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 .
Response to Amendments
Applicant’s amendments to the claims of November 20, 2025, in response to the Office Action of August 20, 2025, are acknowledged.
Response to Arguments
The § 112 indefiniteness rejections are withdrawn in view of the amendments to the claims.
Applicant traverses the Scope of Enablement rejection by indicating that all claimed embodiments do not need to be shown and there is variability shown in the Specification.
The examiner notes that there is limited to no variability shown for Ring A, linker L, and X-Y in the Specification among compounds that, as discussed below, show substantial discrepancies in IC50 values despite minor structural distinctions among compounds. The examiner notes the following:
Ring A while being required to be piperidinyl, is also “optionally substituted with one more substituents selected from alkyl, CN, cycloalkyl, OH, alkoxy, halo, haloalkyl, and heteroaryl, wherein said heteroaryl group is in turn optionally further substituted with one or more groups selected from halo and alkyl.” Among the 73 examples in the Specification, Ring is substituted in 0/73 embodiments. Not a single substituent of any kind is included.
Linker L is defined to include
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However, the Specification includes the following: Ring-C1-C4 alkyl or alkylene-O-Ring. This is the breadth of variability in all 73 embodiments in the Specification. A C1-C4 carbon chain attaches to an oxygen and the oxygen is directly attached to the R4-R1 comprising phenyl ring structure.
Finally, with respect to variable X-Y, the examiner notes: This combination is defined to include NR23SO2 or SO2R23. R23 is defined by the claims to include a hydrogen or alkyl. Alkyl is defined to include a straight or branched chain alkyl radical, preferably C1-20 alkyl. See p8. However, in all 73 of the embodiments in the Specification, R23 is hydrogen. It is not clear if a compound with a hydrogen compared to a C20 alkyl would be similarly efficacious.
Overall, the variability for Ring A substituents, Linker L, and R23 is almost non-existent. The claims must be structured to bear a reasonable proportion to the support provided in the Specification. Those claims that achieve this are noted as allowable.
With respect to Applicant’s traversal of the Scope of Enablement Rejection for prevention and the breadth of conditions, Applicant notes that they have amended to the claims to specify an “ERAP-1-associated disorder or cancer.”
The examiner notes that treating or preventing all viral disorders, immune disorders, inflammatory disorders, and cancers is not enabled. There is no indicating that the claimed compounds can treat or prevent this breadth of diseases. There is no indication that the claimed agents can prevent any condition. ERAP-1 associated is defined as “inappropriate” ERAP1 activity. This could include high or low levels or slightly modified levels. The Specification fails to provide a single examples of prevention or treatment of any kind. There is a single OVA antigen presentation assay performed as described on pages 169-170 of the Specification. There is no link to preventing or treating claimed conditions. Applicant’s argument in this respect is not persuasive.
Wagner et al., “Down-regulation of ERAP1 mRNA expression in non-small cell lung cancer,” BMC Cancer. 2023 Apr 26;23(1):383, teaches: “Down-regulation of ERAP1 mRNA observed in NSCLC tissue may be related to tumor immune evasion strategy.”
Reeves et al., The role of polymorphic ERAP1 in autoinflammatory disease,” Bioscience Reports (2018) 38, teaches: “These encouraging results, in the context of cancer, have shown that reducing ERAP1/ERAP2 activity can alter the immune response, which may well prove protective in AS and BSCR. Alternatively, activating ERAP1 may prove useful in diseases such as BD, where ERAP1 associated with disease has reduced function.”
As such, it is not established that the same compound can prevent any condition and it is not established that the same compound can treat an ERAP1-associated condition while the state of the art establishes that treatment can require upregulating or downregulating ERAP1 to treat claimed conditions.
Status of the Claims
Claims 1, 2, 5, 6, 8, 10, 12, 14, 16, 18, 20, 21, 23-32, 34, 35, 37, 38, 40-43, 45, 50-53, 56-58, 61, 62, 65, 68, and 69 are pending and examined.
Claim Objections-
(Allowable but dependent upon rejected base claim)
Claims 24-32, 40, 62, 65, 68, and 69 are 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 § 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, 2, 5, 6, 8, 10, 12, 14, 16, 18, 20, 21, 34, 35, 37, 38, 41, 42, 50, 51, 52, 53, 56-58, and 61 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for the elected compound species and those embodied by the instant Specification and claim 40, is not considered enabled for the other compound species encompassed by Formula (I-1). 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-1), which are alleged by the Specification to act as ERAP1 inhibitors.
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 Formula (I), which are alleged by the Specification to act as ERAP1 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 73 compound species encompassed by Formula (I-1), which are ERAP1 inhibitors.
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 ERAP1 inhibitors. Considering that Formula (I) encompasses thousands of compound species, it is evident that the claims are broad. Yet, as discussed above, the instant Specification discloses approximately 73 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-1), which are alleged by the Specification to act as ERAP1 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 Formula (I-1) with respect to the disclosure since Formula (I-1) encompasses at least thousands of compound species, whereas the instant Specification discloses only 73 such compound species exerting the 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 Formula (I-1) would exert the alleged activity based on the limited disclosure of 73 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.
In this particular case, the 73 compounds taught by the Specification are split with activity level. For example, 13 of those compounds have low activity defined as an IC50 of >1000nM, whereas there are also many compound with high activity defined as an IC50 of <250nM. Compounds 1 and 2 are high and low activity compounds, shown below.
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.
Despite the mostly identical compound with a difference in only R7 and linker, the variability is substantial as measured in IC50 value. Despite this, Ring A can be any 5-7 membered heterocycloalkyl ring with one or more alky, CN, cycloalkyl, OH, alkoxy, halo, haloalkyl, and heteroaryl, wherein said heteroaryl can be substituted with one or more…Further, the R1-R4 can be variable. Overall the limited data in the Specification shows that even minor alterations in chemical structure can drastically alter IC50 for a compound and the level of permutations claimed are extremely broad relative to the similarly tested structures in of the 73 compounds actually synthesized and tested. Moreover, the “A” variable is
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in all 73 examples. Further, R6-R9 are hydrogen, fluorine, Cl, CF3, CN, or SO2Me in all of the 73 examples. The claims, however, all of RR6-R9 to include heteroaryl, CONR20R21, halo, haloalkyl, and others. Similarly, R1-R4 are hydrogen or COOH in all examples other than 58, and 62-64. In those examples, R1-R4 is hydrogen or CO-NH-SO2-Me. Thus, for 69 of the 73 examples R1, R3, and R4 are hydrogen and R2 is COOH. The “L” is an alkyl with 0-2 oxygen atoms for all 73 examples. The definition of L in the claims is vast. Not only does the data show that minor changes can alter efficacy, but the breadth of the claims for most variables fails to bear a reasonable proportion to that shown in the Specification.
Thus, in order to identify usable compounds of Formula (I-1), the skilled artisan (at minimum) would have to carry out ligand based drug design methods using the 6 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 43, 45, 52, 53, 56, 57, and 58 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for modulating ERAP1 with different degrees of in vitro potency and those conditions known to be represented by such model, is not considered enabled for prevention of diseases nor treatment of all cancers, immune disorders, inflammatory disorders, auto-inflammatory disorders, HIV, HPV, CMV, and HCV. 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. Prevention of diseases nor treatment of all cancers, inflammatory disorders, auto-inflammatory disorders, HIV, HPV, CMV, and HCV , and others are not enabled.
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.”
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 ERAP1. 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 1-73 (of claim 40, e.g.), they appear relatively similar. However, the in vitro IC50 ERAP1 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 73 compounds species encompassed by Formula (I-1) that shows activity for in vitro ERAP1 inhibitor IC50. See Specification p170. The variability in results is substantial ranging from low to high and this includes for almost identical compounds. See Example and 2, among others. Compound 1 has high IC50 and compound 2 has low IC50. This means that almost identical compounds include one with an IC50 below 250 and another with an IC50 above 1000. More specifics are not provided as to how low the low values are and how high the high values are. There are no animal models, dosages, routes of administration, or models of any disease tested. There is not a single example of a disease prevented or treated or an in vivo model in which the claimed compounds have been tested.
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 as inhibitors of ERAP1. Considering that the conditions claimed includes thousands of distinct cancers, immune conditions, autoimmune conditions, infections, viruses, and more, it is evident that the claims are broad. Yet, as discussed above, the instant Specification discloses only 73 similarly structured compound species encompassed by Formula (I-1) and the slight deviations in structure of those 73 compounds is substantial- yet such structural deviations pale in comparison to the drastic breadth of the claimed compounds. Despite the variability in efficacy and the lack of an any in vivo assay, there instant claims are directed to treating and preventing all forms of cancer, inflammatory disorders, immune conditions, infections and others. 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 disease prevented or treated or an in vivo model in which the claimed compounds have been tested.
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 ERAP1. 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-R) with respect to the disclosure since Formula (I-1) encompasses thousands of compound species, whereas the instant Specification discloses only 73 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 153 active 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 neurodegenerative conditions. To prevent and treat cancer and immune conditions in any patient population, as the instant claims are drawn to, would require undue experimentation to both develop an animal model which would reasonably correlate with all forms of neurodegenerative 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.
Conclusion
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 extension fee 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 JARED D. BARSKY whose telephone number is (571)-272-2795. The examiner can normally be reached on Monday through Friday from 8:30 to 5:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Amy L. 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