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
1. This application is a 371 of PCT/BR2022/050303 08/02/2022. This application has PRO 63/228,472 08/02/2021
Claims 1-15 are pending.
Response to Restriction Election
2. Applicant’s election of group I and the species, compound 209, in the reply filed on May 11, 2026 is acknowledged. The election was made without traverse. According to applicants’ representative claims 1-5, 15 read on the elected species. As detailed in the following rejections, the generic claim encompassing the elected species was not found patentable. The search and examination was continued until prior art was found that anticipated or rendered obvious a non-elected species that falls within the scope of the generic Markush claim reading on the elected species. As per MPEP 803.02 II. C. “[T]he examiner must continue to search the species of the claim unless the claim has been found to be unpatentable over prior art.” The examiner “need not continue to search the claim if the claim is rejected over prior art”. [ibid. D.] Therefore, the search and examination is restricted to the claims reading on the elected species, and claims not reading on the elected species are held withdrawn.
Claim Rejections - 35 USC § 112
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.
3. Claims 1, 3-5, 15 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. Claim 1 states “A compound characterized in that it comprises”. MPEP § 2173.05(h), states “A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. If a Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group ‘comprising’ or ‘consisting essentially of’ the recited alternatives), the claim should generally be rejected under 35 U.S.C. 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim.”
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.
4. Claims 1, 3-5, 15 are 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 pharmaceutically acceptable salts, solvates, and hydrates, it does not reasonably provide enablement for isomers. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. 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.” These factors include, but are not limited to the following:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention
The claims embrace all possible isomers, constitutional, structural, stereoisomers, etc. No synthesis or information is given as to what these compounds are, therefore no synthesis can be undertaken. A key issue that can arise when determining whether the specification is enabling is whether the starting materials or apparatus necessary to make the invention are available. In the biotechnical area, this is often true when the product or process requires a particular strain of microorganism and when the microorganism is available only after extensive screening. The Court in In re Ghiron, 442 F.2d 985, 991, 169 USPQ 723, 727 (CCPA 1971), made clear that if the practice of a method requires a particular apparatus, the application must provide a sufficient disclosure of the apparatus if the apparatus is not readily available. The same can be said if certain chemicals are required to make a compound or practice a chemical process. In re Howarth, 654 F.2d 103, 105, 210 USPQ 689, 691 (CCPA 1981). According to the U.S. Court of Customs and Patent Appeals in In re Argoudelis , De Boer, Eble, and Herr 168 USPQ 99 at 101, "[o]rdinarily no problem in this regard arises since the method of preparing almost all starting materials can be set forth in writing if the materials are not already known and available to the workers in the art, and when this is done the specification is enabling to the public". In re Argoudelis , De Boer, Eble, and Herr 168 USPQ 99 at 104, "it is essential that there be no question that, at the time an application for patent is filed, (emphasis in original) the invention claimed therein is fully capable of being reduced to practice (i.e., that no technological problems, the resolution of which would require more than ordinary skill and reasonable time, remain in order to obtain an operative, useful embodiment)." That is not the situation here. There are no directions to prepare any isomers and the structure is not even disclosed. In re Howarth, 210 USPQ 689, (claimed derivatives of clavulanic acid not enabled by specification lacking information of how prepare the clavulanic acid or directions to reference materials containing such information), Ex parte Schwarze 151 USPQ 426 (where starting material is not known to art as of date of filing application, there must be included a description of preparation thereof to enable one skilled in this art to carry out applicant's invention), Ex parte Moersch 104 USPQ 122 (claims to process for the production of (1)-y1-p-nitrophenyl-2-dichloracetamindo-propane-1,3-diol not enabled because of failure to describe source or method of obtaining starting compound; although starting compound is identified by means of appropriate name and by structural formula). Even if the discussion were limited to isomers of alkyl groups several thousand possible chemical structure exist for this formula. At least for hydrocarbon alcohols the number of possible isomers has been calculated, Henry R. Henze and Charles M. Blair "THE NUMBER OF STRUCTURALLY ISOMERIC ALCOHOLS OF THE METHANOL SERIES" Journal of the American Chemical Society 1931, 3042. For a hydrocarbon alcohol series with 20 carbons (C20), 5,622,109 different isomers exist. The instant claims are more complicated because the claims are not just drawn to alcohols, but many generic groups. The factors outlined in In Re Wands mentioned above apply here, and in particular as per the MPEP 2164.01 (a): “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” It is very clear that one could not make/use this very broad invention that has no working examples in this unpredictable art without undue experimentation.
5. Claim 3 is 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 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. An objective standard for determining compliance with the written description requirement is, "does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an 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, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon "reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter." Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)). Whenever the issue arises, the fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). See M.P.E.P. § 2163.02. In this case, the skilled artisan would not have reasonably concluded at the time of the invention that applicant was in possession of the entire invention as claimed.
Claim 3 is drawn to compounds of claim 1 limited by ”characterized in that it is a selective inhibitor of the voltage-gated sodium channels Nav 1.7 and/or Nav 1.8”. They therefore seek to define a subset of claim 1 compounds by particular functional requirements. The specification, however, does not provide any specific correlation between a particular structural property and the claimed function. The ability of a compound to be “a selective inhibitor of the voltage-gated sodium channels Nav 1.7 and/or Nav 1.8” is highly dependent on a number of factors. According to Li “A structural atlas of druggable sites on Nav channels” CHANNELS 2024, VOL. 18, NO. 1, 1-17. “Structural mapping of ligand binding sites on Nav channels
Seven binding sites for toxins and drugs were defined on the primary sequence of Nav channels based on rigorous functional characterizations[79–85]. For instance, receptor site 1 is targeted by the archetypal pore-blocking toxins tetrodo-toxin (TTX) and saxitoxin (STX), and receptor sites 3 and 4 are for α and β-scorpion toxins, respectively (Figure 2a). These high-resolution 3D structures of Nav channels bound to toxins or drugs [56,57,59,61–63,66–68,70,71,74–77,86] implicate the limitation of the definition based on the primary sequence of binding sites, particularly in the PD, which turns out to be a highly versatile host for various small molecules and peptide ligands. In addition, recent findings have unveiled novel binding sites and diverse binding pose…”
According to Li “It should be noted that Nav channels exhibit conformational dynamics upon binding to specific ligands. Some ligands bind to Nav channels in a state-dependent manner. For instance, despite numerous attempts, the density for lidocaine remains invisible and the resolution for funapide and DSP-2230 are limited [67]. One possible reason is that these ligands may prefer different states that are yet to be resolved. Therefore, obtaining structures of Nav channels in different states, such as resting state, is indispensable for drug discovery…..It is noted that conformational dynamics exceeds the current capabilities of AI structure prediction. Hence, obtaining experimental structures of Nav channels at different states in complex with ligands is vital for rational drug design.” [Li page 12] Since it is unclear how the compound binds it is unclear how selective the compound would be on each of the many ion channels, or if the selectivity is even limited to ion channels. Looking at the structure of any hypothetical prophetic compound and deciding if it meets the claimed functional requirements is not possible. Applicants provide no guidance for identifying the compounds that meet the requirements other than trial and error screening. In light of this claim 3 lacks written description.
The fact pattern in this case is similar to that in University of Rochester v. G.D. Searle & Co., 68 USPQ2d 1424 (W.D.N.Y. 2003). In Rochester, there were no compounds known to have the required function. The key similarity between the cases, and the one relevant to this ground of rejection, is the fact that no method (other than trial-and-error) is provided for identifying compounds having the desired function. For this reason, the rejection due to lack of written description is proper.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
6. Claim(s) 1, 3-5, 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Da Silva, Bioorganic. Med. Chem 2010, 18(14), 5007-5015 (cited on the ISR). Page 5008 Scheme 1 teaches the claimed compounds:
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Compounds 2a, 2b, 2c, 2d anticipate the claims where in Formula I R1-R3, R5-R6 are H and R4 is aryl (phenyl, naphthyl, anthracenyl), 2q, 2k, 2r, 2s, where R4 is heteroaryl (pyridinyl, benzodioxole), and 2e, 2f, 2m, 2n, where R4 is R13 where R14-R18 are various including halogen, hydrogen, alkoxy, haloalkyl. “All compounds (2a–s) were evaluated in the screening dose of 100 lmol/kg (po) employing chemical and thermal models of acute pain and inflammatory test” [page 5008]. The compounds were injected as described on page 5014 meeting the kit application claim 15. The compounds “were used as suspensions in arabic gum.”
The language in claim 3, “”characterized in that it is a selective inhibitor of the voltage-gated sodium channels Nav 1.7 and/or Nav 1.8”” is not limiting because the body of claim 1 describes a structurally complete invention and the functional language only refers to properties of that structure. A claim may recite features of a compound functionally, but the patentability of the compound depends upon the claimed structure, not the use or purpose of that structure. Thus, to limit a compound or composition claim, the functional language must result in a structural difference in the claimed compound or composition. This would require a chemical change to atoms of the claimed compound or composition. None of the recited language alters the number of protons in the nucleus of any atom nor adds or removes any atoms from the structure, and the structure is unchanged. Since the language does not structurally limit or affect the compound structure and only states a property of the invention, the language is not limiting. Accordingly, the claim terms do not impart any structural change and therefore have no patentable weight since the structure is capable of performing the intended use. See also MPEP § 2112 - MPEP § 2112.02. Functional language is not limiting where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a functional purpose or intended implementation of the invention. This is grounded in the statutory distinction, between a physical product and activities that constitute a process (which may include a new “use” of a known invention). The recitation of a new intended use for an old product does not make a claim to that old product patentable.
7. Claim(s) 1, 3-5, 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Moffett US 4,017,492. The claims 1, 3-5, 15 are drawn to isomers. The elected species, compound 209 a has a molecular formula of C22H21ClN4O4. Moffett US 4,017,492 on col. 19 lines 1-5 teaches Example 28, 7-Chloro-2-[[1,3-bis(methoxycarbonyl)-propylidene]hydrazino]-5-phenyl-3H-1, 4-benzodiazepine which also has a molecular formula of C22H21ClN4O4, making it an isomer of the elected species. The compound was part of various compositions on column 5 and injected into rats and mice. The syringe serving as device.
8. Claim(s) 1, 3 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by the STN-Chemical Database Registry for Pyrazinecarboxylic acid, 5-chloro-2-[(2,3-difluoro-5-methoxy-4-methylphenyl)methylene]hydrazide, RN 2631957-44-1 entered into STN: 14 Apr 2021. This compound reads on claim 1 where R1 is H, R2 is Cl, R3 is H, R4 is R13 where one of R8/R12 is halogen (F) the other is H, one of R9/R11 is alkoxy the other is halogen (F), R10 is alkyl (methyl), R5 is H, R6 is H, . This compound was entered into Registry and is listed as being commercially available by the company Aurora Fine Chemicals. The on sale bar is also met since the following documentation shows that this material was subject to an offer for sale by a foreign manufacturer which was communicated to a prospective purchaser in the United States. (See CTS Corp. v. Piher Int 'l Corp., 593 F.2d 777, 201 USPQ 649 (7th Cir. 1979). This information was communicated to the prospective purchaser in the United States via the internet as shown by the following, which was dated by the internet archive to April 6, 2007, Online :
"http://web.archive.org/web/20070406205858/http://www.aurorafinechemicals.com/english/order.html" dated April 6, 2007, accessed February 19, 2015.
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, 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.
9. Claims 4-5, 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over S STN-Chemical Database Registry for Pyrazinecarboxylic acid, 5-chloro-2-[(2,3-difluoro-5-methoxy-4-methylphenyl)methylene]hydrazide, RN 2631957-44-1 entered into STN: 14 Apr 2021 as applied to claim 1 and 3 above. This compound reads on claim 1 as discussed above. This compound was entered in the database Chemcats, and is listed as being commercially available by the company Aurora Fine Chemicals. This compound was sold for high throughput screening purposes. Typically such compounds are also sold as solutions in DMSO for cell screening purposes, however no evidence of a solution offered for sale has been obtained. It would be obvious to place the compound in DMSO to facilitate such screening. Similar companies offer the compounds for sale in solution in DMSO. Online: "http://web.archive.org/web/20070630171813/http://www.enamine.net/index.php?option=com_content&task=view&id=22&menuid=51&PHPSESSID=64a4f248f69d671a413f487bb62c4d90" dated June 30, 2007, accessed April 1, 2015. "Format dry powders / DMSO solutions in ENAMINE's or your vials / plates". It would be obvious to place such a compound in a solution with a solvent. Ex parte Douros et al. (POBA 1968) 163 USPQ 667; “It is clearly obvious to add a carrier or solvent to an unpatentable compound. This combination does not become new and patentable because of the presence of the solvent or carrier, Ex parte Billman, 71 USPQ 253 ; In re Riden et al., 50 CCPA 1411, 318 F.2d 760, 1963 C.D. 794, 796 O.G. 863, 138 USPQ 112 ; In re Pieroh et al., 50 CCPA 1471, 319 F.2d 248, 797 O.G. 6, 138 USPQ 238 ; In re Rosicky, 47 CCPA 859, 276 F.2d 656, 755 O.G. 929, 125 USPQ 341, 1960 C.D. 197.”
Objections
10. Claim 2 is objected to for depending from a rejected base claim, but would be allowable in independent format with all the limitations of the base claim and any intervening claim.
Conclusion
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID K O'DELL whose telephone number is (571)272-9071. The examiner can normally be reached on Monday - Friday 9:30 - 7:00 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached on 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DAVID K O'DELL/ Primary Examiner, Art Unit 1621
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