method of treating a disease but do not recite a method of treating/preventing a cardiac disease …[language omitted] in a patient in need thereof,”.
New Claim Rejections - 35 USC § 112(b)
9. 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.
10. Claims 1, 14 and 17 are rejected 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.
11. Claim 1 recites the limitation: "…administering to a patient in need thereof a therapeutically effective amount of a compound having the following formula…,” in lines 4-6, however there is insufficient antecedent basis for this limitation in the claim because the preamble of the claim recites a method for treating a cardiac disease rather than treating a subject/ patient. That is, the preamble fails to recite a method of treating a patient in need of treatment. It is recommended that the preamble be amended to recite: “[a] method of treating a cardiac disease selected from the group consisting of… in a patient in need thereof, wherein said cardiac disease overexpresses Epac protein, said method comprising administering to said patient: …”.
12. Claim 14 recites the limitation: "…administering to a patient in need thereof a therapeutically effective amount of a compound having the following formula…,” in lines 5-7, however there is insufficient antecedent basis for this limitation in the claim because the preamble of the claim recites a method for treating a cardiac disease rather than a subject/ patient. That is, the preamble fails to recite a method of treating a patient in need of treatment. It is recommended that the preamble be amended to recite: “[a] method of treating a cardiac disease selected from the group consisting of… in a patient in need thereof, wherein said cardiac disease overexpresses Epac protein, said method comprising administering to said patient:…”.
13. Claim 17 recites the limitation: "…administering to a patient in need thereof a therapeutically effective amount of a compound having the following formula" in lines 3-4, however there is insufficient antecedent basis for this limitation in the claim because the preamble of the claim recites a method for preventing a disease rather than a subject/patient. That is, the preamble fails to recite a method of preventing a disease in a patient need of treatment. It is recommended that the preamble be amended to recite: “[a] method of preventing cardiac reperfusion injury in a subject in need thereof, said method comprising administering to said patient…”.
New Claim Rejections - 35 USC § 112(a)
14. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
15. Claim 17 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of protecting against acute myocardial reperfusion injury (Example 5) in a patient in need thereof comprising administering the compound AM-001, does not reasonably provide enablement for prevention of any/ all diseases that are reperfusion injuries overexpression Epac protein, comprising administering said compound. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
16. As stated in MPEP §2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is ‘undue’.” The factors to be considered when determining whether a disclosure meet the enablement requirement of 35 U.S.C. §112, first paragraph, were described in In re Wands, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) as:
1. the nature of the invention;
2. the breadth of the claims;
3. the state of the prior art;
4. the relative skill of those in the art;
5. the predictability or unpredictability of the art;
6. the amount of direction or guidance presented [by the inventor];
7. the presence or absence of working examples; and
8. the quantity of experimentation necessary [to make and use the invention].
All of the Wands factors have been considered, with the most relevant factors discussed below.
17. The Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.” In the instant case, the claims are drawn to “a method of preventing a disease, wherein the disease is a reperfusion injury, wherein said disease overexpresses Epac protein, said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of following formula…”.
18. The Breadth of the Claims: as stated in MPEP 2164.08, “[t]he focus of the examination inquiry is whether everything within the scope of the claim is enabled” (emphasis added). Indeed, the Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright, 999 F.2d 1557 (Fed. Cir. 1993) (emphasis added). At the same time, however, it is also recognized that not everything necessary to practice the invention need be disclosed. Nor is it necessary that an Applicant test all the embodiments of his invention. In re Angstadt, 537 F.2d 498 (CCPA 1976) (emphasis added). In fact, as stated by the court in In re Buchner, 929 F.2d 660 (Fed. Cir. 1991), a patent need not teach, and preferably omits, what is well known in the art.
19. Accordingly, for purposes of enablement, the relevant concern is whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate in scope with the protection sought by the claims. Thus, while “a patent application is entitled to claim his invention generically” it is necessary that “he provide a disclosure sufficient to enable one skilled in the art to carry out the invention commensurate with the scope of his claims." Amgen, Inc, v. Chugai Pharmaceutical Co., Ltd. (Fed. Cir. 1991). As noted by the court in In re Fisher, 427 F.2d 833 (CCPA 1970), the scope of enablement must bear a “reasonable correlation” to the scope of the claims. See also Ak Steel Corp. v. Sollac, 344 F.3d 1234 (Fed. Cir. 2003) and In re Moore, 439 F.2d 1232 (CCPA 1971). As stated in MPEP 2164.08, resolution of this concern requires two stages of inquiry: “[t]he first is to determine how broad the claim is with respect to the disclosure. The entire claim must be considered. The second inquiry is to determine if one skilled in the art is enabled to make and use the entire scope of the claim without undue experimentation.”
20. The instant claims are drawn to a method of preventing a disease wherein the disease is a reperfusion injury, wherein said disease overexpresses Epac protein, comprising administering to a therapeutically effective amount of compound 1, or a pharmaceutical composition comprising comprising compound 1 to patient in need thereof. The scope of diseases to be prevented encompasses preventing a disease that is a reperfusion injury wherein the disease overexpresses Epac protein, which embraces a complex group that are often unpredictable and difficult to treat, let alone prevent.
19. Applicant demonstrates the protective effect of compound AM-001 against ischemia-reperfusion injury in the Specification at Example 5, wherein “acute injection of AM-001 is efficient to prevent myocardial reperfusion injury.” [emphasis added] (page 27, lines 24-26). Applicant does not demonstrate the protective/ prophylactic effect of compound AM-001 on any other type of reperfusion injury. As such, the claims are extremely broad with respect to the disclosure.
20. The state of the prior art and the predictability or lack thereof in the art: The diseases that the instant claimed compound are alleged to prevent consist of reperfusion injury wherein Epac is overexpressed. Presently available pharmacological treatments for reperfusion injury are often symptomatic, i.e., demonstrating promising results in treatment, but do not prevent or alter the course of or progression of the underlying disease because it cannot be prevented in all cases. The state of the art teaches that during the process of ischemia-reperfusion (I/R) injury, the signaling of EPAC isoforms EPAC1 and EPAC2 is overexpressed in a few organ systems including myocardial ischemia-reperfusion injury as well as retinal ischemia-reperfusion, wherein Epac2 is significantly increased (Xia et al., ARVO meeting abstract 2022).
21. Because of high level of unpredictability associated with “prevention” of the disease embraced by claim 17, a greater amount of evidentiary support is needed to fully satisfy the requirement of 35 U.S.C 112(a). Applicant provides an in vitro binding assay which demonstrates the protective effect of compound AM-001 against myocardial ischemia-reperfusion injury (prevents cardiomyocyte death) at Example 5 (pages 23-24 and 27). However, Applicant does not demonstrate the protective/ prophylactic effect of compound AM-001 on any other type of reperfusion injury, including reperfusion injury wherein Epac is overexpressed.
22. Applicant is additionally reminded that the patient population is still not defined, i.e., the claim does not recite administration for treating obesity in a subject “in need thereof.” In claim 17, the preamble recites a method of “preventing a disease,” however, the patient population is not defined as the claim does not recite prevention in a patient in need thereof, rather, the claim is drawn to “preventing a disease wherein said disease is a reperfusion injury… comprising administering to a patient in need thereof a therapeutically effective amount of….” That is, the preamble recites a method for preventing a disease, not a method of preventing cardiac reperfusion injury in a patient in need thereof. It is recommended that the claim be drafted as follows: “A method of preventing cardiac reperfusion injury in a patient in need thereof, said method comprising to said patient...[language omitted]”.
23. The level of the skill in the art: Practitioners in this art (medical clinicians, pharmacists and/or pharmaceutical chemists) would presumably be highly skilled in the art for treatment of persons with the claimed diseases.
24. The amount of direction or guidance present and the presence or absence of working examples: The data provided in the disclosure is insufficient evidence for methods of preventing the disease embraced by the claim, comprising administering compound AM-001. In fact, the only disclosure in the specification at all is found in in vitro binding assays demonstrating the inhibitory activity of compound AM-001 against Epac1 (Examples 2 and 3); the effect of AM-001 against Epac1 in cultured cells (Example 4); the protective effect of compound AM-001 against myocardial ischemia-reperfusion injury at Example 5 (pages 23-24 and 27). The Specification does not support the claims to prevention of any other type of reperfusion injury. And, “the selection of the examples… used as the disclosure to support a claim must be adequately representative of the area covered by it,” see In re Cavallito et al. (CCPA 1970) 429 F2d 452, 166 USPQ 552. Therefore the instant specification is lacking significant data to accommodate the alleged method of prevention.
25. The quantity of experimentation needed: After applying the Wands factors and analysis to the claims, in view of the Applicant’s entire disclosure, it is concluded that the practice of the invention as claimed would not be enabled by the written disclosure. Thus, the specification fails to provide sufficient support of the broad use of compound AM-001 for prevention of any other diseases that are ischemia-reperfusion injuries overexpressing Epac, as embraced by the claims. As a result, necessitating one of skill to perform an exhaustive search for which claimed disorders can be prevented by the claimed compound, in order to practice the claimed invention.
Conclusion
26. Claims 1, 14 and 17 are pending in the application, and all claims are rejected. No claim is presently allowed.
27. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached on Monday-Friday 8:30AM-5PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark, can be reached on 571-272-13101310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
