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/EP2022/055561 03/04/2022. FOREIGN APPLICATIONS: EP 21160742.9 03/04/2021 and EP 21206420.8 11/04/2021.
Claims 1, 4-10, 12 are pending.
Response to Arguments
2. The rejection of claims 1-4, 6-10, 12 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for prodrugs is withdrawn based upon the amendments. The rejection of claim 1-4, 6-10, 12 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subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention for the parenthetical phrases is withdrawn based upon the amendments. The rejections of claim 8 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for structures with too many bonds to carbon atoms and under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form are withdrawn based upon the amendments. The rejection of claim(s) 1-4, 6-10, 12 under 35 U.S.C. 102(a)(1) as being anticipated by Carson US 20180110784 A1 is withdrawn based upon the amendments. The rejection of claim(s) 1-4, 6-7, 9, 12 under 35 U.S.C. 103 as being unpatentable over Khalil is withdrawn based upon the amendments. The rejection of claim(s) 1-4, 6-7, 10, 12 under 35 U.S.C. 103 as being unpatentable over Chan and Yu is withdrawn based upon the amendments.
The rejection of claims 1, 4-10, 12 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating cancer with the compounds of claim 8, it does not reasonably provide enablement for the full scope of compounds and the full scope of diseases is maintained. The claims are drawn to an unknown set of diseases described only as “associated with activation of receptor tyrosine-protein kinase ERBB4” while as shown in the rejection cancer is the only disease associated with this receptor. In addition, the generic claims are not commensurate in scope with the disclosed compounds structurally. The specification provides no source for the compounds other than the purchasing from some companies. Since the specification is completely lacking information of how prepare the compounds or references to the information the claimed genus is not enabled.
Applicant’s election of the species, compound 8 in claim 14, in the reply filed on January 23, 2026 was acknowledged. The election was made without traverse. According to applicants’ representative claims 1-4, 6-10, 12 read on the elected species. The generic claim encompassing the elected species is not rejected over the art and as such the search and examination was continued. Accordingly, claim 5, is no longer withdrawn.
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.
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.
3. Claim 1, 4-10, 12 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 treating cancer with the compounds of claim 8, it does not reasonably provide enablement for the full scope of compounds and the full scope of diseases. 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.”
The claims are very broad encompassing a very large number of compounds with various substituents forming various rings, all heterocycles, carbocycles and other groups bearing multiple substitutions. This is a medical invention, but requires the synthesis of compounds or other method obtaining the compounds and such compounds should have biological activity. The specification gives 8 examples of compounds, those in claim 8, which appear on page 72. There is no direction or source for obtaining the compounds from the specification. The examiner conducted a search and found that the compounds are commercial compounds.1 They are sold by various companies, Ambinter, Enamine and Aurora. These companies, while selling some compounds, offer no details of how they are made. As per MPEP:
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
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, 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
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, 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. Rather we find no direction as to how any compound could be obtained. Assuming one would come up with some new synthetic methods, the many required staring materials with these vast substituents are also not known. The limitations of synthetic chemistry is readily apparent as stated in the preface to a recent treatise:
“Most non-chemists would probably be horrified if they were to learn how many attempted syntheses fail, and how inefficient research chemists are. The ratio of successful to unsuccessful chemical experiments in a normal research laboratory is far below unity, and synthetic research chemists, in the same way as most scientists, spend most of their time working out what went wrong, and why. Despite the many pitfalls lurking in organic synthesis, most organic chemistry textbooks and research articles do give the impression that organic reactions just proceed smoothly and that the total synthesis of complex natural products, for instance, is maybe a labor-intensive but otherwise undemanding task. In fact, most syntheses of structurally complex natural products are the result of several years of hard work by a team of chemists, with almost every step requiring careful optimization. The final synthesis usually looks quite different from that originally planned, because of unexpected difficulties encountered in the initially chosen synthetic sequence. Only the seasoned practitioner who has experienced for himself the many failures and frustrations which the development (sometimes even the repetition) of a synthesis usually implies will be able to appraise such work……Chemists tend not to publish negative results, because these are, as opposed to positive results, never definite (and far too copious) [preface]…….even structurally simple compounds often turn out not to be so easy to make as initially thought. [pg. 2]……….…….. As illustrated by the examples discussed below, a good retrosynthesis requires much synthetic experience, a broad knowledge of chemical reactivity, and the ability to rapidly recognize synthetically accessible substructures [pg. 3]…….. As will be shown throughout this book, the outcome of organic reactions is highly dependent on all structural features of a given starting material, and unexpected products may readily be formed. [8]……...Even the most experienced chemist will not be able to foresee all potential pitfalls of a synthesis, specially so if multifunctional, structurally complex intermediates must be prepared. The close proximity or conformational fixation of functional groups in a large molecule can alter their reactivity to such an extent that even simple chemical transformations can no longer be performed. Small structural variations of polyfunctional substrates might, therefore, bring about an unforeseeable change in reactivity [pg. 9]…..” Dorwald F. A. Side Reactions in Organic Synthesis, 2005, Wiley: VCH, Weinheim pg. IX of Preface pg. 1-15.
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).
While these chemical limitations are significant, there is no explanation as to the important structural features for interaction with “receptor tyrosine protein kinase” ERBB4. ERBB4 (Erb-b2 receptor tyrosine kinase 4), also known as HER4, is a transmembrane tyrosine kinase receptor in the epidermal growth factor (EGFR) family. The medicinal chemistry of ERRB4 is relatively well-developed and many limitations are well known in the art. It is sensitive to structural changes that may be relatively minor in the chemical sense see Elwaie J. Med. Chem. 2020, 63, 24, 15906–15945. Figure 1 shows the binding site:
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In this case these compounds bear a remarkable structural resemblance to one another, yet the claims are not commensurate in scope. 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 only eight working examples in this unpredictable art without undue experimentation.
The compounds are shown to inhibit ErbB4. While originally developed for treating breast cancer, Roy “Beyond Trastuzumab: Small Molecule Tyrosine Kinase Inhibitors in HER-2–Positive Breast Cancer” The Oncologist 2009;14:1061–1069, Excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor. ErbB-1 and ErbB-2 are found in many human cancers, and their excessive signaling may be critical factors in the development and malignancy of these tumors.
Oh “HER2-targeted therapies — a role beyond breast cancer” Nature Reviews Clinical Oncology Reviews January 2020 volume 17 | | 33, figure 2 shows expression profiles of HER2 in other cancers:
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Her 2 is expressed in additional cancers and these compounds can also treat other cancers. While success is not guaranteed, at least gastric cancer was treated this way. Beyond these cancers there is no indication that HER2 inhibitors could be used to treat all the diseases in claims 9-10.
Conclusion
4. 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 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 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
1 See attached 5 page STN printout from March 16, 2026.
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