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 .
Priority
Applicant has not filed an English language translation of foreign priority JP Application No. 2021-072843. It is suggested that a certified translation of every foreign benefit application or Patent Cooperation Treaty (PCT) application not filed in English be submitted. See 35 U.S.C. 119(b)(3) and 372(b)(3) and 37 CFR 1.55(g)(3)(i) and 41.154(b). A showing of priority that relies on a non-English language application is prima facie insufficient to overcome an intervening reference if no certified translation of the application is on file. See 37 CFR 41.154(b) and 41.202(e).
Information Disclosure Statement
The information disclosure statements (IDS) submitted on October 17, 2023 and April 9, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner, please refer to the signed copies of Applicant’s PTO-1449 forms, attached herewith.
Drawings
4. The drawings are objected to because:
Figures 1, the numbers and text on the x and y axes are blurry/ difficult to read.
Figure 2, the values printed within the bars are difficult to read, and the symbols identifying the data points on the graph have not been identified.
Figures 3-5, the numbers on the x-axis are difficult to read and the values printed within the LC-MS analysis are blurry/ difficult to read.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
5. Applicant is reminded of the proper content of an abstract of the disclosure.
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class. For processes, the type of reaction, reagents and process conditions should be stated, generally illustrated by a single example unless variations are necessary.
6. The abstract of the disclosure is objected to because the abstract does not set forth the method for growth promotion comprising administering the IPQ agent. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Rejections - 35 USC § 112
7. 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.
8. Claims 8-13 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.
9. Claim 8 recites a method “for growth promotion” in the preamble, however the claim is confusing because is it not clear what is intended by the limitation of "growth promotion," i.e., the growth of what/ which type of growth is specifically being promoted. For example, does this limitation reference the growth of a muscle, tissue, or cell? In the Specification, Applicant defines “growth promoter” as an agent having function of promoting growth of a living body, wherein the term “growth” refers to increase of body size, and a rate of the increase (see paragraph [0033]). However it is unclear whether Applicant intended growth to embrace increase in overall mass, or an increase in body length, for example.
10. Claims 9-13 are rejected as being dependent upon and including all of the limitations of claim 8.
In view of a broadest reasonable interpretation, the recitation of “A method of growth promotion” is construed to mean “A method of increasing body length.”
11. 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.
12. Claims 8-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventors, at the time the application was filed, had possession of the claimed invention.
13. As the Federal Circuit has stated: The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872, F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989).
14. The factors considered in the Written Description requirement are:
(1) level of skill and knowledge in the art,
(2) partial structure,
(3) physical and/or chemical properties,
(4) functional characteristics alone or coupled with a known or disclosed
correlation between structure and function, and
(5) the method of making the claimed invention.
15. Level of skill and knowledge in the art: The level of skill to practice the art of the instantly claimed invention is high and requires a variety of skills usually found in institutions and companies that employ highly trained and skilled scientists to carry out these tasks.
16. Partial structure; Physical and/or chemical properties; and Functional characteristics: Claim 8 is drawn to a method for “growth promotion,” the method comprising: administering to the subject an imidazopyrroloquinoline compound of Formula 1 and/or a salt thereof.
17. The instant specification teaches that the imidazopyrroloquinoline compound of Formula I (IPQ) is a reaction product of coenzyme pyrroloquinoline quinone (PQQ) and an amino acid, but does not have the same biological functions as PQQ. It is previously known that IPQ has an antioxidative effect (paragraphs [0005]-[0006]). The specification provides three working examples in daphnids, which Applicant alleges demonstrate that certain IPQ compounds (H-IPQ, Arg-IPQ, and Leu-IPQ) promote fat loss in the absence of calorie restriction as compared with the control, carnitine, or ECGC (pages 27-31 and Table 2), wherein the body fat reduction effect of H-IPQ, Arg-IPQ, and Leu-IPQ in the absence of physical calorie restriction actually corresponds to caloric restriction amounts of 45- 73% (pages 35-36 and Table 5); and demonstrate that Arg-IPQ and Leu-IPQ promote greater body length as compared to the control (page 32 and Table 3); and demonstrate that H-IPQ, Arg-IPQ, and Leu-IPQ each improve movement capability (pages 33-34 and Table 4).
18. There is no data or evidence provided of promoting any other kind of growth with the agent(s) of claim 1. And, it is noted that in Table 3, H-IPQ does not have any effect on body length. Arg-IPQ demonstrates a 0.21-0.27 mm increase in body length but only over Comparative Examples 1 and 2, and a decrease of 0.18 mm body length relative to Comparative Example 3. Leu-IPQ demonstrates a modest increase of 0.09-0.15 mm in body length over Comparative Examples 1 and 2, and a decrease in body length of 0.30 mm relative to Comparative Example 3. Therefore it can not be said that all three of the IPQ agents demonstrate a profound effect on body length; however, Arg-IPQ does appear to promote a noticeable increase in body length over Comparative Examples 1 and 2.
19. The term "growth promotion" covers a diverse array of processes embracing any type of growth in a living body, wherein the term “growth” can refer to increase of body size, or any muscle, tissue, and/or cell thereof, as well as the rate of the increase (see paragraph [0033]).
20. Applicants do not have possession of increasing all types and kinds of growth in the subject, as claimed, because the IPQ agents have only been tested on the body length of daphids, wherein only Arg-IPQ demonstrated a noticeable effect.
21. Despite the advanced training of those in the art, the pharmaceutical art is highly unpredictable. It is still not possible to predict the pharmacological activity or treatment efficacy of a compound based on the structure alone. Typically, in order to verify that a compound will be effective in a method or treating a disease, the compounds must be either tested directly in a patient or in a model that has been established as being predictive of efficacy. It is not predictable from the specification or from the prior art the agents of claim 1 promote all types and kinds of growth in any subject. The term ‘a subject,’ without limitation, includes any/all subject(s), including those who are healthy or with any type or kind of disease or disorder.
22. The level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. Ariad, 598 F.3d at 1351, 94 USPQ2d at 1172; Capon v. Eshhar, 418 F.3d 1349, 1357-58, 76 USPQ2d 1078, 1083-84 (Fed. Cir. 2005). The fields of biology and chemistry are considered “unpredictable” because the complexity and unpredictability of chemical and biological interactions can make it difficult to understand the exact properties of an invention. A person of ordinary skill in the art from the specification or from the prior art cannot predict the pharmacological effects of administration of the instant formulation in subjects in regards to prevention of pain. The pharmaceutical industry is the prototypical example of a highly unpredictable field. Pfizer v. Teva Pharm., 482 F.Supp.2d 390, 413 (D.N.J. 2007); 2 Chisum on Patents § 5.04.
22. Applicants have failed to provide guidance or data or evidence as to how the skilled artisan would be able to extrapolate from the disclosure to use the claimed invention. “A description of what a material does, rather than of what it is, usually does not suffice." Rochester, 358 F 3d at 923; Eli Lilly, 119 at 1568. Instead, the “disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described.” Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
23. The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521,222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.").
24. Accordingly, it is deemed that the specification fails to provide adequate written description for the claimed invention and does not reasonably convey to one skilled in the relevant art that the inventors had possession of the entire scope of the claimed invention.
Claim Rejections - 35 USC § 103
25. 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, 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.
26. The factual inquiries 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.
27. 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 as of the effective filing date of the claimed invention(s) 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 as of the effective filing date of the later invention 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.
28. Claims 7-23 are rejected under 35 U.S.C. 103 as being obvious over Urakami et al., JP10-45594 (English translation provided by Applicant, cited on IDS of October 17, 2023).
Claim 7 is directed to method for promoting lipid reduction, comprising administering to a subject imidazopyrroloquinoline of Formula I and/or a salt thereof:
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150
136
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, wherein R represents an amino acid residue, (selected from glycine, alanine, histidine, isoleucine, leucine, lysine, serine, threonine, tryptophan, tyrosine, or valine (more specifically glycine, leucine, or arginine claims 14-18)).
Claim 8 is directed to method for growth promotion, comprising administering to a subject imidazopyrroloquinoline of Formula I and/or a salt thereof:
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150
136
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, wherein R represents an amino acid residue, (selected from glycine, alanine, histidine, isoleucine, leucine, lysine, serine, threonine, tryptophan, tyrosine, or valine (more specifically glycine, leucine, or arginine (claims 9-13)).
In view of a broadest reasonable interpretation of claim 8, the recitation of “A method of growth promotion” is construed to mean “A method of increasing body length.”
29. Urakami et al. teach substituted IPQ derivatives as a class of compounds, according to Formula I:
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144
212
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(paragraph [0006])
wherein “R” is H, carbamoyl, phenyl, 4-methylphenyl, C1-4 alkyl, hydroxyl, carboxyl, methylmercapto, phenyl, 4-hydroxyphenyl, and C1-4 substituted with imidazoyl, amino, guanidino, methoxy or phosphate, and R1-R3 are selected from hydrogen, alkyl, allyl, propargyl, benzyl, phenyl, and alkoxycarbonylmethyl (paragraph [0007]). Urakami et al. teach that R can be an amino acid residue selected from histidine, lysine (paragraph [0013]), arginine, asparagine, O-methylserine (a residue of serine), O-phosphorylserine (a residue of serine), serine amide (a residue of serine) (see paragraph [0014]), and propionaldehyde (a residue of alanine) (paragraph [0015]).
30. In Examples 5 and 6, Urikami et al. teach the administration of 1-methylpropyl-IPQ, 2-methylthioethyl-IPQ, and benzyl-IPQ to mice to assess the inhibitory effects of said IPQ derivatives on liver injury (see paragraphs [0053] and [0054]).
31. Urikami et al. do not teach the administration of an IPQ-amino acid residue, however, it would have been obvious to one of skill in the art at the time of filing to modify Urikami et al. and substitute any of the small genus of amino acid residue-IPQ derivatives including histidine, lysine, arginine, asparagine, O-methylserine (a residue of serine), O-phosphorylserine (a residue of serine), serine amide (a residue of serine) and propionaldehyde (taught in paragraphs [0013]-[0015]) for 1-methylpropyl-IPQ, 2-methylthioethyl-IPQ, or benzyl-IPQ, for administration to mice to assess the inhibitory effect on liver injury, with a reasonable expectation of success. And, as noted by the court in In re Font, 675 F.2d 297 (CCPA 1982), an express suggestion to substitute one equivalent component (i.e., an equivalent IPQ derivative) for another is not necessary to render such substitution obvious. In the instant case, (1) the prior art element of Urikami et al. performs the function specified in the claim with only insubstantial differences (i.e., administration of an IPQ derivative); (2) the claimed component (i.e. an IPQ-amino acid derivative was known in the art); (3) a person of ordinary skill in the art would have recognized the interchangeability of the elements and could have substituted one known element for another; and (4) the results of the substitution would have been predictable.
32. Note that while Urakami et al. do not teach the inherent property of the instantly claimed compound to “promote lipid reduction” or “promote growth,” this result flows from the administration step itself. MPEP § 2112 (II) states "there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)." Furthermore, Integra Life Sciences I Ltd. v. Merck KGaA, 50 USPQ2d 1846 (DC SCalif, 1999) makes clear that a reference teaching a process may anticipate claims drawn to a method comprising the same process steps, despite the recitation of a different intended use in the preamble or the later discovery of a particular property of one of the starting materials or end products.
33. Applicant is additionally reminded that a preamble is generally not accorded any patentable weight where it merely recites the purpose of a process or the intended use of a structure, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps or structural limitations are able to stand alone. See In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976) and Kropa v. Robie, 187 F.2d 150, 152, 88 USPQ 478, 481 (CCPA 1951).
34. In the instant case, the patient population is not defined, the claim does not recite administration to a subject “in need thereof,” and the active step (i.e., administration of an imidazopyrroloquinoline derivative according to Formula I) taught by Urakami al. is identical to that recited by the instant claims.
See also Hoffer v. Microsoft Corp., 405 F.3d 1326 (Fed. Cir. 2005), noting that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited” (quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373 (Fed. Cir. 2003)). Although the Hoffer court was discussing the weight of a whereby clause, the reasoning applies equally to the weight of a preamble. In the instant case, as discussed above, the preamble (i.e., modulating PPARb activity in a cell) simply expresses the intended result of a process step positively recited, (i.e., administering an effective amount of methyl palmitate).
See also In re King, 801 F.2d 1324 (Fed. Cir. 1986), noting that “[u]nder principles of inherency, if a structure in the prior art necessarily functions in accordance with the limitations of a process or method claim of an application, the claim is anticipated. This is not to say that the discovery of a new use for an old structure based on unknown properties of the structure might not be patentable to the discoverer as a process... [but] if a previously patented device, in its normal and usual operation will perform the function which an appellant claims in a subsequent application for a process patent, then such application for process patent will be considered to have been anticipated by the former patented device.”
35. As such, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to substitute an IPQ-amino acid residue compound for 1-methylpropyl-IPQ, 2-methylthioethyl-IPQ, and benzyl-IPQ, for administration to a subject to assess its inhibitor effect on liver damage/ liver injury as guided by Urikami et al.. One of skill in the art would have been motivated to select an IPQ-amino acid residue derivative from the small genus taught by Urikami et al. in a method of administering an IPQ-derivative to assess for an inhibitory effect on liver injury, with a reasonable expectation of success.
As such, claims 7-18 are prima facie obvious.
Claims 19-22 are drawn to claim 7, wherein the administering is during exercise with an exercise intensity of 3 METs or more (claim 20), within 1 hour before starting the exercise (claim 21), or within 1 hour after ending the exercise (claim 22).
36. Dose regimen optimization is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize given the guidance of the prior art. As
the recited process is a well-known process, optimization of variables of said process such as timing of administration would be obvious to one skilled in the art. As such, one skilled in the art before the effective filing date of the claimed invention would have been motivated to administer the recited IPQ derivative as suggested by Urikami et al., and optimize the time of administration, with a reasonable expectation of success.
Thus, claims 19-22 are prima facie obvious.
Claim 23 is drafted in terms of the desired outcome of the administration of the IPQ derivative of claim 7:
“… wherein the method provides body fat metabolism promotion.”
37. The administration of an IPQ-amino acid residue to a subject is previously known in the art, as suggested by Urikami et al. If the prior art compound does in fact possess a particular benefit, even though the benefit is not recognized in the prior art, Applicant's recognition of the benefit is not in itself sufficient to distinguish the claimed composition from the prior art, In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1991). In this case, the ability of an IPQ derivative to promote “body fat metabolism” is considered a latent property of the administration of IPQ derivatives disclosed by Urikami et al. and the alleged unexpected result does not confer patentability. As such, one skilled in the art before the effective filing date of the claimed invention would have been motivated to administer the recited IPQ derivative as suggested by Urikami et al., with a reasonable expectation of success, wherein said administration promotes body fat metabolism.
As such, claim 23 is prima facie obvious.
Conclusion
38. Claims 7-23 are pending in the application, and all claims are presently rejected. No claim is allowed.
39. 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 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 L Clark can be reached at 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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/JANET L COPPINS/Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628