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 .
Status of the Claims
Claims 1, 20-22, 24-30, 32-34, 37-40, 43, and 46 are pending and examined.
Specification
The use of the terms: Triton X100 (page 102), Teledyne RediSep® (page 69) and Biotage ISOLUTE® SCX-II (page 69), among others, which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Allowable Subject Matter
Claim 38 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
Claims 1, 20-22, 24-28, 30, 32, 43, and 46 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by St. John et al., “Targeting zoonotic viruses: Structure-based inhibition of the 3C-like protease from bat coronavirus HKU4 - the likely reservoir host to the human coronavirus that causes Middle East Respiratory Syndrome (MERS),” Bioorganic & Medicinal Chemistry (2015), 23(17), 6036-6048.
St. John teaches anti-viral compounds including the following:
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The compound above is a compound of Formula II of claim 1, wherein: R2a and R2b form an aryl; R2c is hydrogen; R1a and R1b are hydrogen; R1 is a monocyclic heterocycle with one S; X1-X4 are CR3a-3d, wherein R3a-R3d are hydrogen; and R5 is a monocyclic heterocycle with one N.
St. John teaches the claimed compound above (i.e., compound 11A) is a class A peptidomimetic as a target for the anti-coronaviral 3C-like protease which is required for the coronavirus lifecycle. See Abstract. Of the compounds tests 43 3C-like protease inhibitors were identified with inhibitory potency. See p6037, 4th full par. Only compounds with greater than 50% inhibition of HKU4-CoV 3CL at 100 μM were shown. Compound 11A is noted to be a good inhibitor. See p6038, 1st full par.
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.
Claims 1, 20-22, 24-28, 30, 32, 40, 43, and 46 are rejected under 35 U.S.C. 103 as being unpatentable over St. John et al., “Targeting zoonotic viruses: Structure-based inhibition of the 3C-like protease from bat coronavirus HKU4 - the likely reservoir host to the human coronavirus that causes Middle East Respiratory Syndrome (MERS),” Bioorganic & Medicinal Chemistry (2015), 23(17), 6036-6048.
St. John teaches anti-viral compounds including the following:
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The compound above is a compound of Formula II of claim 1, wherein: R2a and R2b form an aryl; R2c is hydrogen; R1a and R1b are hydrogen; R1 is a monocyclic heterocycle with one S; X1-X4 are CR3a-3d, wherein R3a-R3d are hydrogen; and R5 is a monocyclic heterocycle with one N.
St. John teaches the claimed compound above (i.e., compound 11A) is a class A peptidomimetic as a target for the anti-coronaviral 3C-like protease which is required for the coronavirus lifecycle. See Abstract. Of the compounds tests 43 3C-like protease inhibitors were identified with inhibitory potency. See p6037, 4th full par. Only compounds with greater than 50% inhibition of HKU4-CoV 3CL at 100 μM were shown. Compound 11A is noted to be a good inhibitor. See p6038, 1st full par.
It would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the instant application to arrive at the claimed products and methods in view of St. John. One would be motivated to do so because the claimed agent is taught to have anti-viral inhibitory activity against 3C-like protease, which is required for the coronavirus lifecycle. As such, administering this compound to a subject in need therefore would have a reasonable expectation of success in treating the same through such inhibition.
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.
Claims 1, 20-22, 24-30, 32-34, 37, 39, 40, 43, and 46 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for the compounds set forth in claim 38, are not considered enabled for the other compounds encompassed by Formulas (I) and (II). See claim 1 and 20. 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.
The standard for determining whether the Specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? As recognized by the court in In re Wands, 858 F.2d 731 (Fed. Cir. 1988), that is still the standard to be applied, determined by consideration of the Wands factors (MPEP 2164.01(A)); namely, nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered, with the most relevant factors discussed below
Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
In the instant case, the claimed invention pertains to compounds of Formula (I), which are alleged by the Specification to act as 3C-like protease inhibitors (3CLPro).
The State of the Prior Art and the Relative Skill of those in the Art: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed.”
As discussed above, the instantly claimed invention pertains to compounds of Formulas (I) and (II), which are alleged by the Specification to act as 3CLPro inhibitors. At the time the instant application was filed, it would have been known by those of ordinary skill in the art that - due in large part to the strict requirement of complementarity between a compound and its corresponding binding site on a target receptor or enzyme - compounds, in the vast majority of cases, demonstrate a remarkably high correlation between their structure, specificity and ability to produce a pharmacological effect. At the same time, it would have also been generally assumed that two compounds with similar chemical properties would exhibit similar biological effects. Thus, given a series of compounds that are shown to exert an activity of interest (or given a target of interest), the ordinarily skilled artisan would have expected that a limited genus of related compounds (e.g., compounds exhibiting near equal molecular shapes and volumes, approximately the same distribution of electrons, and similar physical properties such as hydrophobicity, etc.) would interact with the given target to elicit a related biological response.
The Level of Predictability in the Art: Once a compound has been identified by ligand based and/or structure based drug design methods as potentially binding to the target molecule, it must be evaluated. Usually, several molecules which scored well during the docking run are evaluated in further tests since even the top scoring molecule could fail in vitro assays… Finally, leads are brought into the wet lab for biochemical evaluation. A low level of predictability is not surprising considering that even minor structural changes can, and frequently will, drastically alter or eradicate a parent compound’s ability to modulate the activity of a specific receptor or enzyme. Indeed, modifying even a single atom in a compound can dramatically change the compound’s overall structure and - even though complementarity in one portion of the compound might be improved by the chemical revision - the overall binding or activity might be severely compromised.
The Amount of Direction Provided by the Inventor / Existence of Working Examples: The amount of direction provided by the Applicant is considered to be determined by the Specification and the working examples. In the instant case, the Specification discloses approximately 100-124 compound species encompassed by Formulas (I) and (II). However, the data on these compounds, which include Table 1 on page 102 and Table 2 on page 105 are limited. The data on these compounds in Table 1 provides SARS CoV-1 and CoV-2 IC50 data. However, data is only presented for 26/102 compounds for CoV-1. The remaining data in the table is filled in with designation “ND.” More importantly, among the compounds that are substantially similar in structure, the values for IC50 are hugely distinct. For example, Table 1 shows that compound 18 has an IC50 of 22.78, compound 17 has an IC50 value of 0.78, compound 41 has an IC50 value of 0.019, and compound 30 has an IC value of greater than 200.
The compounds shown in the Specification and claimed in claim 38 have the following similar structures:
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. The main distinction among the compounds claimed in claim 38 and those shown in the Specification are distinct based on their R1 values and R5 or A. However, there is limited variability among R1 and R5 or A. For example, R1, is thiophene, phenyl, or pyridine optionally substituted with Cl, F, CF3 in all of the compounds in claim 38 with the exception of: approximately 3. Additionally, R1a and R1b are both hydrogen in all compounds of claim 38, thereby forming a -CH2- linking a nitrogen atom with R1 in each example. However, the claims allow for R1a and R1b to be the following:
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Similarly, R5 is a 5 or 6 membered heterocycle with 1-3 nitrogen atoms in all embodiments in claim 38.
Despite the limited variability and the shown substantial distinctions in potency when minor structural variations are presented, the claims include the following definitions for R1 and R5 or A.
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AND
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Even further, with almost no variability in R2a, R2b, R2c, R1a, R1b, X1-X4, there claims provide for substantial breadth.
Scope or Breadth of the Claims: As stated in MPEP 2164.01(c), “when a compound or composition claim is not limited by a recited use, any enabled use that would reasonably correlate with the entire scope of that claim is sufficient to preclude a rejection for nonenablement based on how to use” (emphasis added). Thus, as stated in MPEP 2164.08, “[t]he focus of the examination inquiry is whether everything within the scope of the claim is enabled” (emphasis added). Indeed, the Federal Circuit has repeatedly held that “the specification 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 (Fed. Cir. 1993) (emphasis added).
At the same time, however, it is also recognized that not everything necessary to practice the invention need be disclosed. Nor is it necessary that an Applicant test all the embodiments of his invention. In re Angstadt, 537 F.2d 498 (CCPA 1976) (emphasis added). In fact, as stated by the court in In re Buchner, 929 F.2d 660 (Fed. Cir. 1991), a patent need not teach, and preferably omits, what is well known in the art.
Accordingly, for purposes of enablement, the relevant concern is whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate in scope with the protection sought by the claims. Thus, while “a patent application is entitled to claim his invention generically” it is necessary that “he provide a disclosure sufficient to enable one skilled in the art to carry out the invention commensurate with the scope of his claims". Amgen, Inc., v. Chugai Pharmaceutical Co., Ltd. (Fed. Cir. 1991). As noted by the court in In re Fisher, 427 F.2d 833 (CCPA 1970), the scope of enablement must bear a “reasonable correlation” to the scope of the claims. See also Ak Steel Corp. v. Sollac, 344 F.3d 1234 (Fed. Cir. 2003) and In re Moore, 439 F.2d 1232 (CCPA 1971). As stated in MPEP 2164.08, resolution of this concern requires two stages of inquiry: “[t]he first is to determine how broad the claim is with respect to the disclosure. The entire claim must be considered. The second inquiry is to determine if one skilled in the art is enabled to make and use the entire scope of the claim without undue experimentation”.
As to the first inquiry, as discussed above, the claims are drawn to compounds of Formula (I), which are alleged by the Specification to as PARP-7 inhibitors. Considering that Formula (I) encompasses tens of thousands of compound species or more, it is evident that the claims are broad. Yet, as discussed above, the instant Specification discloses approximately 87 similarly structured compound species encompassed by Formula (I) as recited by the claims. As such, the claim is extremely broad with respect to the disclosure. The second inquiry is discussed in detail below.
Amount of Experimentation Necessary: In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the entire scope of the invention as claimed. As discussed above, the claims are drawn to compounds of Formula (I) and (II), which are alleged by the Specification to act as 3CLPro inhibitors. Since identifying any compound which is capable of modulating the activity of a specific receptor, ion channel, or enzyme is extremely complex, the nature of the instant invention considered to be one of extreme complexity. In the instant case, this complexity is exacerbated by the broadness of Formulas (I) and (II) with respect to the disclosure since they encompasses thousands of compound species, whereas the instant Specification discloses approximately 100 such compound species exerting a disclosed activity. Although the relative skill of those in the art to which the invention pertains is high, the state of the art and unpredictability within the art is such that even the most talented artisan (armed with screening techniques including computer assisted virtual screening techniques such as ligand-based and structure-based design methods) could not reasonably predict which of the thousands of compounds encompassed by Formulas (I) and (II) would exert the alleged activity based on the limited disclosure of similarly structured active compounds with a high degree of variability. Although the skilled artisan would have known that certain chemical modifications to the disclosed compounds may predictably provide structurally related compounds having similarly activity, the skilled artisan would have also known that even minor structural changes can, and frequently will, drastically alter or eradicate a parent compound’s ability to modulate the activity of a specific receptor or enzyme.
As noted above, the data on these compounds in Table 1 of the Specification provides SARS CoV-1 and CoV-2 IC50 data. However, data is only presented for 26/102 compounds for CoV-1. The remaining data in the table is filled in with designation “ND.” More importantly, among the compounds that are substantially similar in structure, the values for IC50 are hugely distinct. For example, Table 1 shows that compound 18 has an IC50 of 22.78, compound 17 has an IC50 value of 0.78, compound 41 has an IC50 value of 0.019, and compound 30 has an IC value of greater than 200.
Not only are the synthesized compounds limited substantially in their structures relative to the breadth of the claims, but the variability and data to any degree is lacking with respect to IC50 3CLPro inhibition data.
Thus, in order to identify usable compounds of Formulas (I) and (II), the skilled artisan (at minimum) would have to carry out ligand based drug design methods using the approximately 100 disclosed compounds as a starting point and, assuming the structure of the target receptor was known, combine the findings with data derived from structure based drug design methods to arrive at a small library of “lead” compounds believed to possess the activity of interest. The skilled artisan would then synthesize lead compounds that are within Formula (I) for in vitro testing. Given the unpredictability of the chemical arts, it is highly unpredictable whether any compound within the subgenus of compounds of Formula (I) identified by rational drug design based on the instant disclosure would, in fact, be usable. Whether the other compounds of Formula (I) (i.e., those not identified by rational drug design based on the instant disclosure) would be usable is even less predictable. As such, the only way to ascertain which of the hundreds of millions, and potentially billions, of claimed compounds encompassed by Formula (I) are usable based on the limited disclosure would require undue experimentation. That is, the only way one skilled in the art is enabled to use the entire scope of the claim based on the instant disclosure entails undue experimentation.
To overcome this rejection, Applicant should narrow the scope of the claims such that they bear a reasonable correlation with the disclosure.
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.
Claims 40, 43, and 46 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for inhibiting 3CLPro with specific compounds of claim 38, e.g., with different degrees of in vitro potency and those conditions known to be represented by such model, are not considered enabled for treating all viral infections and inhibiting viral replication of all viruses.
The standard for determining whether the Specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? As recognized by the court in In re Wands, 858 F.2d 731 (Fed. Cir. 1988), that is still the standard to be applied, determined by consideration of the Wands factors (MPEP 2164.01(A)); namely, nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered, with the most relevant factors discussed below
Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
In the instant case, the claimed invention pertains to compounds of Formula (I-1), which are alleged by the Specification to prevent and treat all forms of cancer, autoimmune disorders, and others.
The State of the Prior Art and the Relative Skill of those in the Art: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed.”
According to Cleveland Clinic, protease inhibitors can treat certain viral infections and they are only approved to treat specific viral infections. This includes HIV/AIDS, Hepatitis C, and COVID-19. See https://my.clevelandclinic.org/health/treatments/24937-protease-inhibitors- date accessed March 3, 2026.
There is no indication that a 3CL protease inhibitor can treat all viruses.
As discussed above, the instantly claimed invention pertains to compounds of Formula (I-1), which are alleged by the Specification to treat conditions as an inhibitor of 3CLPro. At the time the instant application was filed, it would have been known by those of ordinary skill in the art that - compounds, in the vast majority of cases, demonstrate a remarkably high correlation between their structure, specificity and ability to produce a pharmacological effect. At the same time, it would have also been generally assumed that two compounds with similar chemical properties would exhibit similar biological effects. Thus, given a series of compounds that are shown to exert an activity of interest (or given a target of interest), the ordinarily skilled artisan would have expected that a limited genus of related compounds (e.g., compounds exhibiting near equal molecular shapes and volumes, approximately the same distribution of electrons, and similar physical properties such as hydrophobicity, etc.) would interact with the given target to elicit a related biological response.
Accordingly, at the time the invention was made, the relative skill of those in the art tasked with identifying compounds exerting an activity of interest would have been high, as the ordinarily skilled artisan would have had, at minimum, a Ph.D. and experience with screening techniques including computer assisted virtual screening techniques such as ligand-based and structure-based design methods. Deciding which technique to use would have been determined by the skilled artisan’s knowledge regarding the compound and target of interest. Ligand based drug design relies on knowledge of a compound or compounds of interest (i.e., ligands) to derive new compounds that will, in theory, similarly interact with the target of interest to elicit the activity of interest. Conversely, structure based drug design relies on knowledge of the three dimensional structure of the target of interest (i.e., receptor, ion channel, or enzyme) to derive new compounds that will, in theory, interact with the target of interest to elicit the activity of interest. In either case, the compounds derived from these techniques (applied alone or in combination) are then subjected to in vitro testing for validation.
The Level of Predictability in the Art: Once a compound has been identified by ligand based and/or structure based drug design methods as potentially binding to the target molecule, it must be evaluated. However, as discussed by Anderson (Chem and Biol 10:787-797, 2003), “it is important to consider that the ranking assigned by the scoring function is not always indicative of a true binding constant, since the model of the target:ligand interaction is inherently an approximation. Usually, several molecules which scored well during the docking run are evaluated in further tests since even the top scoring molecule could fail in vitro assays… Finally, leads are brought into the wet lab for biochemical evaluation” (Page 794, Column 1). By that point, as noted by Thiel (Nature Biotechnol 2:513-519, 2004), “libraries are small and hit rates are on the order of one in ten” (Page 517, Column 2). This low level of predictability is not surprising considering that even minor structural changes can, and frequently will, drastically alter or eradicate a parent compound’s ability to modulate the activity of a specific receptor or enzyme. Indeed, modifying even a single atom in a compound can dramatically change the compound’s overall structure and - even though complementarity in one portion of the compound might be improved by the chemical revision - the overall binding or activity might be severely compromised. This is certainly true in the case. For example, comparing the structures of those compounds of claim 14, they appear relatively similar. However, the in vitro IC50 3CLPro inhibitory data show substantial differences in in vitro efficacy. Thus, each change in structure must be evaluated for drastic changes in efficacy.
The Amount of Direction Provided by the Inventor / Existence of Working Examples: The amount of direction provided by the Applicant is considered to be determined by the Specification and the working examples. In the instant case, the Specification discloses data on approximately 100 compounds species encompassed by Formula (I) that shows activity for in vitro SARS-CoV-1 and SARS-CoV-2 inhibitory IC50. See Specification pp102-103. The variability in results is substantial ranging from low to high and this includes for almost identical compounds. Moreover, data is only provided for 23/109 compounds for SARS-CoV-1 IC50 inhibition. Data is shown as “ND” for the remaining compounds. See Table 1. Further, Tables 1 and 2 provide data for SARS CoV virus. There is not a single example in vitro or in vivo of any other virus being treatable or preventable. While a CPE inhibition assay was performed and shown in Table 2 on page 105, only 11 compounds were tested with huge differences in IC value wherein values range from 0.558 for compound 41 to 16.69 for compound 35. There is no data on the breadth of the compounds claimed even with respect to those specific compounds set forth in claim 38.
Scope or Breadth of the Claims: As stated in MPEP 2164.01(c), “when a compound or composition claim is not limited by a recited use, any enabled use that would reasonably correlate with the entire scope of that claim is sufficient to preclude a rejection for nonenablement based on how to use” (emphasis added). Thus, as stated in MPEP 2164.08, “[t]he focus of the examination inquiry is whether everything within the scope of the claim is enabled” (emphasis added). Indeed, the Federal Circuit has repeatedly held that “the specification 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 (Fed. Cir. 1993) (emphasis added).
At the same time, however, it is also recognized that not everything necessary to practice the invention need be disclosed. Nor is it necessary that an Applicant test all the embodiments of his invention. In re Angstadt, 537 F.2d 498 (CCPA 1976) (emphasis added). In fact, as stated by the court in In re Buchner, 929 F.2d 660 (Fed. Cir. 1991), a patent need not teach, and preferably omits, what is well known in the art.
Accordingly, for purposes of enablement, the relevant concern is whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate in scope with the protection sought by the claims. Thus, while “a patent application is entitled to claim his invention generically” it is necessary that “he provide a disclosure sufficient to enable one skilled in the art to carry out the invention commensurate with the scope of his claims". Amgen, Inc., v. Chugai Pharmaceutical Co., Ltd. (Fed. Cir. 1991). As noted by the court in In re Fisher, 427 F.2d 833 (CCPA 1970), the scope of enablement must bear a “reasonable correlation” to the scope of the claims. See also Ak Steel Corp. v. Sollac, 344 F.3d 1234 (Fed. Cir. 2003) and In re Moore, 439 F.2d 1232 (CCPA 1971). As stated in MPEP 2164.08, resolution of this concern requires two stages of inquiry: “[t]he first is to determine how broad the claim is with respect to the disclosure. The entire claim must be considered. The second inquiry is to determine if one skilled in the art is enabled to make and use the entire scope of the claim without undue experimentation”.
As to the first inquiry, as discussed above, the claims are drawn to compounds of Formulas (I) and (II), which are alleged by the Specification as inhibitors of CLPro. Considering that the conditions claimed includes all viruses with thousands of compounds, it is evident that the claims are broad. Yet, as discussed above, the instant Specification discloses only 100 similarly structured compound species and slight deviations in those structures yield substantially different IC50 values. Despite the variability in efficacy and the lack of an any in vivo assay, there instant claims are directed to treating and inhibiting all viruses. As such, the claim is extremely broad with respect to the disclosure. The second inquiry is discussed in detail below. With respect to a subject population, there is not a single example of a virus being tested other than SARS-CoV-1 and SARS-CoV-2.
Amount of Experimentation Necessary: In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the entire scope of the invention as claimed. As discussed above, the claims are drawn to compounds of Formula (I-1), which are alleged by the Specification to inhibit CLPro. Since identifying any compound which is capable of modulating the activity of a specific receptor, ion channel, or enzyme is extremely complex, the nature of the instant invention considered to be one of extreme complexity. In the instant case, this complexity is exacerbated by the broadness of Formula (I) with respect to the disclosure since Formula (I) encompasses thousands of compound species, whereas the instant Specification discloses only 100 such compound species low and high in vitro IC50 inhibitory activity. Although the relative skill of those in the art to which the invention pertains is high, the state of the art and unpredictability within the art is such that even the most talented artisan (armed with screening techniques including computer assisted virtual screening techniques such as ligand-based and structure-based design methods) could not reasonably predict which of the hundreds of millions of compounds encompassed by Formula (I) would exert the alleged activity based on the limited disclosure of 87 compounds comprising discrepancies in activity. Although the skilled artisan would have known that certain chemical modifications to the disclosed compounds may predictably provide structurally related compounds having similarly activity, the skilled artisan would have also known that even minor structural changes can, and frequently will, drastically alter or eradicate a parent compound’s ability to modulate the activity of a specific receptor or enzyme.
The quantity of experimentation needed
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to definitively determine the specific population of individuals who would need to be treated and would furthermore have to determine which of the claimed compounds would provide for the prevention and treatment of all viruses. To treat and inhibit all viruses would require undue experimentation to both develop an animal model which would reasonably correlate with all forms of viruses and viral replication and also to identify the portion of the population in which the instantly claimed compounds would need to necessarily be administered.
Thus, factors such as "sufficient working examples", "the level of skill in the art" and "predictability", etc. have been demonstrated to be sufficiently lacking in the instantly claimed methods. In view of the breadth of the claim, the chemical nature of the invention, and the lack of working examples regarding the activity of the claimed compounds, one having ordinary skill in the art would have to undergo an undue amount of experimentation to use the invention commensurate in scope with the claims.
The court in Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001, states that, “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which diseases can be treated or prevented by the compound encompassed in the instant claims, with no assurance of success.
To overcome this rejection, Applicant should narrow the scope of the claims such that they bear a reasonable correlation with the disclosure.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 20-22, 24-28, 30, 32, 43, and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7-10, 14, 15, 17-19, 21, 23, 24, 25, and 28 of copending Application No. 18/570,520. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims include overlapping compounds and they include compounds that are also being used to treat viral infections and inhibit viral replication. The variable “B” in the ‘520 application can be a bicyclic heteroaryl group. The distinction is that the B group of the ‘520 application and the bicyclic group of the instant application have different points of attachment in what can include identical structures otherwise. The instant application requires the bicyclic group to attach to the remainder of the molecule through a nitrogen atom while the ‘520 application attaches “via a carbon atom.” The examiner notes that isomers used for a same purpose and structurally identical otherwise are consider obvious variants absent evidence to the contrary. The R4 and R1 variables and other components can be identical. Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D BARSKY whose telephone number is (571)272-2795. The examiner can normally be reached on 9-5 M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy 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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/JARED BARSKY/Primary Examiner, Art Unit 1628