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 .
Claim Status
Claims 1-67 are pending. Claims 18-31 and 33-67 were amended in the Reply filed 10/28/2025. Claims 60-61 are withdrawn as directed to a non-elected invention. Claims 2-6, 9-14, 17, 41-45, 48-53, and 56 are withdrawn as directed to a non-elected species. Claims 1, 7-8, 15-16, 18-40, 46-47, 54-55, 57-59, and 62-67 as filed 10/28/2025 are presently considered.
Election/Restriction
Applicant's election with traverse of Group I (methods, original claims 1-58 and 61-66; renumbered as claims 1-59 and 62-67 in Reply filed 10/28/2025) and the species of Example 8 (orally administered Compound A2 at 150-450 mg twice daily in human patients having ulcerative colitis) in the reply filed on 10/28/2025 is acknowledged.
The traversal is on the grounds that “it would not be unduly burdensome to perform a search on all of the claims together” (see Reply filed 10/28/2025 at 21 at last two paragraphs). This is not found persuasive because (i) the response fails to admit that the pending claim scope is directed to (or otherwise limited to) obvious variants, (ii) the response fails to acknowledge or dispute the determination of lack of Unity of Invention identified in the Requirement mailed 4/30/2025, and (iii) the response fails to credibly or reasonably identify how examination encompassing numerous species and subgenera of methods treating different patient populations, with different structures of antagonists, at different dosages, different dosage frequencies, and different oral formulations is not burdensome, such as by identifying a single search strategy that would simultaneously search the entire prior art for the entire claim scope. Accordingly, the traversal is not persuasive. The requirement is still deemed proper and is therefore made FINAL.
The originally elected species is understood as follows: The elected species is Example 8 (see, e.g., Spec. filed 6/22/2022 at 98-101 at ¶¶[0321]-[0332]), which is understood to be a prophetic example corresponding to a planned clinical trial, wherein human patients having moderate to severe ulcerative colitis will be orally administered via tablet containing Compound A at 150 mg or 450 mg1, twice daily (BID). “Compound A” was not identified by the Applicant in the response filed 10/28/2025, but was identified by the Examiner (see Requirement mailed 4/30/2025 at footnote 2), as understood to be to be pictured and described at ¶[0198] of the Specification filed 6/22/2022, and contain SEQ ID NO: 5 linked via a DIG (diglycolic acid) linker to a second SEQ ID NO: 5 sequence:
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Applicant identified that the originally elected species read upon claims 1, 7-8, 15-16, 18-40, 46-47, 54-55, 57-59, and 62-67 as filed 10/28/2025 (see Reply filed 10/28/2025 at 22 at last three ¶¶).
Following extensive search and examination, the originally elected species has been deemed obvious and/or anticipated by the prior art, as applied below. Per MPEP § 803.02(III)(A),
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious...
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration.
Accordingly, claims 2-6, 9-14, 17, 41-45, 48-53, 56, and 60-61 are withdrawn.
Claims 60-61 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/28/2025.
Claims 2-7, 9-14, 17, 41-45, 48-53, and 56 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/28/2025.
Claims 1, 7-8, 15-16, 18-40, 46-47, 54-55, 57-59, and 62-67 as filed 10/28/2025 are presently considered.
Priority
The priority claim to Provisional 62/959,854 as filed 1/10/2020 is acknowledged.
Information Disclosure Statement
The IDS filed 9/27/2022; 1/17/2024; 3/13/2025; and 10/28/2025 are each acknowledged and presently considered.
Claim Objections
Claims 21-29 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Here, claim 18 is a multiple dependent claim, and each of claims 21-29 are also multiple dependent claims (or directly depend from a second multiple dependent claim), and are in improper form. Accordingly, claims 21-29 have not been further treated on the merits.
Claims 30-31 have been rejected as indefinite, but are understood to depend from “any one of [the previously recited] claims”, and are therefore objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Here, claims 18 and 21-29 are multiple dependent claims, and therefore claims 30-31 are in improper form. Accordingly, claims 30-31 have not been further treated on the merits.
Claims 35, 36, 37, 38, 39, 40, 46, 47, 54-55, 57-59, 62-67 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Claim 34 is a multiple dependent claim, and claims 35-40, 46-47, 54-55, 57-59, and 62-67 either recite a multiple dependent claim that depends from claim 34, or otherwise recites a claim that depends from a multiple dependent claim that depends from claim 34. Accordingly, claims 35-40, 46-47, 54-55, 57-59, and 62-67 have not been further treated on the merits.
Claim 33 is objected to because it contains redundant and superfluous language that fails to meaningfully limit the pending claim scope. Specifically, Claim 33 recites “less than 90% blood RO, less than 80% blood RO, less than 70% blood RO, less than 60% blood RO, or less than 50% blood RO” at lines 1-3. Accordingly, the claim scope is satisfied by anything that satisfies “less than 90% blood RO”, and therefore the further recitations of “less than 80% blood RO, less than 70% blood RO, less than 60% blood RO, or less than 50% blood RO” within the same claim are not further limiting, because such conditions are “less than 90% blood RO”, and anything that is “less than 90% blood RO” satisfies the claims regardless of whether or not the subsequent ranges are recited. Redundant and superfluous language should be removed to enhance claim clarity and to minimize potential confusion. Examiner suggests the following amendments: “less than 90% blood RO”.
Applicant is advised that should claims 7-8 be found allowable, claims 15-16 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Accordingly, examination on the merits has proceeded in view of the originally elected species as applied to claims 1, 7-8, 15-16, 18-20, and 32-34, as filed 10/28/2025.
Claim Rejections
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 18 and 30-34 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 18 recites “about 100.0, 112.5, 125.0….. or 500.0 mg” at lines 3-5. It is unclear if “about” modifies only “100.0” of if “about” modifies all enumerated values. The term “about” is reasonably inferred to mean ±20% of a recited value, and therefore it impacts the scope of claim 18. Accordingly, clarification is required. For purposes of examination, the term “about” is understood to modify all recited values, which means that claim 18 is understood to recite and encompass all values between “about 100.0 mg” to “about 500.0 mg”, which is the same dosage range recited at claim 1.
Claims 30-31 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: The steps corresponding to the claims upon which claims 30-31 depend, because the preamble only recites “The method of any one of claims, wherein the method….”, without actually reciting a particular claim. For purposes of examination, claims 30-31 are understood as reciting “any one of [the previously recited] claims”, and have been objected to as being in improper form under 37 CFR 1.75(c). Accordingly, further examination of claims 30-31 is precluded.
Claim 32 and claim 33 recites a functional limitation, namely “wherein the antagonist is administered at a dosage that results in a non-saturating blood receptor occupancy (%RO)” (claim 32) and “wherein the antagonist is administered at a dosage that results in less than 90% blood RO” (claim 33), which is not provided with a clear structure/function relationship commensurate in scope with the pending claims (i.e., claim 32 is not limited to any particular structure of α4β7 integrin antagonist”, and therefore is substantially broader in scope than instant claim 1). However, the language is reasonably inferred to be related to an amount of α4β7 integrin antagonist that does or does not constitute a “therapeutically effective amount” (see, e.g., Spec. filed 6/22/2022 at ¶¶[0194]-[0195]). Accordingly, the functional language is reasonably inferred to vary substantially depending upon
(i) patient population (age, body weight, general health, sex, diet, and organism),
(ii) route of administration,
(iii) “activity of the specific compound employed”,
(iv) rate of excretion,
(v) time of administration,
(vi) duration of treatment,
(vii) drugs used in combination or coincidental with the specific compound employed
(see, e.g., Spec. filed 6/22/2022 at ¶¶[0194]-[0195]). The disclosure provides limited guidance applicable to only Compound A for healthy humans (see, e.g., Spec. filed 6/22/2022 at Table 19 at 90 at ¶¶[0298]; Table 20 at 92 at ¶¶[0300]; Table 21 at 93 at ¶¶[0303], Table 22 at 94 at ¶¶[0305]). No guidance commensurate in scope with the pending claim is provided for any other α4β7 integrin antagonist for any specific patient populations, any specific route of administration, any specific “activity” levels, any specific rate of excretion, any specific times of administration, any specific durations of treatment, etc. Per MPEP § 2173.05(g), the use of functional language in a claim may fail "to provide a clear-cut indication of the scope of the subject matter embraced by the claim" and thus be indefinite. . . . For example, when claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear.” Accordingly, the functionally defined dosage renders the claim scope indefinite because (a) there is not a clear indication or well-defined boundary of what specific dosages (e.g., mg or mg/kg) are actually included or excluded from the claim scope; (b) the recitation appears to only state a problem Applicant hopes for the invention to achieve or a result they hope to obtain in the absence of clear guidance informing an artisan of how such result may be obtained for all α4β7 integrin antagonists encompassed by the pending claims; and (c) an artisan would not reasonably be able to meaningfully identify what concentrations and situations a particular α4β7 integrin antagonists (e.g., ones other than Compound A) did or did not satisfy the instant claims in the absence of additional guidance. Furthermore, extremely close prior art exists on record (see, e.g., Rejections under 35 USC 103, below). For purposes of applying prior art, claims 32-33 are reasonably inferred to be fully satisfied by Compound A, administered to patients at 100-450 mg consistent with the originally elected species and instant claim 1.
Claims 33-34 depend directly or indirectly from a rejected base claim and fail to clarify the indefiniteness of the base claim; accordingly, these claims are rejected for the reasons applicable to the base claim.
Accordingly, claims 18 and 30-34 are rejected as indefinite.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 32-34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Brief Statement of the Issue(s)
Claims 32-33 recite a functionally defined class of compounds (“α4β7 integrin antagonists”) administered at a functionally defined dosage (“wherein the antagonist is administered at a dosage that results in a non-saturating blood receptor occupancy (%RO)” at claim 32; “wherein the antagonist is administered at a dosage that results in less than 90% blood RO” at claim 33), but the originally filed disclosure does not provide requisite structure/function relationships commensurate in scope with these limitations permitting an artisan to unambiguously identify what the claim scope does or does not include.
Claim Scope
Claims 32-33 are representative of the pending claims scope. The claims are directed to methods of treating all possible “inflammatory diseases or disorder” in any “subject in need thereof” by administering (via any possible route of administration) any unspecified structure of an “α4β7 integrin antagonist” at some unknown, but functionally defined dosage (“wherein the antagonist is administered at a dosage that results in a non-saturating blood receptor occupancy (%RO)” at claim 32; “wherein the antagonist is administered at a dosage that results in less than 90% blood RO” at claim 33).
Accordingly, the claim scope appears to read upon an infinitely large genus of methods wherein potentially trillions of compounds (“α4β7 integrin antagonist” presumably encompasses peptides, DNA aptamers, AAV-vectors, enzymes, morpholinos, miRNAs, LNAs, PNA, etc. capable of acting as an antagonist in any way to an α4β7 integrin) are administered via any route (i.e., intraocular, sublingual, intravenous, topical, etc.) to any “subject in need thereof” (i.e., mammals), at any dosage frequency (i.e., BID, QD, once weekly, once monthly, etc.) at some functionally defined dosage.
Additional claim interpretations have been set forth above under 35 USC 112(b) and those discussions are incorporated herein.
It is unclear if the claim scope encompass trillions of species or perhaps only a few in view of the functional limitations set forth in the claim(s). Accordingly, the claim scope reasonably appears to be vast and highly varied.
Actual Reduction to Practice
The disclosure provides limited guidance applicable to only Compound A for healthy humans (see, e.g., Spec. filed 6/22/2022 at Table 19 at 90 at ¶¶[0298]; Table 20 at 92 at ¶¶[0300]; Table 21 at 93 at ¶¶[0303], Table 22 at 94 at ¶¶[0305]).
Zero guidance is provided for any other thioester dimer recited at or encompassed by instant claim 1, or any other art-recognized “α4β7 integrin antagonist”.
Zero guidance is provided for any route of administration other than oral routes of administration.
Zero guidance is provided for DNA aptamers, AAV-vectors, enzymes, morpholinos, miRNAs, LNAs, PNA, etc. or any other compounds capable of acting as an α4β7 integrin antagonist.
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus (see, e.g., MPEP § 2163(II)(3)(a), MPEP §2163.03(V)). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In this case, the claims encompass an essentially infinite number of methods, but limited data applicable to only one species of α4β7 integrin antagonist (i.e., Compound A) appears to have been reduced to practice or meaningfully discussed under very limited circumstances (see, e.g., Spec. filed 6/22/2022 at Table 19 at 90 at ¶¶[0298]; Table 20 at 92 at ¶¶[0300]; Table 21 at 93 at ¶¶[0303], Table 22 at 94 at ¶¶[0305]).
Although the MPEP does not define what constitutes a sufficient number of representative species, the Courts have indicated that the disclosure of two species within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618. Similarly, the disclosure of one species of the claimed invention (i.e., Compound A), and zero non-Compound A species as claimed (e.g., DNA aptamers, AAV-vectors, enzymes, morpholinos, miRNAs, LNAs, PNA, etc.) via any other route of administration (i.e., intraocular, topical, subdermal, intravenous, intravaginal, rectal, etc., etc.) does not provide sufficient disclosure to satisfy the written description requirement for the instantly claimed genus.
Identifying characteristics of the genus
In the absence of a reduction to practice of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Regarding the structures that do or do not constitute an α4β7 integrin antagonist, although the Specification identifies the function an α4β7 integrin antagonist should perform (see, e.g., Spec. filed 6/22/2022 at ¶[0056]), the originally filed disclosure does not actually identify any common structural motifs shared by all possible α4β7 integrin antagonists, which could be utilized by artisans to meaningfully identify structures capable of acting as an α4β7 integrin antagonist from structures that are not so capable. Accordingly, such language amounts to “reach-through” language attempting to capture subject matter that was not actually invented or discovered by the Applicant, but may be discovered by future inventors.
Regarding the functionally defined dosage (“wherein the antagonist is administered at a dosage that results in a non-saturating blood receptor occupancy (%RO)” at claim 32; “wherein the antagonist is administered at a dosage that results in less than 90% blood RO” at claim 33). No structure/function relationship is actually provided on record commensurate in scope with claims 32, 33, and all possible α4β7 integrin antagonists. Rather, the language is reasonably inferred to be related to an amount of α4β7 integrin antagonist that does or does not constitute a “therapeutically effective amount”, and therefore the guidance regarding what does or does not constitute a “therapeutically effective amount” is informative (see, e.g., Spec. filed 6/22/2022 at ¶¶[0194]-[0195]). Accordingly, the functional language is reasonably inferred to vary substantially depending upon
(i) patient population (age, body weight, general health, sex, diet, and organism),
(ii) route of administration,
(iii) “activity of the specific compound employed”,
(iv) rate of excretion,
(v) time of administration,
(vi) duration of treatment,
(vii) drugs used in combination or coincidental with the specific compound employed
(see, e.g., Spec. filed 6/22/2022 at ¶¶[0194]-[0195]). However, no guidance commensurate in scope with the pending claim is actually provided for all possible α4β7 integrin antagonist or even for any thioester dimer as described on record (see, e.g., instant claim 1).
The only compound discussed in detail with respect to the functional dosage is Compound A. However, even for Compound A, it is unclear what concentrations actually satisfy the functionally defined ranges at claim 33. This is because the limited data of record reflects substantial statistical variability right at the “90%” occupancy level (see, e.g., Spec. filed 6/22/2022 at Table 19 at 90 at ¶¶[0298], showing that 300 mg of Compound A yielded “83.4±7.92” Receptor Occupancy, and that 1000 mg and 1400 mg were over 90% but under 100% receptor occupancy; Table 20 at 92 at ¶¶[0300], showing that 100 mg and 300 mg, either fed or fasted, resulted in ROmax% less than 90, but that 1000 mg Fasted resulted in 91.3±2.93; Table 21 at 93 at ¶¶[0303], showing that 900 mg once daily resulted in over 90% receptor occupancy, but that 450 mg BID resulted in values that are not unambiguously less than 90% as required by the instant claim, such as 86.5±4.11 and 91.9±3.42; Table 22 at 94 at ¶¶[0305], showing that liquid formulations resulted in over 90 ROmax%, but that IR Tablet may or may not be less than 90 since the value is within the range of error - 91.9±4.56). Accordingly, even for Compound A, it is prima facie unclear if 300 mg, 900 mg, or 1000 mg are included or excluded from the pending claim scope of claim 33 reciting “less than 90% blood RO”, because such concentrations are reported as statistically indistinguishable for RO% at the 90% blood RO level (see, e.g., Spec. filed 6/22/2022 at Table 19 at 90 at ¶¶[0298], showing that 300 mg of Compound A yielded “83.4±7.92” Receptor Occupancy). Accordingly, even for Compound A, such limitations do not provide clear, unambiguous guidance regarding the conditions included or excluded from the pending claim scope.
No evidence that such limited and conflicting data can reasonably be extrapolated to any other α4β7 integrin antagonist within the scope of claims 32-34 has been found on record.
Accordingly, the record does not provide a description supporting the conclusion that Applicant possessed a functionally defined dosage range for the functionally defined genus of α4β7 integrin antagonist commensurate in scope with instant claims 32-34.
Accordingly, the functional limitations of claims 32-33 are only utilized as a vague attempt to capture unknown and undisclosed structures, sufficient to achieve some functional result that Applicant hopes and desires that the disclosed invention is able to achieve. However, the disclosure but does not meaningfully disclose an unambiguous structure/function relationship permitting an artisan to identify, a priori, which exact structures do or do not satisfy the functional limitations at issue.
Predictability in the Art
Although the level of skill in the art is high, the predictability in the art is low due to the complexity of biological systems, biochemistry, patient population variability (age, body weight, general health, sex, diet, and organism), variability of routes of administration, compound activity, duration of treatment, dosage and dosage frequency effects, and impact of drugs used in combination or coincidental with particular treatments. Specifically, an artisan would not be able to predict or identify, a priori, and in the absence of any guidance or consensus structures exactly what compounds would be capable of exhibiting α4β7 integrin antagonist activity, or dosages (and dosage frequencies and formulations for a particular antagonist) capable of resulting in a non-saturating blood receptor occupancy, such as “less than 90% blood RO” as presently claimed.
Accordingly, in the absence of sufficient structure/function teachings identifying particular compounds capable of achieving the functionally defined parameters of the pending claims, as required to practice the full scope of the claims, an artisan would not reasonably conclude that Applicant possessed the full scope of the broad and highly varied claim scope.
Conclusion
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). The courts have stated that “merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus” (see, e.g., AbbVie v. Janssen, 111 USPQ2d 1780 (Fed. Cir. 2014) at 1789). In addition, the Courts have stated
“[r]egardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
This is pertinent because, in the instant case, Applicants have claimed a broad and highly varied genus comprising an unknown number of species defined by reference to one or more functional limitations; however, the originally filed disclosure has failed to identify any common structure/function relationship sufficient to permit an artisan to identify what structures are included or excluded by the claim scope. This also means that it is prima facie unclear what structures are infringed or do not infringe upon the pending claim scope.
In conclusion, for the reasons discussed above, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Accordingly, claims 32-34 are rejected.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 7-8, 15-16, 18-20, and 32-34 are rejected under 35 U.S.C. 103 as being unpatentable over US 10059744 (Aug. 28, 2018).
Claim interpretation: The applicable claim interpretation has been set forth in preceding rejections, and those interpretations are incorporated into the instant rejection. “About” is understood to mean ±20%. Additional interpretations are set forth below.
Regarding instant claims 1, 7-8, 15-16, 18-20, 32-34, and the treatment of ulcerative colitis by orally administering dimeric α4β7 integrin antagonist structure comprising two peptides of instant SEQ ID NO: 5 dimerized by a linker moiety bound to the D-lys residues and a diglycolic acid (DIG), wherein the two peptides comprise a thioether bond between the 2-methylbenzoyl and the Pen residue: US’744 claims and discloses methods of treating subjects for inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease (see, e.g., US’744 at claims 28-30), by orally administering (see, e.g., US’744 at claims 25-27 and 31) pharmaceutical formulations comprising peptide dimer compounds comprising two peptides, each comprising the sequences of 2-methylbenzoyl-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe(4-tBu)-(β-homo-Glu)-(D-Lys)-OH (see, e.g., US’744 at claims 9, 16, and SEQ ID NOs: 270 and 223), and wherein the two peptide comprise a thioether bond between the 2-methylbenzyoyl and the Pen residues, and wherein the two peptides are linked by a linker moiety bound to the D-lys amino acids of the two peptides, and wherein the linker moiety is diglycolic acid (DIG) (see, e.g., US’744 at claims 9, 16, and SEQ ID NOs: 270 and 223, Table 5 at cols. 91-92 at SEQ ID NO 223; Table 7 at cols. 105-106 at SEQ ID NO: 223 and co. 102 at lines 2-8). Accordingly, the prior art is understood to teach and disclose methods of treating ulcerative colitis by orally administering the same compound as presently claimed. Regarding instant claims 1, 32, 34 and route of administration, US’744 claims and discloses methods of treating subjects for inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease (see, e.g., US’744 at claims 28-30), by orally administering such compounds (see, e.g., US’744 at claims 25-27 and 31; see also US’744 at col. 6 at lines 45-50, col. 74 at lines 49-66, col. 76 at lines 24-60). Regarding instant claims 1, 32, 34, and the treatment of IBD, including ulcerative colitis and Crohn’s disease, US’744 claims and discloses methods of treating subjects for inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease (see, e.g., US’744 at claims 28-30), by orally administering such compounds (see, e.g., US’744 at claims 25-27 and 31; see also US’744 at col. 75 at lines 25-40, col 78 at lines 37-45, claims 28-31).
The difference between the primary reference and the instant claims is as follows: US’744 does not claim or explicitly exemplify a method wherein the dimeric α4β7 integrin antagonist structure identified above was administered to patients, twice daily, at “about 150 mg” or “about 450 mg” (see, e.g., claim 1, 18-20, 32, and originally elected species).
Regarding instant claims 1, 7-8, 15-16, 18-20, and administration of “about 100 mg to about 500 mg”, “about 150 mg”, or “about 450 mg2” of an dimeric α4β7 integrin antagonist, US’744 teaches and discloses that the compounds and methods could be predictably practiced by administering to humans “for example, from 0.0001 to 300 mg/kg body weight daily and more usually 1 to 300 mg/kg body weight” (see, e.g., US’744 at col. 80 at lines 40-46), wherein administration could be “once daily” or “twice daily” (see, e.g., US’744 at col. 6 at lines 20-35, col. 78 at lines 13-25). The exemplified dosage range of “1 to 300 mg/kg” in “mg/kg” is reasonably inferred to overlap with the instantly claimed amounts (“mg”) because adult humans may weigh at least between 60-100 kg, which means for example, that for a 75 kg adult, a 2 mg/kg to 6 mg/kg would necessarily yield a dosage of 150 mg to 450 mg as presently claimed once daily; likewise, 4 mg/kg to 12 mg/kg, for a 75 kg adult human, would necessarily yield a suitable dosages of 150 mg to 450 mg for twice daily administration, as presently claimed. Accordingly, it is clear that the prior art range overlaps in scope with the instantly claimed dosages. Accordingly, the prior art teaches and directs artisans to use the same or overlapping dosage and dosage frequencies as instantly claimed (see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
Regarding instant claims 32-34 and RO%, claims 32-33 have been rejected as indefinite and lacking written description. For purposes of the instant rejection, the functionally-defined dosage at claims 32-34 is reasonably understood to be satisfied by “100” and “about 150 mg”, which is reasonable because such amounts were not shown on record to result in over 90% RO for Compound A on record (see, e.g., Spec. filed 6/22/2022 at Table 19 at 90 at ¶¶[0298]). Accordingly, such limitations are reasonably inferred to be fully satisfied by US’744, because US’744 teaches and discloses that the compounds and methods could be predictably practiced by administering to humans “for example, from 0.0001 to 300 mg/kg body weight daily and more usually 1 to 300 mg/kg body weight” (see, e.g., US’744 at col. 80 at lines 40-46).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason: It would have been obvious to treat IBD, such as ulcerative colitis, exactly as claimed and suggested by the prior art, namely by administering a known compound via a known administration route (oral, BID) to a known patient population (ulcerative colitis) at the concentration(s) explicitly suggested by the prior art (i.e., 1 to 300 mg/kg body weight) because the prior art provides an explicit teaching and suggestion to treat patients having the same diseases by orally administering the same compounds (see, e.g., MPEP § 2143(I)(G)), and the prior art explicitly directs artisans to use an overlapping concentration range (see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”); accordingly, the prior art elements would merely perform their art-recognized functions to predictably and expectedly yield the treatment of patients having ulcerative colitis, exactly as taught and suggested by the prior art.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well within the ordinary skill in the art to utilize a known compound in a known method for which it is taught, by a known administration route, within a known concentration range, and at a known dosage frequency, to achieve the exact treatment and outcome taught by the prior art.
Accordingly, claims 1, 7-8, 15-16, 18-20, and 32-34 are rejected.
Claims 1, 7-8, 15-16, 18-20, and 32-34 are rejected under 35 U.S.C. 103 as being unpatentable over US9714270B2 (Jul. 25, 2017).
Claim interpretation: The applicable claim interpretation has been set forth in preceding rejections, and those interpretations are incorporated into the instant rejection. “About” is understood to mean ±20%. Additional interpretations are set forth below.
The primary reference pertains to the treatment of ulcerative colitis by administering a dimeric α4β7 integrin antagonist to patients (see, e.g., US’270 at title, abs, claims 1 and 19-20).
Regarding instant claims 1, 7-8, 15-16, 18-20, 32-34, and twice daily oral administration of a compound for the treatment of ulcerative colitis, US’270 claims methods of treating a subject in need of treatment for IBD, ulcerative colitis, and Crohn’s disease by “providing” an “effective amount” of a peptide within the scope of claim 1 (see, e.g., US’270 at claims 1 and 20). The term “providing” is understood to encompass twice daily oral administration (see, e.g., US’270 at claim 20, col. 2 at lines 40-45, col. 6 at lines 37 to 45, col. 71 at line 54 to col. 72 at line 5, col. 73 at lines 29-31, col. 75 at lines 17-30). Regarding instant claims 1, 7-8, 15-16, 18-20, 32-34, and the treatment of ulcerative colitis by orally administering dimeric α4β7 integrin antagonist structure comprising two peptides of instant SEQ ID NO: 5 dimerized by a linker moiety bound to the D-lys residues and a diglycolic acid (DIG), wherein the two peptides comprise a thioether bond between the 2-methylbenzoyl and the Pen residue: US’270 claims methods of treating a subject in need of treatment for ulcerative colitis (see, e.g., US’270 at claims 1 and 20), by administering compounds of claim 1 (see id), which includes dimeric α4β7 integrin antagonist peptides linked by a diglycolic acid (DIG) (see, e.g., US’270 at claims 1, 5, 10-19), which would be readily understood to include exemplified embodiments such as SEQ ID NO: 223 (see, e.g., US’270 at Table 5 at Col. 87-88, showing illustrative thioether dimer SEQ ID NO: 223; see also US’270 at US’270 at Table 7 at col. 101-102, showing “*”, which denotes highest assayed potency of “<25 nM” as explained at col. 96 at lines 20-28, for both Cell-Adhesion of α4β7 and PBMC IC50), wherein SEQ ID NO: 223 is understood to be a dimer comprising the sequence of 2-methylbenzoyl-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe(4-tBu)-(β-homo-Glu)-(D-Lys)-OH (see, e.g., US’270 at Table 5 at col. 87-88, showing structure of SEQ ID NO: 223), wherein the dimer is formed by a linkage between each D-Lys residue via a diglycolic acid (DIG) linker, and wherein the two peptides comprise a thioether bond between the 2-methylbenzoyl and the Pen residue (see, e.g., US’270 at Table 5 at col. 87-88, col. 319-322 at description of SEQ ID NO: 223 at field codes <210> to <400>; see also US’270 at exemplifications at Figs. 1-2 and 5, exemplifying general construction and structures of dimers conjugated via a DIG linker and having thioether bonds between the 2-methylbenzoyl and Pen residues).
The difference between the primary reference and the instant claims is as follows: the primary reference does not claim or explicitly exemplify a method wherein the dimeric α4β7 integrin antagonist structure identified above was administered at “about 150 mg” or “about 450 mg” (see, e.g., claim 1, 18-20, 32, and originally elected species).
Regarding instant claims 1, 7-8, 15-16, 18-19, and administration of “about 100 mg to about 500 mg”, or “about 150 mg” of an dimeric α4β7 integrin antagonist, US’270 claims methods of treating a subject in need of treatment for IBD, ulcerative colitis, and Crohn’s disease by “providing” an “effective amount” of a peptide within the scope of claim 1 (see, e.g., US’270 at claims 1 and 20). The term “effective amount” is understood to include at least the exemplified dosage range of “1 to 300 mg/kg body weight” (see, e.g., US’270 at col. 77 at lines 44-50). The exemplified dosage range of “1 to 300 mg/kg” in “mg/kg” is reasonably inferred to overlap with the instantly claimed amounts (“mg”) because adult humans may weigh at least between 60-100 kg, which means for example, that for a 75 kg adult, a 2 mg/kg to 6 mg/kg would necessarily yield a dosage of 150 mg to 450 mg as presently claimed once daily; likewise, 4 mg/kg to 12 mg/kg, for a 75 kg adult human, would necessarily yield a suitable dosages of 150 mg to 450 mg for twice daily administration, as presently claimed. Accordingly, it is clear that the prior art range overlaps in scope with the instantly claimed dosages (see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
Regarding instant claims 32-34 and RO%, claims 32-33 have been rejected as indefinite and lacking written description. For purposes of the instant rejection, the functionally-defined dosage at claims 32-34 is reasonably understood to be satisfied by “100” and “about 150 mg”, which is reasonable because such amounts were not shown on record to result in over 90% RO for Compound A on record (see, e.g., Spec. filed 6/22/2022 at Table 19 at 90 at ¶¶[0298]). Accordingly, such limitations are reasonably inferred to be fully satisfied by US’270, which claims methods of treating a subject in need of treatment for IBD, ulcerative colitis, and Crohn’s disease by “providing” an “effective amount” of a peptide within the scope of claim 1 (see, e.g., US’270 at claims 1 and 20). The term “providing” is understood to encompass twice daily oral administration (see, e.g., US’270 at claim 20, col. 2 at lines 40-45, col. 6 at lines 37 to 45, col. 71 at line 54 to col. 72 at line 5, col. 73 at lines 29-31, col. 75 at lines 17-30). The term “effective amount” is understood to include at least the exemplified dosage range of “1 to 300 mg/kg body weight” (see, e.g., US’270 at col. 77 at lines 44-50) (see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason: It would have been obvious to treat IBD, such as ulcerative colitis, exactly as claimed and suggested by the prior art, namely by administering a known compound via a known administration route (oral, BID) to a known patient population (ulcerative colitis) at the concentration(s) explicitly suggested by the prior art (i.e., 1 to 300 mg/kg body weight) because the prior art provides an explicit teaching and suggestion to treat patients having the same diseases by orally administering the same compounds (see, e.g., MPEP § 2143(I)(G)), and the prior art explicitly directs artisans to use an overlapping concentration range (see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”); accordingly, the prior art elements would merely perform their art-recognized functions to predictably and expectedly yield the treatment of patients having ulcerative colitis, exactly as taught and suggested by the prior art.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well within the ordinary skill in the art to utilize a known compound in a known method for which it is taught, by a known administration route, within a known concentration range, and at a known dosage frequency, to achieve the exact treatment and outcome taught by the prior art.
Accordingly, claims 1, 7-8, 15-16, 18-20, and 32-34 are rejected.
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, 7-8, 15-16, 18-20, and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 17-20 of U.S. Patent No. 9714270B2 (Jul. 25, 2017).
Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims 1, 7-8, 15-16, 18-20, and 32-34 are directed to methods of treating subjects for IBD (e.g., ulcerative colitis and Crohn’s disease) by orally administering a dimeric α4β7 integrin antagonist at “about 150 mg” or “about 450 mg” (see, e.g., instant claims 1, 7-8, 15-16, 18-20, and 32-34). However, US’270 claims methods of treating a subject in need of treatment for IBD, ulcerative colitis, and Crohn’s disease by “providing” an “effective amount” of a peptide within the scope of claim 1 (see, e.g., US’270 at claims 1, 5, 17-20).
The difference between the issued claims and the instant claims are as follows: The issued claims do not explicitly (i) recite oral administration, once or twice daily, using 150 mg or 450 mg dosages, as required by claims 1, 18-20 and 32-34 or (ii) the dimeric α4β7 integrin antagonists specifically set forth at instant claims 1, 7-8, and 15-16.
Per MPEP § 804(II)(B)(1), it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim (see, e.g., MPEP § 804(II)(B)(1)). Here, claim 20 recites “providing”, which is understood and interpreted to fully encompass twice daily oral administration (see, e.g., US’270 at claim 20, col. 2 at lines 40-45, col. 6 at lines 37 to 45, col. 71 at line 54 to col. 72 at line 5, col. 73 at lines 29-31, col. 75 at lines 17-30).
Per MPEP § 804(II)(B)(1), it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim (see, e.g., MPEP § 804(II)(B)(1)). Here, claim 20 recites and requires providing an “effective amount” (see, e.g., US’270 at claim 20). The phrase “effective amount” is understood to include at least the exemplified dosage range of “1 to 300 mg/kg body weight” (see, e.g., US’270 at col. 80 at lines 40-46). The exemplified dosage range of “1 to 300 mg/kg” in “mg/kg” is reasonably inferred to overlap with the instantly claimed amounts (“mg”) because adult humans may weigh at least between 60-100 kg, which means for example, that for a 75 kg adult, a 2 mg/kg to 6 mg/kg would necessarily yield a dosage of 150 mg to 450 mg as presently claimed once daily; likewise, 4 mg/kg to 12 mg/kg, for a 75 kg adult human, would necessarily yield a suitable dosages of 150 mg to 450 mg for twice daily administration, as presently claimed. Accordingly, it is clear that the prior art range overlaps in scope with the instantly claimed dosages (see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
Regarding instant claims 1, the dimeric α4β7 integrin antagonists, claims 1, 5, 17-19 of US’270 define a genus of compounds that overlap in scope with the instant claims 1, 7-8, and 15-16 as explained below. Per MPEP § 804(II)(B)(1), it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim and to identify obvious variants of a claimed invention (see, e.g., MPEP § 804(II)(B)(1)). Here, US’270 at claim 20 recites methods of administering any compounds within the scope of claim 1 (see, e.g., US’270 at claims 1 and 20), which would be readily understood to include at least dimeric α4β7 integrin antagonist peptides linked by a diglycolic acid (DIG) (see, e.g., US’270 at claims 1, 5, 10-19), including the exemplified embodiments such as SEQ ID NO: 223 (see, e.g., US’270 at Table 5 at Col. 87-88, showing illustrative thioether dimer SEQ ID NO: 223; see also US’270 at US’270 at Table 7 at col. 101-102, showing “*”, which denotes highest assayed potency of “<25 nM” as explained at col. 96 at lines 20-28, for both Cell-Adhesion of α4β7 and PBMC IC50), wherein SEQ ID NO: 223 is understood to be a dimer comprising the sequence of 2-methylbenzoyl-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe(4-tBu)-(β-homo-Glu)-(D-Lys)-OH (see, e.g., US’270 at Table 5 at col. 87-88, showing structure of SEQ ID NO: 223), wherein the dimer is formed by a linkage between each D-Lys residue via a diglycolic acid (DIG) linker, and wherein the two peptides comprise a thioether bond between the 2-methylbenzoyl and the Pen residue (see, e.g., US’270 at Table 5 at col. 87-88, col. 319-322 at description of SEQ ID NO: 223 at field codes <210> to <400>; see also US’270 at exemplifications at Figs. 1-2 and 5, exemplifying general construction and structures of dimers conjugated via a DIG linker and having thioether bonds between the 2-methylbenzoyl and Pen residues). The structure corresponding to SEQ ID NO: 223 described above is identical to the structure of the originally elected species.
Regarding instant claims 32-34 and RO%, claims 32-33 have been rejected as indefinite and lacking written description. For purposes of the instant rejection, the functionally-defined dosage at claims 32-34 is reasonably understood to be satisfied by “100 mg” and “about 150 mg”, which is reasonable because such amounts were not shown on record to result in over 90% RO for Compound A on record (see, e.g., Spec. filed 6/22/2022 at Table 19 at 90 at ¶¶[0298]). Accordingly, such limitations are reasonably inferred to be fully satisfied by the issued claims of US’270 as explained above, because claim 20 of US’270 recites and requires providing an “effective amount” (see, e.g., US’270 at claim 20). The phrase “effective amount” is understood to include at least the exemplified dosage range of “1 to 300 mg/kg body weight” (see, e.g., US’270 at col. 77 at lines 40-50; see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a substantially and materially overlapping method of treating IBD, wherein both claim sets read upon species of administering the same compounds to the same patient population at the same (or overlapping) dosage, via the same (or obvious) route of administration to achieve the same predicted and expected outcomes (see, e.g., MPEP § 804(II)(B)(3)(B)). Accordingly, the present claims are understood to be directed to obvious variants of the issued claims because it is well-within the ordinary skill in the art to practice a known, issued, and claimed method using known compounds at known concentrations, wherein administration is via known routes (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(I)(G), 2144.05(I).
As issued claims in a U.S. patent, the reference claims are presumed to satisfy all statutory requirements in the absence of evidence to the contrary. Accordingly, the instant claims are directed to an obvious, claimed variant of the patent claims, namely the claims are directed to a subgenus of methods as set forth in the issued claims. Therefore, the instant claims substantially overlap in scope with the issued claims and unambiguously encompass obvious variants of the issued claims.
As required at (C) of MPEP § 804(II), the rejection is not prohibited by 35 U.S.C. 121.
As noted at MPEP § 804(II)(B)(4), the reference patent and the instant Application are understood to require only a one-way test for distinctiveness.
Accordingly, instant claims 1, 7-8, 15-16, 18-20, and 32-34 are rejected.
Claims 1, 7-8, 15-16, 18-20, and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 10059744 (Aug. 28, 2018)
Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims 1, 7-8, 15-16, 18-20, and 32-34 are directed to methods of treating subjects for IBD (e.g., ulcerative colitis and Crohn’s disease) by orally administering a dimeric α4β7 integrin antagonist at “about 150 mg” or “about 450 mg” (see, e.g., instant claims 1, 7-8, 15-16, 18-20, and 32-34). However, US’744 claims methods of treating a subject in need of treatment for IBD, ulcerative colitis, and Crohn’s disease by orally administering an “effective amount” of a dimeric peptide α4β7 integrin antagonist (see, e.g., US’744 at claims 1, 9, 19, 28-31), wherein the dimeric peptide α4β7 integrin antagonist is a dimer formed from SEQ ID NO: 223 (i.e., 2-methylbenzoyl-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe(4-tBu)-(β-homo-Glu)-(D-Lys)-OH), wherein the two peptides are linked by a linker moiety bound to the D-lys amino acids of the two peptides, wherein the linker is diglycolic acid (DIG), and wherein each peptide comprises a thioether bond between the 2-methylbenzyoyl and the Pen residues (see, e.g., US’744 at claims 1-23; see esp. claim 23 referring to SEQ ID NO: 223). In sum, the issued claims of US’744 claim methods of treating the same diseases by orally administering the same dimeric α4β7 integrin antagonist present in the originally elected species.
The difference between the issued claims and the instant claims are as follows: The issued claims do not explicitly recite once or twice daily administration using 150 mg or 450 mg dosages.
Per MPEP § 804(II)(B)(1), it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim (see, e.g., MPEP § 804(II)(B)(1)). Per MPEP § 804(II)(B)(1), it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim (see, e.g., MPEP § 804(II)(B)(1)). Here, claim 28 recites “providing”, which is understood and interpreted to fully encompass twice daily oral administration (see, e.g., US’744 at claim 28, col. 6 at lines 20-50, col. 74 at lines 60-66, col. 78 at lines 15-25).
Per MPEP § 804(II)(B)(1), it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim (see, e.g., MPEP § 804(II)(B)(1)). Here, claim 28 recites and requires providing an “effective amount” (see, e.g., US’744 at claim 28). The phrase “effective amount” is understood to include at least the exemplified dosage range of “1 to 300 mg/kg body weight” (see, e.g., US’744 at col. 80 at lines 40-46). The exemplified dosage range of “1 to 300 mg/kg” in “mg/kg” is reasonably inferred to overlap with the instantly claimed amounts (“mg”) because adult humans may weigh at least between 60-100 kg, which means for example, that for a 75 kg adult, a 2 mg/kg to 6 mg/kg would necessarily yield a dosage of 150 mg to 450 mg as presently claimed once daily; likewise, 4 mg/kg to 12 mg/kg, for a 75 kg adult human, would necessarily yield a suitable dosages of 150 mg to 450 mg for twice daily administration, as presently claimed. Accordingly, it is clear that the prior art range overlaps in scope with the instantly claimed dosages (see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
Regarding instant claims 32-34 and RO%, claims 32-33 have been rejected as indefinite and lacking written description. For purposes of the instant rejection, the functionally-defined dosage at claims 32-34 is reasonably understood to be satisfied by “100 mg” and “about 150 mg”, which is reasonable because such amounts were not shown on record to result in over 90% RO for Compound A on record (see, e.g., Spec. filed 6/22/2022 at Table 19 at 90 at ¶¶[0298]). Accordingly, such limitations are reasonably inferred to be fully satisfied by the issued claims of the primary reference as explained above, because the issued claims recite and require providing an “effective amount”. The phrase “effective amount” is understood to include at least the exemplified dosage range of “1 to 300 mg/kg body weight” as discussed above (see, e.g., US’744 at col. 80 at lines 40-46; see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a substantially and materially overlapping method of treating IBD, wherein both claim sets read upon species of administering the same compounds to the same patient population at the same (or overlapping) dosage, via the same (or obvious) route of administration to achieve the same predicted and expected outcomes (see, e.g., MPEP § 804(II)(B)(3)(B)). Accordingly, the present claims are understood to be directed to obvious variants of the issued claims because it is well-within the ordinary skill in the art to practice a known, issued, and claimed method using known compounds at known concentrations, wherein administration is via known routes (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(I)(G), 2144.05(I).
As issued claims in a U.S. patent, the reference claims are presumed to satisfy all statutory requirements in the absence of evidence to the contrary. Accordingly, the instant claims are directed to an obvious, claimed variant of the patent claims, namely the claims are directed to a subgenus of methods as set forth in the issued claims. Therefore, the instant claims substantially overlap in scope with the issued claims and unambiguously encompass obvious variants of the issued claims.
As required at (C) of MPEP § 804(II), the rejection is not prohibited by 35 U.S.C. 121.
As noted at MPEP § 804(II)(B)(4), the reference patent and the instant Application are understood to require only a one-way test for distinctiveness.
Accordingly, instant claims 1, 7-8, 15-16, 18-20, and 32-34 are rejected.
Claims 1, 7-8, 15-16, 18-20, and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,840,581 (Dec. 12, 2023).
Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims 1, 7-8, 15-16, 18-20, and 32-34 are directed to methods of treating subjects for IBD (e.g., ulcerative colitis and Crohn’s disease) by orally administering a dimeric α4β7 integrin antagonist at “about 150 mg” or “about 450 mg” (see, e.g., instant claims 1, 7-8, 15-16, 18-20, and 32-34). However, US’581 claims methods of treating a subject in need of treatment for IBD, ulcerative colitis, and Crohn’s disease (see US’581 at claims 1 and 9-16) by “providing” or orally administering (see US’581 at claims 1, 7, 17) an “effective amount” of a dimeric peptide α4β7 integrin antagonist (see, e.g., US’581 at claims 1), wherein the dimeric peptide α4β7 integrin antagonist is a dimer formed from SEQ ID NO: 223 (i.e., 2-methylbenzoyl-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe(4-tBu)-(β-homo-Glu)-(D-Lys)-OH), wherein the two peptides are linked by a linker moiety bound to the D-lys amino acids of the two peptides, wherein the linker is diglycolic acid (DIG), and wherein each peptide comprises a thioether bond between the 2-methylbenzyoyl and the Pen residues (see, e.g., US’581 at claims 1-5; see esp. claims 4-5 referring to SEQ ID NO: 223). In sum, the issued claims of US’581 claim methods of treating the same diseases by “providing” or orally administering the same dimeric α4β7 integrin antagonist present in the originally elected species.
The difference between the issued claims and the instant claims are as follows: The issued claims do not explicitly require oral administration of SEQ ID NO: 223, once or twice daily, using 150 mg or 450 mg dosages, as required by instant claims 1, 18-20 and 32-34.
Per MPEP § 804(II)(B)(1), it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim (see, e.g., MPEP § 804(II)(B)(1)). Here, claim 1 recites “providing”, which is understood and interpreted to fully encompass twice daily oral administration (see, e.g., US’581 at col. 6 at lines 5-60, col. 76 at lines 35-46, col. 80 at lines 50-55).
Per MPEP § 804(II)(B)(1), it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim (see, e.g., MPEP § 804(II)(B)(1)). Here, claim 20 recites and requires providing an “effective amount” (see, e.g., US’581 at claim 1). The phrase “effective amount” is understood to include at least the exemplified dosage range of “1 to 300 mg/kg body weight” (see, e.g., US’581 at col. 80 at lines 50-55).The exemplified dosage range of “1 to 300 mg/kg” in “mg/kg” is reasonably inferred to overlap with the instantly claimed amounts (“mg”) because adult humans may weigh at least between 60-100 kg, which means for example, that for a 75 kg adult, a 2 mg/kg to 6 mg/kg would necessarily yield a dosage of 150 mg to 450 mg as presently claimed once daily; likewise, 4 mg/kg to 12 mg/kg, for a 75 kg adult human, would necessarily yield a suitable dosages of 150 mg to 450 mg for twice daily administration, as presently claimed. Accordingly, it is clear that the prior art range overlaps in scope with the instantly claimed dosages (see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
Regarding instant claims 32-34 and RO%, claims 32-33 have been rejected as indefinite and lacking written description. For purposes of the instant rejection, the functionally-defined dosage at claims 32-34 is reasonably understood to be satisfied by “100 mg” and “about 150 mg”, which is reasonable because such amounts were not shown on record to result in over 90% RO for Compound A on record (see, e.g., Spec. filed 6/22/2022 at Table 19 at 90 at ¶¶[0298]). Accordingly, such limitations are reasonably inferred to be fully satisfied by the issued claims of the primary reference as explained above, because the issued claims recite and require providing an “effective amount”. The phrase “effective amount” is understood to include at least the exemplified dosage range of “1 to 300 mg/kg body weight” as discussed above (see, e.g., US’581 at col. 80 at lines 50-55; see, e.g., MPEP § 2144.05(I), explaining that “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a substantially and materially overlapping method of treating IBD, wherein both claim sets read upon species of administering the same compounds to the same patient population at the same (or overlapping) dosage, via the same (or obvious) route of administration to achieve the same predicted and expected outcomes (see, e.g., MPEP § 804(II)(B)(3)(B)). Accordingly, the present claims are understood to be directed to obvious variants of the issued claims because it is well-within the ordinary skill in the art to practice a known, issued, and claimed method using known compounds at known concentrations, wherein administration is via known routes (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(I)(G), 2144.05(I).
As issued claims in a U.S. patent, the reference claims are presumed to satisfy all statutory requirements in the absence of evidence to the contrary. Accordingly, the instant claims are directed to an obvious, claimed variant of the patent claims, namely the claims are directed to a subgenus of methods as set forth in the issued claims. Therefore, the instant claims substantially overlap in scope with the issued claims and unambiguously encompass obvious variants of the issued claims.
As required at (C) of MPEP § 804(II), the rejection is not prohibited by 35 U.S.C. 121.
As noted at MPEP § 804(II)(B)(4), the reference patent and the instant Application are understood to require only a one-way test for distinctiveness.
Accordingly, instant claims 1, 7-8, 15-16, 18-20, and 32-34 are rejected.
Claims 1, 7-8, 15-16, 18-20, and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 10,626,146 (Apr. 21, 2020).
Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims 1, 7-8, 15-16, 18-20, and 32-34 are directed to methods of treating subjects for IBD (e.g., ulcerative colitis and Crohn’s disease) by orally administering a dimeric α4β7 integrin antagonist at “about 150 mg” or “about 450 mg” (see, e.g., instant claims 1, 7-8, 15-16, 18-20, and 32-34). Here, the claims of US’146 recite pharmaceutical formulations comprising the same or overlapping compounds (see, e.g., US’146 at claims 1-22), including the originally elected species (see, e.g., US’146 at claims 18-20). Although the claims do not recite a method of orally administering such compounds, twice daily, at 150 or 450 mg, to treat IBD (i.e., ulcerative colitis), in view of Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010), the Examiner is allowed to look at the specification of the patent to determine the use of the claimed compound. Here, the specification discloses that the compound(s) may be administered to patients to treat IBD and ulcerative colitis (see, e.g., US’146 at col. 2 at lines 5-15, col. 6 at lines 10-15), via oral administration (see, e.g., US’146 at col. 6 at lines 40-45), twice daily (see, e.g., US’146 at col. 6 at lines 15-26), at 1-300 mg/kg (see, e.g., US’146 at col. 80 at lines 42-46). Accordingly, in view of Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010), the instantly claimed method is not patentably distinct over the claimed compound of US’146.
Claims 1, 7-8, 15-16, 18-20, and 32-34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 18/139,254 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets appear to be directed to the treatment of IBD in a subject (compare instant claims with App’254 at claims 1 and 16-19), by orally administering the same compound (compare instant claims 1, 7-8, 15-16, and elected species with App’254 at claims 1, 10, and structure “(I)”), at the same or overlapping concentration (compare instant claims 1 and 18-20 with App’254 at claims 3-5, identifying that the ranges at claim 1 encompass 50-1000 mg), twice daily (compare instant claims with App’254 at claim 15). Accordingly, although drafted differently, the copending claim sets are not patentably distinct from each other because they appear to claim the same or substantially identical subject matter.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 7-8, 15-16, 18-20, and 32-34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-44 of copending Application No. 19/303,188 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets appear to be directed to the treatment of IBD in a subject (compare instant claims with App’188 at claims 1, 26-38), by orally administering (compare instant claims with App’188 at claims 1, 34-44) the same compound (compare instant claims 1, 7-8, 15-16, and elected species with App’188 at claims 1-30, SEQ ID NO: 223), at the same or overlapping concentration (compare instant claims 1 and 18-20 with App’188 at claim 34, reciting an “effective amount”, which is exemplified as meaning at least 1 to 300 mg/kg at ¶[00740] of the disclosure of App’188), twice daily (compare instant claims with App’188 at claim 41). Accordingly, although drafted differently, the copending claim sets are not patentably distinct from each other because they appear to claim the same or substantially identical subject matter.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 Note that this is “mg”, not “mg/kg”.
2 Note that claims 1 and 18-20 refer to a range of “mg” only, rather than “mg/kg”.