NOTICE OF ALLOWANCE
Status of Application
The instant application is being examined under the Patents Prosecution Highway (PPH) program.
The amendments and response filed 28 July 2026 are acknowledged and have been considered in their entireties. Claims 1-8 and 10-11 remain pending; Claims 8 and 11 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Thus, claims 1-7 and 10 remain subject to examination on the merits.
Withdrawal of Previous Objections/Rejections
The objection to claim 4 for a typographical error is withdrawn in view of the amendment to rectify.
The rejection of claim(s) 10 under 35 U.S.C. 102(a)(1) as being anticipated by Fei et al. (Ex. Opinion Thera. Targets, 2023 – cited on IDS) is withdrawn in view of the amendment to exclude papain as a derivative.
The rejection of claim(s) 1-4, 6 and 10 under 35 U.S.C. 102(a)(1) as being anticipated by or in the alternative as obvious over Kerényi et al. (Experimental and Molecular Pathology, 1988 – cited previously) is withdrawn in view of the amendment to exclude papain as a derivative.
Claim Interpretation
The term “chymopapain” is described in the specification on pp. 5-6. The specification states the following:
“Chymopapain refers to a group of sulfhydryl proteolytic enzymes.” (p. 5, last paragraph).
“…….the term also encompasses analogs or derivatives of chymopapain which retain the biological activity of the compound as described herein.” p. 6, 1st paragraph.
As such, the cysteine protease papain EC 3.4.22.2 is deemed an analog/derivative of the cysteine protease chymopapain EC 3.4.22.6 as it also is a sulfhydryl hydrolase having cysteine protease activity and thus retains the same sort of biological activity as chymopapain EC 3.4.22.6, including dissolving atherosclerotic plaques (see Fei et al. (Ex. Opinion Thera. Targets, 2023 – cited on IDS) and Kerényi et al. (Experimental and Molecular Pathology, 1988 – cited on previous PTO-892)).
While it is understood chymopapain EC 3.4.22.6 and papain EC 3.4.22.2 are two distinct enzymes (hence, their different EC numbers), the lack of description in the specification of exactly what defines a derivative of chymopapain results in the broad by reasonable interpretation above.
Maintained Rejection
Claim Rejections - 35 USC § 112(a)
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.
Claims 1-7 and 10 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention.
The MPEP in section 2163(I) states that the purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made/filed, of the specific subject matter claimed:
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonable conclude the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings.
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An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997)"
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed. Circ. 1997).
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." Furthermore, the courts have also held that possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
The claims are drawn to methods of dissolving an atherosclerotic plaque disposed on an inner surface of an artery in a subject in need thereof, the method comprising administering to said subject a therapeutically effective amount of chymopapain; or a method of treating, preventing or ameliorating atherosclerosis or complication thereof, by administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising chymopapain.
As noted above, the term “chymopapain” encompasses analogs and derivatives thereof. Also noting chymopapain as in EC 3.4.22.2 possesses several isozyme such as chymopapain-A, -B, -C. Thus, the genus of enzymes which can be utilized in the methods is extensive, even encompassing papain EC 3.4.22.6; and then derivatives thereof which can include those with insertions, deletions, substitutions etc., which must retain the biologically activity of the chymopapain has the function of dissolving atherosclerotic plaque in arteries; or prevents, treats or ameliorates atherosclerosis by administration to a subject in need thereof. However, while generally how the mechanism is known for how cysteine proteases work on protein substrates to cleave them, it is less clear how they interact with fatty substances, cholesterol, cellular waste products and calcium that make up plaques (See p. 8, last line to first paragraph p. 9 of instant specification). Thus, the genus of chymopapain derivatives and analogs is very large and variable, however, the structure function correlation required for the success of said derivatives is not clear from the specification or the prior art. The only chymopapains utilized in the examples in the specification are those naturally occurring/wild-type chymopapain(s) and the only derivatives used in the prior art are wild-type papain. This, however, is not sufficient to represent the large, variable and highly diverse group of chymopapains which are being claimed for use in the methods as claimed.
Applicant’s Remarks and Examiner Rebuttal:
Applicant’s traverse the rejection of record and state because isolated Chymopapain was used in the Examples and because the specification recites at top paragraph of page 6: "Moreover, the term also encompasses analogs or derivatives of chymopapain which retain the biological activity of the compound as described herein", that this provides a proper scope of protection of the invention (See Remarks, p. 4).
The Examiner has considered this argument but does not find it convincing because not a single derivative has been utilized or contemplated. While the prior art utilizes papain, which is considered a derivative of chymopapain (See Applicant’s own sequence alignment on pp. 5-6, showing 60.8% sequence identity; and see Claim interpretation above, especially that papain also has the same biological activity), these are the only two enzymes the are exemplified in either the specification or the prior art which provide support for the large and variable genus of chymopapain derivatives. While the structure and function of chymopapain as it pertains to protein substrates is very well known (e.g. the amino acids involved in the P and S sites for proteolytic activity), how cysteine proteases interact with fatty substances, cholesterol, cellular waste products, calcium and fibrin that make up plaques (See p. 8, last line to first paragraph p. 9 of instant specification) is far less known and understood. Given there is not a single derivative described, or even the extent of what encompasses a derivative bar the functional requirement (how that is achieved is the unknown), then the written description for chymotrypsin derivatives is lacking.
New Rejection
Claim Rejections - 35 USC § 112(a) – New Matter
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.
Claims 1-7 and 10 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention.
The claims have been amended as follows (claim 1; claim 10 is similar with the negative limitation): A method of dissolving an atherosclerotic plaque disposed on an inner surface of an artery in a subject in need thereof, the method comprising administering to said subject a therapeutically effective amount of isolated Chymopapain, or a derivative thereof that retains the biological ability of dissolving atherosclerotic plaque, and wherein said derivative is not papain.
The introduction of the negative limitation that the derivative is not papain is considered new matter. Papain is not recited in the application, thus, it cannot be considered a positively recited limitation which is negatively excluded in the claims (MPEP 2173.05(i)). While this is not the only way to provide support for a negative limitation, as noted in the MPEP 2173.05(i), last paragraph: “While silence will not generally suffice to support a negative claim limitation, there may be circumstances in which it can be established that a skilled artisan would understand a negative limitation to necessarily be present in a disclosure." Novartis Pharms. Corp. v. Accord Healthcare, Inc., 38 F.4th 1013, 2022 USPQ2d 569 (Fed. Cir. 2022) (quoting Ariad Pharm. Inc. v. Eli Lilly & Co., 589 F.3d 1336, 1351, 94 USPQ2d 1161, 1172).” Here, Applicant’s comment that because papain was not used in the Examples, this provides implicit support for its exclusion as a derivative (See Applicant’s Remarks, p. 4, regarding the written description rejection above). However, this does not account for derivatives. No derivatives of chymopapain were utilized so it cannot be established that there is support that papain as a derivative is implicitly excluded and has support. As such, this negative limitation (i.e. wherein said derivative is not papain) is considered new matter.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUZANNE M NOAKES whose telephone number is (571)272-2924. The examiner can normally be reached M-F (7-4).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 14 August 2026
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