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 .
Reissue Applications
For reissue applications filed on or after September 16, 2012, all references to 35 U.S.C. 251 and 37 CFR 1.172, 1.175, and 3.73 are to the current provisions. This application, filed August 1, 2025, is a reissue of U.S. Patent 11,712,435 (hereafter the '435 patent), which issued from U.S. application Serial No. 16/967,924 (the ‘924 application) with claims 1-19 on August 1, 2023.
Claims Under Reissue
In examination, reissue application claims are construed broadly. In re Reuter, 651 F.2d 751, USPQ 249 (CCPA 1981) (claims given "their broadest reasonable interpretation consistent with specification"). Claims 1-19 are subject to examination. Claims 1 and 17 are representative and reproduced below:
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17. (Original) A method for treating disease, disorder, or condition the method comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a compound of claim 1.
Reissue Declaration and 35 USC 251
The reissue oath/declarations filed with this application are defective because they fail to identify at least one error which is relied upon to support the reissue application. See 37 CFR 1.175 and MPEP § 1414.
The reissue declarations filed this application do not provide any statement of error and thus, are defective.
It is further noted that since the instant reissue application is a broadening reissue application, the error statement in the reissue declaration must identify a claim that the application seeks to broaden. A general statement, e.g., that all claims are broadened, is not sufficient to satisfy this requirement. In specifically identifying the error as required by 37 CFR 1.175(a), it is sufficient that the reissue oath/declaration identify the issued claim being broadened and a single word, phrase, or expression in the issued claim, and how it renders the original patent wholly or partly inoperative or invalid. The corresponding corrective action which has been taken to correct the original patent need not be identified in the oath/declaration. See MPEP 1414.II(B).
An example of a suitable error statement is as follows:
This is a broadening reissue application. Claim 1 is to be broadened. Claim 1 improperly recites the term “-(CR4R5)m-P(=O)(O-)-O-(CR7R8)p-O-(C=O)-O-R6”. The term is broadened to be “-(CR4R5)m-O-P(=O)(O-)-O-(CR7R8)p-O-(C=O)-O-R6”.
Furthermore, the reissue declarations by assignee for the Institute of Organic Chemistry and by Biochemistry AS CR v.v.i. are signed by the some of the inventors. Clarification in requested as to whether the inventors were intended to sign for the assignee, or if the declarations should have been reissue declarations by the inventors. If Applicant intends to file a reissue declaration by the inventors, then all inventors must sign the declaration.
Claims 1-19 are rejected as being based upon defective reissue declarations under 35 U.S.C. 251 as set forth above. See 37 CFR 1.175.
The nature of the defect(s) in the reissue declarations is set forth in the discussion above in this Office action.
Claim Rejections - 35 USC § 112
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.
Claim 17 is 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 treatment of cancer with the claimed compound as in claims 18 and 19, does not reasonably provide enablement for treating the full scope of the claim, i.e., treating “disease disorder, or condition” with the claimed compound. 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 the claim.
As stated in the MPEP § 2164.01(a): “In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is ‘reasonable’ or is ‘undue.’ Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024).” These factors include the following:
Breadth of claims and nature of the invention: As noted above, claim 17 is broad, encompassing the treatment of any disease, disorder or condition with the claimed genus of compounds, which are prodrugs of mebendazole (MBZ). The claimed genus encompasses thousands of prodrugs.
Furthermore, as noted in “How Many Diseases Exist in the Word,” Neuralword, Oct. 13, 2023 (hereinafter “Neuralword”), there are about 30,000 different diseases know to humanity. These include contagious diseases, non-communicable diseases, genetic disorders, autoimmune diseases and many other categories that affect various parts of the body (see the third page). In fact, new diseases continue to emerge due to factors such as changes in the environment, globalization and the evolution of pathogens. Recent examples include Ebola, Zika and COVID-19 (see fourth page). Neuralword notes that it is challenging to even determine the exact number of diseases that exist in the world (see fourth page).
The state of the prior art: The pharmacological art requires the screening of potential drug candidates in vitro and in vivo to determine if the drug candidates exhibit the desired pharmacological activities.
In order to treat a disease, one would need to precisely identify what the disease is, identify what biological target is connected with the disease, demonstrate that the drug candidate in some way modulates the normal processes of the biological target, and demonstrate that a patient benefited from such modification without detrimental side effects. Typically, this process includes in vitro laboratory screening, preclinical in vivo screening, and three phases of clinical trials. Once this arduous process has been successfully completed by a drug candidate, subsequent drug candidates will benefit from the established proof of concept. The subsequent drug candidates must demonstrate a substantial correlation between their biological activity and that of the known drug candidate.
In the instant case, as acknowledged in the Background section of the ‘435 patent, MBZ was known as a broad-spectrum anthelmintic (i.e., anti-worm medication) and for treatment of cancer (see col. 1, lines 8-16).
The predictability or unpredictability of the art: The pharmaceutical art is recognized as an unpredictable art. As noted by Dobie, “The Reality of Drug Discovery and Development,” Centre for Human Specific Research, 12 December 2024, “[d]rug discovery and development has become an increasingly costly and inefficient process. Despite the enormous resources funneled into each drug candidate, a staggering number of them fail to ever reach the market.” (See the first page). Dobie further teaches that “[t]he reality of drug development is that success in preclinical testing offers no guarantees in clinical trials. Although the rate of successful phase completion varies depending on the source data, it remains clear that transitioning one phase to another is often no more certain than a coin toss.” (See the tenth page). As noted in case law, each embodiment must be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18 (CCPA 1970).
The amount of direction or guidance presented: The instant specification discusses use of MBZ for treatment of parasitic worm infections and cancer (see col. 1, lines 8-16; col. 24, lines 55; col. 55, lines 16-20). However, no other disease, condition or disorder is discussed.
The amount of guidance or direction to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. MPEP § 2164.03 (quoting In re Fisher, 427 F.2d 833, 839, 166 USPQ 18 24 (CCPA 1970)). As identified supra, the pharmaceutical art is recognized as unpredictable. Thus, in order to support a claim for treating any disease, disorder or condition, a vast amount of evidence is required. Such evidence is not present in the instant specification.
The presence or absence of working examples: There are no working or prophetic examples in the specification that demonstrate the treatment of any disease, disorder or condition with any compound in the claimed prodrug genus.
The quantity of experimentation necessary: Generally speaking, the amount of experimentation to transform a molecule into medicine is vast and, as noted above, the success thereof is low. Dobie, as well as Schafer et al (Drug Discovery Today, 2008, 13 (21/22), pp. 913-916, hereinafter “Schafer”), make clear that there are many steps necessary to promote a new molecular entity toward its clinical use, any one of which is cumbersome.
For instance, Schafer discloses: "proof of concept trials have failed when the decision to enter clinical development was based on preclinical experiments using the wrong compound, the wrong experimental model, or the wrong endpoint.” It can be gleaned from this article that a plethora of experimentation is needed to identify a lead compound to establish which preclinical tests are predictive of clinical success, and to establish which diseases are the best to target for each lead compound.
There is generally a vast amount of experimentation to take a drug from bench to the clinic. See e.g., Horig et al (Journal of Translational Medicine, 2004, 2(44), pp. 1-8, hereinafter “Horig”). Horig teaches that “[s]uccessful drug development requires satisfying a matrix of domains from relevance to the disease and the drug-ability of the target through feasibility and convenience of drug delivery, demonstration of favorable benefit-risk profile in order to achieve a drug label that reflects physician and patent acceptance." (See p. 1). The amount of experimentation required to enable a pharmaceutical drug is extensive.
The level of skill in the art: The level of ordinary skill in the art may be found by inquiring into: (1) the type of problems encountered in the art; (2) prior art solutions to those problems; (3) the rapidity with which innovations are made; (4) the sophistication of the technology; and (5) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of those factors may not be present in every case, and one or more of them may predominate. Envil. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983).
Based on the typical education level of the active workers in the field of pharmaceuticals and/or medicine, as well as the high degree of sophistication required to solve problems encountered in the art, a person of ordinary skill in the art would have at least a college degree in a field related to medicine and/or the pharmaceutical art and at least four years of work experience, i.e. a masters or doctorate level scientist/clinician.
Conclusion — Claim 17 is rejected for lack of enablement since the Wands factors lead to a conclusion that the skilled artisan would not be able to make and use the instant invention without undue experimentation, although the level of skill for an ordinary person in the art is high. That is, due to the breadth of the claims, the unpredictability of the art, the lack of guidance or direction from the disclosure, the lack of any working examples, and the amount of experimentation needed illustrate that a person having ordinary skill in the art would not be able to treat the diseases, disorders, or conditions encompassed by claim 17.
Duty to Disclose
Applicant is reminded of the continuing obligation under 37 CFR 1.178(b), to timely apprise the Office of any prior or concurrent proceed-ing in which Patent No. 11,712,425 is or was involved. These proceedings would include interferences, reissues, reexaminations, and litigation. Applicant is further reminded of the continuing obligation under 37 CFR 1.56, to timely apprise the Office of any information which is mate-rial to patentability of the claims under consideration in this reissue appli-cation. These obligations rest with each individual associated with the filing and prosecution of this application for reissue. See also MPEP §§ 1404, 1442.01 and 1442.04.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALAN D DIAMOND whose telephone number is (571)272-1338. The examiner can normally be reached Monday through Thursday 5:30 am to 3:00 pm, and Fridays from 5:30 am to 9:30 am.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Patricia Engle can be reached on 571-272-6660. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Signed:
/ALAN D DIAMOND/Patent Reexamination Specialist
Central Reexamination Unit 3991
Conferees:
/JOSEPH R KOSACK/Patent Reexamination Specialist
Central Reexamination Unit 3991
/Patricia L Engle/SPRS, Art Unit 3991
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