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 .
DETAILED ACTION
This office action is in response to applicant’s reply filed on July 9, 2026
Status of Claims
Amendment of claim 1 and 14 and addition of claim 21 is acknowledged.
Claims 1-21 are currently pending and are the subject of this office action.
Claim 14 was withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 14, 2026.
Claims 1-13 and 15-21 are presently under examination.
Priority
The present application is a 371 of PCT/EP2022/050652 filed on 01/13/2022 and claims priority to foreign application EPO EP21305031.3 filed on 01/13/2021.
Rejections and/or Objections and Response to Arguments
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Rejections and/or Objections) or newly applied (New Rejections and/or Objections, Necessitated by Amendment or New Rejections and/or Objections not Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
Responses to Applicant’s arguments have been addressed immediately after the corresponding rejections, or in the section: Withdrawn Rejections and/or Objections, if the rejection was withdrawn.
Claim Rejections - 35 USC § 112 (Maintained Rejection)
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.
Claims 1-10, 13 and 15-20 stand 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 treating fibrotic disease comprising the administration of a compound of formula (1) as disclosed in Table 1 (Page 19) of the specification, it does not reasonably provide enablement for a method of treating fibrotic disease comprising the administration of a compound of formula (1), except for the ones disclosed in the above Table 1.
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. This is a scope of enablement rejection.
To be enabling, the specification of the patent application 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, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
the quantity of experimentation necessary,
the amount of direction or guidance provided,
the presence or absence of working examples,
the nature of the invention,
the state of the prior art,
the relative skill of those in the art,
the predictability of the art, and
the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention
Claims 1-10, 13 and 15-20 recite a method of treating a fibrotic disease comprising the administration of an effective amount of a compound of formula (1):
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to a subject in need thereof.
The relative skill of those in the art
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
3. The state and predictability of the art
A search of the prior art revealed that some of the compounds encompassed by formula (1) are known, however there is absolutely no data regarding their efficacy in treating fibrotic diseases.
It is also well known that the biological properties of organic small molecules highly depend on the core structure and the substituents of the core structure (also known as SAR: structure activity relationship). The more diverse the substituents are, the less likely is that they are going to show similar properties in a biological assay or similar effectiveness in treating a specific disease.
For example, it is known that “seemingly minor modifications of the molecule may result in a profound change in pharmacological response (increase, diminish, completely destroy, or alter the nature of the response). In pursuing analog design and synthesis, it must be recognized that the newly created analogs are different chemical entities from the lead compound. It is not possible to retain all and exactly the same solubility and solvent partition characteristics, chemical reactivity and stability, acid or base strength, and/or in vivo metabolism properties of the lead compound. Thus, although the new analog may demonstrate pharmacological similarity to the lead compound, it is not likely to be identical to, nor will its similarities and differences always be predictable.” (J. G. Cannon, Chapter Nineteen in Burger's Medicinal Chemistry and Drug Discovery, Fifth Edition, Volume I: Principles and Practice, Wiley-Interscience 1995, pp. 783-802).
In summary, the art of determining the in vitro/in vivo activity of a compound or set of compounds based on structural similarity to the known in vitro/in vivo activity of a known set of compounds with little structural diversity is highly unpredictable.
4. The breadth of the claims
The breadth of the claims is not commensurate in scope with the disclosure. The general formula (1):
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encompasses a very diverse and large number of substituents (R1, R2a, R3, R4, R5, Z and Y). For this reason, one of ordinary skill in the art may envision millions of possible compounds according to the above general formulas. However, the specification only discloses a limited set of compounds with a very narrow set of substituents (see specification Table 1, page 19). For example: Z and Y are always Oxygen, despite claiming that they can be Sulfur, Selenium, Nitrogen, etc. R1 is almost always phenyl, R2a is almost always -OH or -O-benzyl, R3 and R4 are almost always benzyl, and R5 is almost always -CH2-O-benzyl, despite the large diversity of substituents claimed, etc.
5. The amount of direction or guidance provided and the presence or
absence of working examples
MPEP 2164.03 states: “The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable arts, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971). However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because it is not obvious from the disclosure of one species, what other species will work”
The instant specification discloses a series of compounds within the scope of formula (1):
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The disclosed compounds share substantial structural similarities (Se specification page 19, Table 1), wherein Z and Y are always Oxygen, despite claiming that they can be Sulfur, Selenium, Nitrogen, etc. R1 is almost always phenyl, R2a is almost always hydroxy or o-benzyl, R3 and R4 are almost always benzyl, and R5 is almost always -CH2-O-benzyl, despite the large diversity of substituents claimed, etc.
Applicant did not provide a reasonable representative set of compounds encompassed by the above formula(1) to be effective in assays related to the treatment of fibrotic diseases, as such, and due to the diverse set of compounds encompassed by the above formula (1), Applicant did not provide enough data to show that there is a correlation between the biological/pharmacological activity observed for compounds listed in Table 1 of the specification and the biological/pharmacological activity of the diverse set of compounds encompassed by the claimed general formula(1).
As such, if there is no correlation, then the examples do not constitute working examples.
While it is understood that the absence of working examples should never be the sole reason for rejecting a claim as being broader than an enabling disclosure, the criticality of working examples in an unpredictable art, such as the in vitro and in vivo biological/pharmacological properties of the diverse set of compounds encompassed by formula (1), is required for practice of the claimed invention.
The specification provides no guidance that compounds of general formula (1) other than the ones disclosed on Page 19 (Table 1) of the specification, will have the same or similar efficacy in treating fibrotic diseases.
6. The quantity of experimentation necessary
As discussed above (see: 3. the state and predictability of the art), small changes in the substituents of the core structure can cause dramatic changes in biological properties. Based on this, and since applicant provides biological data for only a narrow set of compounds (see: 5. The amount of direction or guidance and the presence or absence of working examples above) it is expected that some, if not most of the
molecules with R1, R2a, R3, R4, R5, Z and Y substituents recited in the instant claims (except for those specifically listed in page 19 (Table 1) of the specification) will not possess the same or similar biological properties as the compounds tested as inferred by the claims and contemplated by the specification.
So, determining which and how to make a particular compound within the scope of formula (1):
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wherein the R1, R2a, R3, R4, R5, Z and Y substituents are different from the ones disclosed on page 19 (Table 1) of the specification, would require testing new synthetic pathways in order to make the millions of compounds encompassed by the above formula (1), and assaying for all these new compounds in order to determine if said compound/s possess asserted utility.
This is undue experimentation given the limited guidance and direction provided by Applicants.
7. Conclusion
Accordingly, the inventions of claims 1-10, 13 and 15-20 do not comply with the scope of enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
NOTE: To overcome this rejection, it is suggested that Applicant limits the compounds claimed to a more reasonable set that closely resembles the compounds disclosed in the specification on page 19 (Table 1).
Response to Applicant’s arguments related to the above rejection
Applicant's arguments have been fully considered but are not persuasive.
Examiner’s response:
The changes made by Applicant by limiting Y and Z to Oxygen do not suffice to overcome the above rejection.
R1 is always phenyl or substituted phenyl,
R2a is either -NH-benzyl, -NHCO-CH3, -OH or -OCO-Ph
R3 and R4 are always -OBn or combined are:
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R5 is always -OBn or
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,
despite the diversity of substituents claimed.
Claim Objections
Claims 11-12 and 21 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 mailing date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCOS L SZNAIDMAN whose telephone number is (571)270-3498. The examiner can normally be reached on Flexing M-F 7 AM-7 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, Amy L. Clark can be reached on 571 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARCOS L SZNAIDMAN/
Primary Examiner, Art Unit 1628
July 21, 2026.
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