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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/04/2026 has been entered.
Claim Status
Claims 88-91, 94, 98-100, 102-103, 105, 107-108, 110, 117-119 are pending. Claims 92 and 111 were canceled; claims 88, 94, 102, 105, 110, and 117-119 were amended; and no new claims were added in the Reply filed 3/04/2026. Claim 100 remains withdrawn. Claims 88-91, 94, 98-99, 102-103, 105, 107-108, 110, and 117-119 are presently considered.
Election/Restrictions
Applicant’s election without traverse of the species in the reply filed on 8/01/2024 was previously acknowledged.
As noted previously, Applicant did not elect a single Example, but rather a subgenus of patentably indistinct species comprising all Examples of record because “all examples are based off one protocol” (see, e.g., Reply filed 8/01/2024 at 7-8). Accordingly, the parameters tested within such examples are understood to be obvious variants of one another, and this understanding has not been challenged on any objective legal basis on record to date.
The originally elected, narrow grouping of patentably indistinct species is understood to be encompass a method of administering Avexitide for at least 28 days, wherein the route of administration is subcutaneous injection at 30 mg SC formulation twice daily (BID) for 14 days, 60 mg once daily (QD) injections for 14 days of active dosing (see, e.g., Reply filed 8/01/2024 at 7-8), wherein the Avexitide injection consists of 30 mg/mL in a sodium acetate buffer containing mannitol as a tonicity modifier, in 1 mL of solution (see, e.g., Specification filed 4/14/2021 at ¶[0193]). Applicant explicitly identified that the originally elected species is patients who have had gastric bypass surgery (see, e.g., Reply filed 8/01/2024 at 7-8).
Following extensive search and examination, the originally elected subgenus of patentably indistinct species was deemed anticipated and/or obvious in view of 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.
In view of the amendments filed 3/04/2026, the next relevant question is whether or not the originally elected subgenus continues to read upon the amended claim scope. Applicant fails to identify whether or not the amendments exclude the originally elected subgenus, and amended claim 88 now recites a functional limitation (i.e., replacing the objective range of “at least 14 days” with the functionally defined/determined duration of “a time sufficient to reduce diurnal percent time during which the subject’s glucose level is less than 70 mg/dL as measured by CGM by about 4% to about 26%”). Upon review, the functionally defined duration is understood to continue reading upon the amended claim scope, including treatment durations of the previously examined claims (i.e., at least 14 days) and originally elected subgenus of species (see, e.g., Spec. filed 4/14/2021 at ¶¶[0187], [0190], [0197], [0202], [0204], [0210]-[0211], [0214], [0242]-[0243] at Tables 8-9, [0278], all referring to a 14-day treatment plan).
Amended claim 100 remains 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. Election was made without traverse in the reply filed on 8/01/2024.
Claims 88-91, 94, 98-99, 102-103, 105, 107-108, 110 and 117-119 are presently considered.
Priority
The priority claim to Provisional 62/745,915 (filed 10/15/2018) is acknowledged.
Information Disclosure Statement
The IDS filed 11/04/2025; 3/04/2026; and 3/27/2026 are acknowledged and presently considered.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Amended claim 88 is representative of the pending claim scope and presently recites:
88. (Currently Amended) A method of reducing, in a human subject diagnosed with post-bariatric hypoglycemia (PBH), the diurnal percent time during which the subject’s glucose level is less than 70 mg/dL as measured by continuous glucose monitor (CGM), the method comprising subcutaneously administering to the human subject at least 60 mg of avexitide once daily for a time sufficient to reduce in the human subject the mean percent time spent in hypoglycemia by about 4% to about 26%.
Accordingly, the claimed invention is understood to be a treatment method characterized by the following parameters:
Patient population: Amended claim 88 is understood to identify the applicable patient population as “human subjects” that have been “diagnosed with post-bariatric hypoglycemia (PBH)” (see amended claim 88).
Administered compound(s): Amended claim 88 explicitly identifies that the compound administered is avexitide (see amended claim 88). Avexitide is identified as “exendin(9-39)” and is understood to be a 31-mer amino acid peptide comprising residues 9-39 of the GLP-1 receptor agonist exendin-4 and is an art-recognized GLP-1 receptor antagonist with inverse agonist properties, which has a sequence as set forth at instant SEQ ID NO: 11 (see, e.g., Spec. filed 4/14/2021 at ¶[0030]; see also CAS No. 133514-43-9).
Administration route: Amended claim 88 explicitly identifies that the compound is administered subcutaneously (see amended claim 88).
Dosage and Dosage frequency: Amended claim 88 explicitly identifies that avexitide is administered once daily at a concentration of “at least 60 mg” (see amended claim 88). In view of the original election, this is understood to be equivalent to other forms of administering at least 60 mg per day disclosed in the Examples of record (e.g., BID).
Treatment duration: Amended claim 88 has replaced the objective duration of “at least 14 days” with the functionally defined duration of “a time sufficient to reduce diurnal percent time during which the subject’s glucose level is less than 70 mg/dL as measured by CGM by about 4% to about 26%”). However, upon review, this functionally defined time range is understood to include the treatment durations of previously examined claims and the originally elected subgenus of species (i.e., at least 14 days). This is reasonable in view of the exemplified embodiments of record (see, e.g., Spec. filed 4/14/2021 at ¶¶[0187], [0190], [0197], [0202], [0204], [0210]-[0211], [0214], [0242]-[0243] at Tables 8-9, [0278], all referring to a 14-day treatment plan). Notably, claim 91 identifies an objective duration, namely “30 days or less”, which ostensibly reads upon 1 day, unless 1 day is excluded by the functionally defined duration of amended claim 88.
Monitoring/Assessment of Treatment: Amended claim 88 requires that a subject’s glucose level is measured by a continuous glucose monitor (CGM) (see amended claim 88).
Additional claim interpretations are discussed below.
Preamble: The amended preamble phrase
“of reducing, in a human subject diagnosed with post-bariatric hypoglycemia (PBH), the diurnal percent time during which the subject’s glucose level is less than 70 mg/dL as measured by continuous glucose monitor (CGM)”
is interpreted consistent with MPEP § 2111.02, § 2111.04(I), and § 2111.02(II). Specifically, MPEP § 2111.02 recites that preamble determinations are made on “a case-by-case basis” and that “there is no litmus test defining when a preamble limits the scope of a claim”, but rather “[A] claim preamble has the import that the claim as a whole suggests for it” (see, e.g., MPEP § 2111.02). Here, the preamble is understood to define the patient population (i.e., human subjects diagnosed with post-bariatric hypoglycemia (PBH)”, which limits the scope of the claim by objectively limiting the patient population (see, e.g., MPEP § 2111.02(I)). However, the preamble also recites a purpose and intended use (i.e., “of reducing . . . the diurnal percent time during which the subject’s glucose level is less than 70 mg/dL as measured by continuous glucose monitor (CGM)”), which is understood to necessarily and inherently be satisfied by any prior art method wherein the same patient population (i.e., humans diagnosed with PBH) are administered the same compound (i.e., Avexitide) at the same dosage (i.e., 60 mg), the same dosage frequency (i.e., once daily), the same administration route (i.e., subcutaneous), for the same or overlapping total duration (i.e., at least 14 days). This is reasonable because the intended use statements do not pertain to structure/function limitations of record, and therefore such recitations are understood to necessarily and inherently be satisfied by the positively recited steps set forth in the body of claim 88. If this is incorrect, Applicant should clearly identify what exact intended result amounts to a limitation that would not be inherently and necessarily satisfied, and fully enabled, by prior art treating humans diagnosed with PBH by subcutaneously administering 60 mg of Avexitide, once daily, for at least 14 days. In the absence of clear identification of a patentable difference, the performance of the same, positively recited method steps would be readily understood to result in the same outcomes, unless the full scope of the claims is not enabled. For purposes of the instant action, the claims are currently presumed fully enabled.
At claims 89-90 and 98, “Buffered liquid formulation” is understood to include at least an Avexitide injection consists of 30 mg/mL in a sodium acetate buffer containing mannitol as a tonicity modifier, in 1 mL solution (see, e.g., Specification filed 4/14/2021 at ¶[0193]), as present in the originally elected species (see, e.g., Reply filed 8/01/2024 at 7-8).
Amended claims 117-119 depend from claim 88, and ostensibly differ from claim 88 only by recitation of a “wherein” clause. The “wherein” clause ostensibly limits the treatment duration to a time sufficient to achieve a functional outcome:
At claim 117, “avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 70 mg/dL as measured by CGM by up to about 26%”;
At claim 118, “avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 55 mg/dL as measured by CGM by up to about 24%”
At claim 119, “avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 40 mg/dL as measured by CGM by up to about 4%”
The term “about” is not defined on record, but has previously been interpreted as “within 20 percent” (see, e.g., Action mailed 11/05/2025 at 6-7 at bridging ¶). “Up to” is understood to include zero (i.e., “up to about X%” reasonably includes 0-X%). The functionally defined durations do not correspond to any structure/function relationship of record. For purposes of applying prior art under 35 USC 102 or 103, the wherein clauses of claims 117-119 are presumed fully satisfied by prior art teaching or rendering obvious the treatment of humans diagnosed with PBH by subcutaneously administering 60 mg of Avexitide, once daily, for at least 14 days, which is reasonable in view of the originally elected species and instant disclosure (see, e.g., Spec. filed 4/14/2021 at ¶¶[0187], [0190], [0197], [0202], [0204], [0210]-[0211], [0214], [0242]-[0243] at Tables 8-9, [0278], all referring to a 14-day treatment plan).
Amended claims 105, 107, 108, 110, and 111 are understood to recite a “wherein” clause expressing the intended and expected results that would necessarily and inherently occur upon the successful completion of the positively recited method steps set forth in the body of amended claim 88, because these claims do not recite nor require additional steps to be performed (see, e.g., MPEP § 2111.04(I)). Accordingly, for purposes of applying prior art, the intended or expected results of claims 105, 107, 108, 110, and 111 are understood to be fully satisfied by any prior art methodology wherein teaching or rendering obvious the treatment of humans diagnosed with PBH by subcutaneously administering 60 mg of Avexitide, once daily, for at least 14 days, which is reasonable in view of the originally elected species and instant disclosure (see, e.g., Spec. filed 4/14/2021 at ¶¶[0187], [0190], [0197], [0202], [0204], [0210]-[0211], [0214], [0242]-[0243] at Tables 8-9, [0278]).
Additional claim interpretations are set forth below.
Withdrawn Claim Rejections
All prior art rejections are withdrawn in view of the extensive amendments filed 3/04/2026. The amendments have necessitated new or revised rejections, which are set forth below. This action is non-final.
New, Maintained or Revised Claim Rejections Necessitated by Applicant Amendment
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 88-91, 94, 98-99, 102-103, 105, 107-108, 110, and 117-119 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.
Amended claims 88, 117, 118, and 119 each recites a method of treatment, wherein the total duration of the treatment is functionally defined by recitation of results and outcomes Applicant hopes and desires to acheive:
At claim 88, “for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 70 mg/dL as measured by CGM by about 4% to about 26%”;
At claim 117, “avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 70 mg/dL as measured by CGM by up to about 26%”;
At claim 118, “avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 55 mg/dL as measured by CGM by up to about 24%”; and
At claim 119, “avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 40 mg/dL as measured by CGM by up to about 4%”.
However, the functionally defined durations fail to correspond to any structure/function relationships commensurate in scope with such limitations in the originally filed disclosure. Per MPEP § 2173.05(g),
[T]he 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. In re Swinehart, 439 F.2d 210, 213 (CCPA 1971). 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. . .
Here, the claims merely recite a description of functions or results to be achieved by the invention rather than a description of any specific structures or formulations required to achieve the desired outcomes, and therefore the claims are indefinite per MPEP § 2173.05(g). This is reasonable because MPEP § 2173 identifies that the primary purpose of the requirement is to inform the public of the boundaries of what constitutes infringement of the patent, but here it is unclear what specific number of days, dosage formulations, patient subpopulations, etc. are or are not sufficient to achieve the functional limitations. Accordingly, it is unclear what does or does not infringe upon the scope of instant claims 88, 117, 118, and 119 in view of the ambiguous functional language. Critically, close prior art exists and highly similar claim sets have either issued or are copending (see, e.g., Action mailed 11/05/2025 at 8-62; see also rejections below). Here, it is unclear if the “time sufficient to reduce the diurnal percent time” impacts the composition administered by altering specific excipients or carriers that must be present. This is pertinent in view of the close prior art of record, because the courts have stated that
Regardless 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).
Accordingly, because it is unclear what does or does not impact the functionally defined duration of treatment, and the functionally defined duration of treatment does not clearly and unambiguously refer on record to any specific length of hours, days, weeks, or administrations, an artisan would be unable to identify the metes and bounds of the claimed method, and therefore unable to distinguish between infringing and non-infringing claims. For purposes of applying prior art, the functionally defined durations at claims 88 and 117-119 are presumed fully satisfied by any prior art teaching or rendering obvious the treatment of humans diagnosed with PBH by subcutaneously administering 60 mg of Avexitide, once daily, for at least 14 days.
Claims 89-91, 94, 98-99, 102-103, 105, 107-108, 110, and 117-119 depend from (directed or indirectly) indefinite base claim 88, but fail to rectify the indefiniteness of the base claim. Accordingly, these claims are rejected for the reasons applicable to claim 88.
Accordingly, claims 88-91, 94, 98-99, 102-103, 105, 107-108, 110, and 117-119 are rejected.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 117 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 117 depends from claim 88. The claims recite functionally defined durations of treatment:
At claim 88, “for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 70 mg/dL as measured by CGM by about 4% to about 26%”;
At claim 117, “avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 70 mg/dL as measured by CGM by up to about 26%”;
At claim 88, the phrase “about” is undefined on record, but has been consistently understood to mean ±20% (see claim interpretation section above, and those of record), and therefore claim 88 is ostensibly limited to a range of time sufficient “to reduce diurnal percent time during which the subject’s glucose is less than 70 mg/dL as measured by CGM” by 3.2% to 31.2%. However, claim 117 more broadly encompasses a range of time sufficient “to reduce diurnal percent time during which the subject’s glucose is less than 70 mg/dL as measured by CGM” by “up to about 26%”, wherein “up to” is reasonably inferred to begin at 0%. Accordingly, claim 117 is understood to improperly be directed to a broader duration range than claim 88. Therefore, claim 117 is rejected as being of improper dependent form for failing to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a), New Matter
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 88-91, 94, 98-99, 102-103, 105, 107-108, 110, and 117-119 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.
Claim Scope
Claims 88 and 117-119 are representative of the pending claims scope and each recites a treatment method that lasts for a functionally defined amount of time, namely a “time sufficient” to achieve hoped and desired outcomes:
At claim 88, “for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 70 mg/dL as measured by CGM by about 4% to about 26%”;
At claim 117, “avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 70 mg/dL as measured by CGM by up to about 26%”;
At claim 118, “avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 55 mg/dL as measured by CGM by up to about 24%”; and
At claim 119, “avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 40 mg/dL as measured by CGM by up to about 4%”.
The relevant issue is that the phrase “for a time sufficient….”, and ranges of “about 4% to about 26%”, “up to about 26%”, “up to about 24%”, and “up to about 4%” do not appear in the originally filed disclosure and do not correspond to a structure/function relationship of record reasonably identifying how many daily administrations constitute “a time sufficient” to achieve the outcome now claimed.
Additional applicable claim interpretations have been set forth above under 35 USC § 112(b) and in a separate claim interpretation section. Those discussions are incorporated herein.
Lack of literal Support
The MPEP states that "[w]hile there is no in haec verba requirment, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP 2163.
No literal support exists for amended claim 88 or its dependents as filed 3/04/2026.
The functionally defined duration of treatment recited at claims 88 and 117-119, does not literally appear, as claimed, in the originally filed disclosure. Specifically, the following functionally defined “durations” do not literally appear on record:
At claim 88, “for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 70 mg/dL as measured by CGM by about 4% to about 26%”;
At claim 117, “avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 70 mg/dL as measured by CGM by up to about 26%”;
At claim 118, “avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 55 mg/dL as measured by CGM by up to about 24%”; and
At claim 119, “avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 40 mg/dL as measured by CGM by up to about 4%”.
In addition, the ranges of “about 4% to about 26%”, “up to about 26%”, “up to about 24%”, and “up to about 4%” are not literally disclosed in the originally filed application.
Accordingly, the pending claims lack literal support in the originally filed disclosure.
Lack of Implicit or Inherent Support
The MPEP states that "[w]hile there is no in haec verba requirment, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP 2163. As noted above, the claims are not literally supported by the originally filed disclosure. Accordingly, the relevant issue is whether or not the new amendments and resulting claim scope is implicitly or inherently supported by the originally filed disclosure.
Per MPEP § 2163(I)(B), “[a]n amendment to correct an obvious error does not constitute new matter where the ordinary artisan would not only recognize the existence of the error in the specification, but also recognize the appropriate correction. In re Oda, 443 F.2d 1200, 170 USPQ 268 (CCPA 1971)”. Here, no allegation that the amendments correct an obvious error has been made. Furthermore, upon inspection, Examiner is unable to identify any single “obvious error” that would lead to the instantly amended claim scope. Accordingly, the amendments cannot be said to correct an “obvious error”.
The closest support on record pertains to a set time period of at least 14 days (see, e.g., Spec. filed 4/14/2021 at ¶¶[0187], [0190], [0197], [0202], [0204], [0210]-[0211], [0214], [0242]-[0243] at Tables 8-9, [0278]), and time periods ranging from “at least 30 days” to “at least one year” or “the rest of the patient’s life” (see, e.g., Spec. filed 4/14/2021 at ¶¶[0067]). Accordingly, although the pending claim scope presumably encompasses a range of at least 14 days to less than 30 days (see instant claim 91), it is prima facie unknown what the minimum and maximum treatment durations required to satisfy the functional limitations of claims 88 and 117-119 may actually be.
Although Applicant directs the Examiner to paragraphs [0284] and [0316] of the published Application for support of the amendments filed 3/04/2026. These disclosures have been reviewed. However, paragraphs [0284] and [0316] of the published Application do not literally, inherently, or implicitly recite the ranges of “about 4% to about 26%”, “up to about 26%”, “up to about 24%”, and “up to about 4%”; furthermore paragraphs [0284] and [0316] of the published Application do not recite any functionally defined duration commensurate in scope with the instant claims. At best, [0284] of the published disclosure pertains to Figure 6, which is limited to 14-day periods of patients having <70 and <55 mg/dL glucose, wherein the data is highly variable as indicated by the large, overlapping error bars (see, e.g., instant Fig. 6). Notably, [0316] appears to not recite any relevant range or duration clearly relevant to the instant claims. Accordingly, these disclosures have been fully considered, but do not literally, inherently, or implicitly teach or disclose the ranges and functionally defined durations presently claimed, and fail to meaningfully correspond to a structure/function relationship permitting an artisan to identify a minimum time of treatment required to achieve the recited results.
Conclusion
Per MPEP § 2163, new or amended claims which introduce elements or limitations which are not supported by the as-filed disclosure violate the written description requirement (see, e.g., In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971)). Here, the newly added claim limitations are not inherently, implicitly, or literally supported by the originally filed disclosure.
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). Likewise, in the instant case, the claims are directed to methods of treating a functionally defined genus of diseases using unknown amounts of untested compounds, and have only identified generically “goals [Applicant] hope the claimed invention achieves”, and left it completely to others to actually invent and discover the specifics of the methods Applicant has attempted to claim.
Accordingly, claims 88-91, 94, 98-99, 102-103, 105, 107-108, 110, and 117-119 are rejected as directed to new matter.
To facilitate compact prosecution, for purposes of applying prior art, the functionally defined durations at claims 88 and 117-119 are presumed fully satisfied by any prior art teaching or rendering obvious the treatment of any humans diagnosed with PBH by a treatment comprising subcutaneously administering 60 mg of Avexitide, once daily, for at least 14 days.
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.
[Prior Art Rejection 01]
Claims 88-91, 94, 98-99, 102-103, 105, 107-108, 110, and 117-119 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/191394 A1 (Dec. 1, 2016; cited in IDS filed 10/11/2024 as cite No. 73).
Claim interpretation: The applicable claim interpretation has been set forth in preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. An artisan would readily understand that avexitide is exendin(9-39)2. Regarding the functionally defined duration of treatment as set forth at amended claims 88 and 117-119, this language has been rejected and addressed above under 35 USC §112(a) and §112(b). To facilitate compact prosecution, the functionally defined durations at claims 88 and 117-119 are presumed fully satisfied the treatment of any humans diagnosed with PBH by a treatment comprising subcutaneously administering 60 mg of Avexitide, once daily, for at least 14 days. Additional claim interpretations are set forth below.
Regarding instant claims 88, 117-119, and the treatment of subjects diagnosed with post-bariatric hypoglycemia (PBH) by subcutaneously administering to the subject avexitide, WO’394 claims methods of treating and preventing hypoglycemia in patients that have previously had bariatric surgery (see, e.g., WO’394 at claims 1-4), by subcutaneous administration of exendin(9-39) (see, e.g., WO’394 at claims 1-3 and 5), wherein the exendin(9-39) may be administered “once daily” (see, e.g., WO’394 at ¶¶[0076]-[0077], [0107]), wherein the therapeutically effective doses range from 2-100 mg of exendin(9-39) (see, e.g., WO’394 at ¶[0006]), and “adult patients (60-100 kg or more) will receive therapeutic benefit from a single dose in the range of 10-75 mg” (see, e.g., WO’394 at ¶[0006]). Regarding instant claims 88, 91, 117-119, and treatment durations of “30 days or less”, amended claims 88 and 117-119 recite functionally defined treatment durations, which have been rejected under 35 USC §§112(a) and (b), above. For purposes of the instant rejection, the duration recited at claim 91 is understood to satisfy such limitations, namely “30 days or less” (see, e.g., instant claim 91). This is pertinent because WO’394 discloses that the “duration of therapy” may be “continued on a continuous daily” basis for “at least 30 days” up to “at least one year”, or even up to “the rest of the patient’s life” (see, e.g., WO’394 at ¶[0120]), which overlaps in scope with “30 days or less”. Regarding instant claims 89-90, 98, and avexitide administered as a buffered liquid formulation comprising avexitide at a concentration from 30 mg/ml to 180 mg/ml, in a volume of 0.25 ml to 1.5 ml, WO’364 identifies that the pharmaceutical composition administered may be a buffered liquid formulation suitable for subcutaneous administration (see, e.g., WO’394 at ¶¶[0096]-[0097], claims 1-4); and discloses that such formulations may have a concentration of 20-45 mg/mL (see, e.g., WO’394 at ¶[0085]), wherein the volume may vary from 0.25-2 mL volume (see, e.g., WO’394 at ¶[0095]). Regarding instant claim 94, and post-bariatric hypoglycemia patients that have previously had one of any enumerated gastric surgeries, WO’394 is understood to direct artisans to treat hypoglycemia in patients that have previously had bariatric surgery (see, e.g., WO’394 at claims 1-2 and 4), including in patients having a vertical sleeve gastrectomy (VSG) and other gastrointestinal surgeries (compare instant claim 94 with WO’394 at claims 1-2 and 4, ¶[0055]). Regarding instant claim 99 and treatment of a subject refractory to dietary treatment for PBH, WO’395 teaches a methodology of treating all HH patients following bariatric surgery, which would necessarily include any and all such patients satisfying such diagnosis, without distinction to those that also happen to be refractory to other treatments (see, e.g., WO’394 at claims 1-5). Accordingly, in view of primary reference, an artisan would treat such subpopulations of patients the same way, whether refractory to dietary treatment or not, with the same expected and predicted outcome, namely successful treatment of HH after bariatric surgery. Therefore, instant claim 99 does not patentably distinguish the claimed invention in view of the issued claims. Regarding instant claims 102, 103, and once daily administration in the morning, 45-90 minutes prior to a morning meal, WO’394 explicitly discusses the timing of once daily administrations relative to meals (see, e.g., WO’394 at ¶¶[0074], [0077]-[0079], [0082]), wherein WO’394 identifies that a once daily administration (qD or QD) may be administered “with each meal”, wherein “it being understood that ‘with each meal’ typically refers to a set period (at least 60 minutes, for example) before a meal, e.g., the first or last meal of the day” (see, e.g., WO’394 at ¶[0074]), wherein once daily administration may be in the morning (see, e.g., WO’394 at ¶[0077]), and wherein administration is within 60-150 minutes prior to a morning meal (see, e.g., WO’394 at ¶[0078]). Regarding instant claim 102 and the requirement to “fast overnight”, it is readily apparent that patients would not reasonably be expected to eat while sleeping, and therefore would be reasonably presumed to necessarily “fast overnight” while sleeping. Regarding instantly amended claims 105, 107-108, and 110 and the recitation of intended or expected results that “the method results in” within a subject following treatment as recited by instant claim 88, instantly amended claims 105, 107-108, and 110 are understood to recite a “wherein” clause expressing the intended and expected results that would necessarily and inherently occur upon the successful completion of the positively recited method steps of amended claim 88, because these claims do not recite nor require additional steps to be performed (see, e.g., MPEP § 2111.04(I)). This is reasonable because none of the limitations at claims 105, 107, 108, or 110 correspond to a functional limitation or structure/function teaching commensurate in scope with the instant claims. Accordingly, the intended and expected results of instant claims 105, 107, 108, and 110 are understood to be fully satisfied by any prior art methodology teaching or otherwise rendering obvious a method wherein any human diagnosed with PBH is subcutaneously administered 60 mg of Avexitide, once daily, for “30 or less days” (see instant claim 91). Accordingly, these claims are rejected for the reasons applied to instant claim 88, set forth in the instant rejection. Regarding claims 88, 117-119, and recitations of specific glucose levels and continuous glucose monitoring, WO’395 informs artisans that
…hypoglycemia is defined as a plasma glucose concentration of ≤ 55 mg/dL by continuous glucose monitoring…
(see, e.g., WO’394 at ¶[0177]).
Accordingly, WO’395 informs artisans that hypoglycemia, and therefore the patient population treated by the pending claims, includes all patients having hypoglycemia as defined as a glucose concentration of ≤ 55 mg/dL by continuous glucose monitoring (see, e.g., WO’394 at ¶[0177]), wherein the range of ≤ 55 mg/dL (i.e., 0 to 55 mg/dL) overlaps in scope with the instantly claimed ranges. Therefore, treatment of hypoglycemia in patients having a glucose concentration of 0 to 55 mg/dL as measured by CGM would be obvious in view of the teachings of WO’394. Predicted and expected results of performing the prior art methodology as described by WO’394: WO’394 reasonably informs artisans that the treatment disclosed would desirably result in the predicted and expected treatment of HH in post-bariatric patients (see, e.g., WO’394 at claims 1-5). , wherein morning administration would be predicted and expected “to provide protection during the day (e.g., lunch, dinner, or multiple small meals during the day” (see, e.g., WO’394 at ¶[0081]), wherein “during the day” would be understood to refer to diurnal hours.
WO’395 differs from the instant claims as follows: Although WO’394 teaches and discloses methods of treating the same patient population (i.e., HH patients following bariatric surgery) by administering the same compound (i.e., exendin(9-39)) via the same administration route (i.e., subcutaneous), at the same or overlapping dosage (i.e., once daily at “10-75 mg”), at the same or overlapping daily time (i.e., once daily 60-150 minutes before a morning meal), for the same or overlapping treatment duration (i.e., 30 days or more), to achieve a known result (i.e., treatment of hypoglycemia), WO’394 does not explicitly reduce the exact method as claimed to practice.
Accordingly, the issue is whether or not it would be obvious to treat a known patient population with a known compound via a known administration route within a known dosage range, and within a known dosage frequency, and within a known treatment duration range, wherein such treatment merely produces a known, predicted and expected outcome. Accordingly, the instant claims merely represent a variation of the prior art teachings, wherein all claimed parameters occur within known ranges taught by the prior art (see also MPEP § 2144.05(I), noting 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), and yield the expected and predicted outcome taught by the prior art. The Court has stated that
"[W]hen a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious."
KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 , 417 , 127 S. Ct. 1727 , 167 L. Ed. 2d 705 (2007) (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273 , 282 , 96 S. Ct. 1532 , 47 L. Ed. 2d 784 (1976)).
Likewise, the Supreme Court has rejected rigid tests for obviousness and has emphasized that
[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.”
KSR Int'l v. Teleflex Inc., 550 U.S. 398, 415 (2007), at 416.
And has also emphasized that
“If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.”
KSR Int'l v. Teleflex Inc., 550 U.S. 398, 415 (2007), at 417.
Here, all aspects of the claimed method were already known in the art, and all parameters claimed appear to be taught explicitly or otherwise overlap in scope with the ranges explicitly taught and disclosed by the prior art.
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(s): It would have been obvious to arrive at the claimed invention because the invention is the combination of known elements according to known methods, and namely pertains to a prior art method of treating HH in a known patient population (i.e., patients having HH post-bariatric surgery), by administering a known compound (i.e., exendin(9-39)), via a known administration route (i.e., subcutaneous) within a known dosage range (e.g., 10-75 mg), at the same or overlapping daily time (i.e., once daily 60-150 minutes before a morning meal), within a known treatment duration (e.g., 30 days or more), wherein such treatment merely produces a known, predicted and expected outcome (i.e., treatment of hypoglycemia), and each element merely performs its art-recognized function in combination as it does separately (see, e.g., MPEP § 2143(I)(A), (C), (D), (G); MPEP § 2144.05(I)).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 (e.g., criticality of range) have been placed on record to date.
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 to treat a known disease or condition in a known patient population using a known therapeutic compound administered via a known route at a known frequency and known concentration, to achieve the exact result taught and disclosed by the prior art, namely treatment of HH.
Claims 88-91, 94, 98-99, 102-103, 105, 107-108, 110, and 117-119 are rejected.
[Prior Art Rejection 02]
Claims 88-91, 94, 98-99, 102-103, 105, 107-108, 110, and 117-119 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/191395 A1 (Dec. 1, 2016; cited in previous action) in view of WO2017/152014 A1 (Sept. 8, 2017; cited in previous action).
Claim interpretation: The applicable claim interpretation has been set forth in preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. An artisan would readily understand that avexitide is exendin(9-39)3. Regarding the functionally defined duration of treatment as set forth at amended claims 88 and 117-119, this language has been rejected and addressed above under 35 USC §112(a) and §112(b). To facilitate compact prosecution, the functionally defined durations at claims 88 and 117-119 are presumed fully satisfied the treatment of any humans diagnosed with PBH by a treatment comprising subcutaneously administering 60 mg of Avexitide, once daily, for at least 14 days. Additional claim interpretations are set forth below.
Regarding instant claims 88, 91, and 117-119 and the subcutaneous administration of avexitide to human subjects with Post-bariatric hypoglycemia (PBH) at 60 mg per day for at least 14 days, WO’395 pertains to the treatment of human subjects with hyperinsulinemic hypoglycemia after bariatric surgery by subcutaneously administering exendin(9-39) daily (see, e.g., WO’395 at title, abs), wherein exendin(9-39) may be administered twice-per-day at 30 mg, which is 60 mg total per day (see, e.g., WO’395 at ¶¶[0006]-[0007]); wherein WO’395 identifies that patients may be treated for “at least 30 days”, which is “at least 14 days” but also “for 30 days or less” (see, e.g., WO’395 at ¶[0104]; see also WO’395 at ¶¶[0152], [0155], [0156], [0157]). Regarding instant claim 89-90, 98, and the volume and concentration of avexitide administered, WO’395 explicitly teaches the volume range of 0.7 to 1 mL (see, e.g., WO’395 at ¶¶[0084]; see also id. at claim 9), and explicitly exemplifies the volume of 0.7 ml (see, e.g., WO’395 at ¶¶[0129]-[0130], [0134]. Table 4 on 45, Table 5 on 46). In addition, WO’395 exemplifies the usage of the concentration ranges of 10-25 mg/mL (see, e.g., WO’395 at Table A at ¶[0081]) and informs artisans that exendin(9-39) may be subcutaneously administered at a concentration of “about 25 mg/mL” (see, e.g., WO’395 at ¶[0077]), wherein “about” would be understood to reasonably include 30 mg/mL (i.e., at least ±20%). Regarding instant claim 94, and a human patient population having post-bariatric hypoglycemia (PBH) in patients that previously had a gastric bypass surgery, WO’395 identifies that the disclosed methods are applicable to patients with PBH (see, e.g., WO’395 at title, abs) including patients having hyperinsulinemic hypoglycemia (HH) after gastric bypass surgery (see, e.g., WO’395 at ¶¶[0035], [0051], [0053]-[0054], claims 1, 9, 13-15, 31). Regarding instant claim 99 and cases wherein a patient is refractory to dietary treatment, WO’395 teaches a methodology of treating all HH patients following bariatric surgery, which would necessarily include any and all such patients satisfying such diagnosis, without distinction to those that also happen to be refractory to other treatments (see id. at claims 1, 9, 14-15, 31; see also id. at ¶¶[0035], [0051], [0053]-[0054]). Accordingly, in view of primary reference, an artisan would treat such patients the same way, whether refractory to dietary treatment or not, with the expected and predicted outcome of successfully treating HH after bariatric surgery. Therefore, instant claim 99 does not patentably distinguish the claimed invention in view of the issued claims. Regarding claims 102, 103, and morning administration of avexitide, WO’395 explicitly directs artisans to treat HH by subcutaneously administrating, BID, 30 mg of exendin(9-39) in an injection volume of 0.5 to 1 mL (see, e.g., WO’395 at claims 1, 9, 13-15), wherein the “morning administration” is administered 60-90 minutes before the morning meal (see, e.g., WO’395 at claims 1, 9, 13-15). Accordingly, an artisan would appreciate that “morning administration” would occur after sleeping (i.e., fasting overnight), and taking avexitide 60-90 minutes before a morning meal would necessarily require fasting between 60-90 minutes prior to a morning meal, which overlaps with the instantly claimed ranges (see also MPEP § 2144.05(I), noting 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 instantly amended claims 105, 107-108, and 110 and the recitation of intended or expected results that “the method results in” within a subject following treatment as recited by instant claim 88, instantly amended claims 105, 107-108, and 110 are understood to recite a “wherein” clause expressing the intended and expected results that would necessarily and inherently occur upon the successful completion of the positively recited method steps of amended claim 88, because these claims do not recite nor require additional steps to be performed (see, e.g., MPEP § 2111.04(I)). This is reasonable because none of the limitations at claims 105, 107, 108, or 110 correspond to a functional limitation or structure/function teaching commensurate in scope with the instant claims. Accordingly, the intended and expected results of instant claims 105, 107, 108, and 110 are understood to be fully satisfied by any prior art methodology teaching or otherwise rendering obvious a method wherein any human diagnosed with PBH is subcutaneously administered 60 mg of Avexitide, once daily, for at least 14 days. Accordingly, these claims are rejected for the reasons applied to instant claim 88, set forth in the instant rejection. Regarding claims 88, 117-119, and recitations of specific glucose levels and continuous glucose monitoring, WO’395 informs artisans that
…hypoglycemia is defined as a plasma glucose concentration of ≤ 55 mg/dL by continuous glucose monitoring…
(see, e.g., WO’395 at ¶[0157]).
Therefore, the recitations at instant claims 88 and 117-119 pertaining to plasma glucose concentrations determined by continuous glucose monitoring are understood to fall within the prior art ranges and definitions for hypoglycemia (see, e.g., WO’395 at ¶[0157]), and it would therefore be obvious to treat such patients using CGM using the methods of WO’395 (see, e.g., WO’395 at abs, Fig. 4A-C; see also id. at ¶¶[0059], [0157]; see also MPEP § 2144.05(I), noting 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 the elected species of an avexitide injection consisting of 30 mg/mL exendin(9-39) in a sodium acetate buffer containing mannitol as a tonicity modifier, in 1 mL of solution, WO’395 directs artisans to formulate exendin(9-39) with the tonicity-adjusting agent of mannitol and a buffer to bring the solution to a pH of about 4-5 (see, e.g., WO’395 at ¶¶[0086], [0094], [0096]). Furthermore, WO’395 identifies that the acetate salt of exendin(9-39) is utilized (see, e.g., WO’395 at ¶¶[0044], [0118], [0130]), and is utilized in normal saline (see, e.g., WO’395 at ¶¶[0086], [0094], [0096], [0118], [0129]-[0130], [0141]), which would be reasonably understood to form a sodium acetate buffer in solution. In sum, WO’395 is understood to teach and direct artisans to treat the same patient population by administering the same compound via the same administration route at the same daily dosage, wherein the treatment duration appears to materially overlap in scope.
WO’395 differs from the instant claims as follows: Although WO’395 teaches methods of administering the same compound (i.e., avexitide or exendin(9-39)) via the same administration route (subcutaneous) at the same total daily concentration (i.e., 60 mg per day), for the same length of time (i.e., 30 days), in order to obtain the same results (i.e., the treatment of HH in diagnosed HH patients following bariatric surgery), WO’395 directs artisans to twice daily administration (i.e., 30 mg twice daily (60 mg total)), whereas the instantly amended claims are directed to 60 mg once daily (QD).
However, WO’395 does identify and disclose that “adult patients…will receive therapeutic benefit from a single dose of exendin(9-39)” (see, e.g., WO’395 at ¶[0104]). Accordingly, an artisan would readily review the prior art for guidance regarding single dose exendin(9-39) or related guidance pertaining to exendin derivatives, generally. To this end, an artisan would reasonably review WO’014, which, like the primary reference, pertains to the treatment of HH in patients following bariatric surgery by administering exendin-4 derivatives, which include exendin(9-39) (see, e.g., WO’014 at ¶¶[0002], [0015], [0035], [0066], [0068]. [0070]). Although WO’014 focuses primarily upon exendin-4 derivatives other than exendin(9-39), an artisan would readily appreciate that the disclosure was applicable to the treatment of HH using exendin-4 derivatives, generally. Regarding dosages, concentrations, and instant claims 88-90, and 98, WO’014 discloses that it was generally known in the prior art that exendin-4 derivatives may be subcutaneously administered to treat HH at amounts of 10-75 mg QD (once daily) (see, e.g., WO’014 at ¶¶[0046], [0049]), wherein it may have a concentration on “about 4-50 mg/mL” (see, e.g., WO’014 at ¶[0050]), and wherein the volume is 0.5 to 1.5 mL or 0.7 to 1 mL (see, e.g., WO’014 at ¶[0050]) (see also MPEP § 2144.05(I), noting 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(s): It would have been obvious to arrive at the claimed invention because the invention is the treatment of a prior art-recognized patient population (i.e., patients having HH post-bariatric surgery) by administering a prior art compound (i.e., the exendin derivative of exendin(9-39)) via the same administration route (i.e., subcutaneous), at the same total daily dosage (i.e., a total of 60 mg), for the same length of time (i.e., at least 30 days), exactly as taught by the primary reference, but wherein the total amount of 60 mg is merely administered in a single daily dosage rather than twice-daily dosages as suggested by the secondary reference; such difference would predictably and expectedly yield the exact results taught and suggested by the primary and secondary references, namely the successful treatment of patients in need of treatment for HH post-bariatric surgery (see, e.g., MPEP § 2143(I)(A), (B), (C), (D), (G); MPEP § 2144.05(I)). Furthermore, each element merely performs its art-recognized function in combination as it does separately.
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 to treat a known disease or condition in a known patient population using a known therapeutic compound administered via a known route at a known frequency and concentration, to achieve the exact result taught and disclosed by the prior art, namely treatment of HH.
Claims 88-91, 94, 98-99, 102-103, 105, 107-108, 110, and 117-119 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.
[NSDP Rejection 01]
Claims 88-91, 94, 98-99, 102-103, 105, 107-108, 110, and 117-119 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 10639354 B2. Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Regarding the functionally defined duration of treatment as set forth at amended claims 88 and 117-119, this language has been rejected and addressed above under 35 USC §112(a) and §112(b). To facilitate compact prosecution, the functionally defined durations at claims 88 and 117-119 are presumed fully satisfied the treatment of any humans diagnosed with PBH by a treatment comprising subcutaneously administering 60 mg of Avexitide, once daily, for at least 14 days. Additional claim interpretations are set forth below.
Applicable legal analysis: The applicable analysis for Nonstatutory Double Patenting is set forth at MPEP § 804(II), and specifically at MPEP § 804(II)(B). Here, although the same invention is not being claimed twice (see, e.g., MPEP § 804(II)(A), discussing Statutory Double Patenting), a Nonstatutory Double Patenting rejection is appropriate because although the conflicting claims are not identical, at least one examined application claim is not patentably distinct from the reference claims because the examined application claim is either anticipated by, or would have been obvious over, the reference claims for the reasons set forth in the following paragraph4: Per MPEP § 804(II)(B), “To decide the question above, the examiner should first construe the claim(s) in the application under examination and the claim(s) in the reference application or patent to determine what are the differences”. Accordingly, a comparison of the teachings of the reference claims and the instant pending claims are set forth below:
Summary of the pending claim scope: The instant claims are understood to be directed to a method of treating any patient having post-bariatric hypoglycemia (PBH) (post gastric bypass surgery) by subcutaneously administering Avexitide (i.e., exendin(9-39)) once daily at least at 60 mg for a functionally defined amount of time (presumably at least 14 days) (see, e.g., instant claims 88 and 117-119). Amended claims 88 and 117-119 recite a functionally defined treatment duration, wherein the duration length is functionally limited by the recitation of desired outcomes Applicant hopes and wishes for the invention to achieve (see, e.g., instant claim 88, 117-119), which have necessitated rejections under 35 USC §112(a) and §112(b), above. For purposes of the instant rejection, claims 88 and 117-119 are presumed fully satisfied by treatment of any humans diagnosed with PBH by subcutaneously administering 60 mg of Avexitide, once daily, for at least 14 days. Instant claims 105, 107-108, 110, and 117-119 are understood to recite and refer to a “wherein” clause expressing the intended and expected results of the positively recited method steps of claim 88 (i.e., the subcutaneous administration of Avexitide into a patient in need thereof), and therefore such claims are understood to be rendered obvious for reasons applicable to instant claim 88 (see, e.g., MPEP § 2111.04(I); see also originally elected subgenus of patentably indistinct variants).
Regarding instant claim 88, 94, and the treatment of post-bariatric hypoglycemia following gastric bypass, the primary reference claims the treatment of HH following bariatric surgery, including gastric bypass surgery (see, e.g., US’354 at claims 1, 6-7). Regarding instant claim 88 and the subcutaneous administration of “at least 60 mg of avexitide” in a single day, US’354 claims the treatment of the same or overlapping patient population by subcutaneously administering exendin(9-39) (i.e., avexitide) at 30 mg twice daily, for a daily total of 60 mg (see, e.g., US’354 at claims 1-2, 6-7, 12-13, 23). Regarding instant claims 88, 91, 117-119, and the duration of treatment from a functionally defined minimum amount of days (e.g., “a time sufficient to reduce the diurnal percent time…” to “for 30 days or less”, US’354 claims methods of administration for “at least 30 days”, wherein “30 days” is “at least 14 days” but also “30 days or less” (compare instant claims 88, 91, and 117-119 with US’354 at claims 1 and 23). Regarding amended claims 88, 117-119, and the treatment of hypoglycemic patients “having glucose values of <70 mg/dL” as measured by CGM, the primary reference is understood to be applicable to patients “in need thereof” of treatment for HH, including in post-bariatric surgery (see, e.g., US’354 at claims 1, 6-7), but it does not specifically recite the ranges of “glucose values” as recited at amended claims 88 and 117-119. However, 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)). This is pertinent because “hypoglycemia” is understood as follows:
..where hypoglycemia is defined as a plasma glucose concentration of ≤55 mg/dL by continuous glucose monitoring…
(see, e.g., US’354 at col. 30 at lines 55-65).
Accordingly, “hypoglycemia” necessarily refers to and requires plasma glucose concentrations values at or below under 55 mg/mL (see, e.g., id.). Accordingly, a hypoglycemic patient “in need” of the methods set forth in the issued claims would be readily understood to overlap in scope with the instant recitations at claims 88 and 117-119 (see also MPEP § 2144.05(I), noting 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 89-90, 98, and the volume and concentration limitations, US’354 recites 30 mg BID treatment with an injectate volume of 0.5 ml, which would yield 60 mg/mL concentration (see, e.g., US’354 at claims 1-2). Regarding instant claim 99 and refractory subjects, US’354 claims a treatment of all HH patients following bariatric surgery, including gastric bypass surgery (see, e.g., US’354 at claims 1, 6-7), which would necessarily encompass any patients at all satisfying such medical requirements, including those that are refractory to other treatments (see id). Accordingly, in view of primary reference, an artisan would treat such patients the same way, whether refractory or not. Therefore, instant claim 99 does not patentably distinguish the claimed invention in view of the issued claims. Regarding instant claims 102-103 and having a meal within 90 minutes of a dose, the primary reference explicitly claims having a morning meal within 60-90 minutes of a dosage (see, e.g., US’354 at claim 4), which would necessarily require fasting overnight, and 60-90 minutes of fasting prior to a morning dosage. Regarding instant claims 105, 107-108, 110, and the intended or expected results of performing the method at instant claim 88, instantly amended claims 105, 107, 108, and 110 are understood to recite a “wherein” clause expressing the intended and expected results that would necessarily and inherently occur upon the successful completion of the positively recited method steps of amended claim 88, because these claims do not recite nor require additional steps to be performed (see, e.g., MPEP § 2111.04(I)). Accordingly, the intended or expected results of claims 105, 107, 108, and 110 are understood to be fully satisfied by any prior art methodology that requires the active method steps of instant claim 88. Accordingly, claims 105, 107-108, and 110 are rejected for the reasons applied to instant claim 88, above.
The difference: The difference between the issued claims and the instant claims appears to be minor since both claim sets pertain to methods of treating the same or overlapping patient populations by administering the same compound (i.e., avexitide or exendin(9-39)) via the same administration route (subcutaneous) at the same total daily concentration (i.e., 60 mg per day), for the same length of time (i.e., 30 days), in order to obtain the same basic results, namely the treatment of HH in HH patients following bariatric surgery. The sole difference appears to be that the issued claims are directed to BID administration of 30 mg twice daily (60 mg total), whereas the instantly amended claims are directed to 60 mg once daily (QD).
The answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”5 is “yes”. MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). Here, the time between BID dosages is not limited in the issued claims and may be seconds or minutes apart, wherein the QD administration may be administered over 5 or more minutes, and therefore there may be no real difference between the inventions as presently claimed. In addition, in response to the election of species requirement, Applicant made no distinction between 30 mg BID and 60 mg QD, and therefore such species are understood to be obvious variants on record. In addition, or alternatively, per MPEP § 2144.05(II),
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Here, optimization of concentration and dosing frequency is routine in the prior art, and no criticality of range has been shown on record, and therefore an artisan would readily appreciate that the administration of 60 mg BID or QD would lead to a daily administered amount of 60 mg, which would be expected and predicted to treat HH in PBH patients (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2144.05(II)). Therefore, the instant claims are directed to obvious variants of the issued claims.
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.
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 88-91, 94, 98-99, 102-103, 105, 107-108, 110, and 117-119 are rejected.
[NSDP Rejection 02]
Claims 88-91, 94, 98-99, 102-103, 105, 107-108, 110, and 117-119 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10660937 B2. Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Applicable legal analysis: The applicable legal analysis for non-statutory double patenting rejections have been set forth above in a preceding rejection, and that discussion is incorporated herein, but not repeated.
Summary of the pending claim scope: The summary of the pending claim scope has been set forth above in a preceding non-statutory double patenting rejection, and that discussion is incorporated herein, but not repeated.
Regarding instant claim 88, 94, and the treatment of post-bariatric hypoglycemia following gastric bypass, the primary reference claims the treatment of HH following bariatric surgery, including gastric bypass surgery (see, e.g., US’937 at claims 1, 3-5). Regarding instant claim 88 and the subcutaneous administration of “at least 60 mg of avexitide” in a single day and in a single injection “once daily”, the reference claims the treatment of the same or overlapping patient population by subcutaneously administering exendin(9-39) (i.e., avexitide) at 2-100 mg by subcutaneous administration “once per day”, including 75 mg per dose (see, e.g., US’937 at claims 1-2, 13-16, and 17; wherein claim 17 encompasses administration using a syringe or pen injector). Regarding instant claims 88, 91, 117-119, and the duration of treatment from a functionally defined minimum number of days (e.g., “a time sufficient to reduce the diurnal percent time…” to “for 30 days or less”, the primary reference claims methods of administration without a specific duration, but for the purpose of treating a patient with HH after bariatric surgery (see, e.g., US’937 at claims 1 and 3-4). However, per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’937 at col. 24 to 25 at bridging ¶), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id). Accordingly, such durations are obvious variants of the claimed method since such duration amounts to the repetition of known steps for 30 days or more as taught for such therapies. Regarding amended claims 88, 117-119, and the treatment of hypoglycemic patients “having glucose values of <70 mg/dL” as measured by CGM, the primary reference is understood to be applicable to patients “in need thereof” of treatment for HH, including in post-bariatric surgery (see, e.g., US’937 at claims 1, 3-4), but it does not specifically recite the ranges of “glucose values” as recited at amended claims 88 and 117-119. However, 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)). This is pertinent because “hypoglycemia” is understood as follows:
..where hypoglycemia is defined as a plasma glucose concentration of ≤55 mg/dL by continuous glucose monitoring…
(see, e.g., US’937 at col. 38 at lines 35-45).
Accordingly, “hypoglycemia” necessarily refers to and requires plasma glucose concentrations values at or below under 55 mg/mL (see, e.g., id.). Accordingly, a hypoglycemic patient “in need” of the methods set forth in the issued claims would be readily understood to overlap in scope with the instant recitations at claims 88 and 117-119 (see also MPEP § 2144.05(I), noting 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 89-90, 98, and the volume and concentration limitations, the primary reference recites “once per day” injections of 2-100 mg with a concentration of 45 mg/mL (see, e.g., US’937 at claims 1-2). Accordingly, this concentration range and dosage range encompasses 60 mg delivered at least at 1.334 mL. Regarding instant claim 99 and refractory subjects, the primary reference claims a treatment of all HH patients following bariatric surgery, including gastric bypass surgery (see, e.g., Ref at claims 1-5), which would necessarily encompass any patients at all satisfying such medical requirements, including those that are refractory to other treatments (see id). Accordingly, in view of primary reference, an artisan would treat such patients the same way, whether refractory or not. Therefore, instant claim 99 does not patentably distinguish the claimed invention in view of the issued claims. Regarding instant claims 102-103 and having a meal within 90 minutes of a dose, the primary reference explicitly claims having a morning meal within 60-90 minutes of a dosage (see, e.g., Reference at claim 12), and therefore an artisan would readily appreciate that such dosages could be administered after fasting overnight, and 60-90 minutes prior to a meal (see also MPEP § 2144.05(I), noting 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 105, 107-108, 110, and the intended or expected results of performing the method at instant claim 88, instantly amended claims 105, 107, 108, and 110 are understood to recite a “wherein” clause expressing the intended and expected results that would necessarily and inherently occur upon the successful completion of the positively recited method steps of amended claim 88, because these claims do not recite nor require additional steps to be performed (see, e.g., MPEP § 2111.04(I)). Accordingly, the intended or expected results of claims 105, 107, 108, and 110 are understood to be fully satisfied by any prior art methodology that requires the active method steps of instant claim 88. Accordingly, claims 105, 107-108, and 110 are rejected for the reasons applied to instant claim 88, above.
The difference: The difference between the issued claims and the instant claims appears to be minor since both claim sets pertain to methods of treating the same or overlapping patient populations by administering the same compound (i.e., avexitide or exendin(9-39)) via the same administration route (subcutaneous) at the same “once daily” concentration (i.e., >60 mg per day), in order to obtain the same basic results, namely the treatment of HH in HH patients following bariatric surgery. The sole difference appears to be that the issued claims are directed to a method of treating patients for an unspecified length of time rather than “at least 14 days” and “30 days or less”.
The answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”6 is “yes”. MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). Here, regarding the difference in duration of treatment, the reference claims a method of treating a patient in need of treatment for HH, and therefore such treatment would be continued for as long as needed7. Therefore, regarding the duration of treatment, the simple repetition of a known step to achieve an art-recognized outcome is “merely the logical result of common sense application of the maxim ‘try, try again’” (see, e.g., Perfect Web Technologies, Inc. v. InfoUSA, Inc. 587 F.3d 1324 (Fed. Cir. Dec. 2, 2009)). In the instant case, an artisan would understand that repeating the reference claim method would predictably lead to the successful treatment of HH in a patient in need thereof, and therefore an artisan would readily appreciate that such steps could be repeated to logically achieve the exact outcome identified in the issued claims, namely treatment of a patient in need of HH treatment. Accordingly, the length of treatment duration could be for any desired time period, such as a clinical trial (i.e., weeks), hospital stay (days or weeks), or potentially over a lifetime. Accordingly, claims directed to the length of treatment do not materially or substantially differentiate the claimed invention relative to the teachings of the prior art. Accordingly, the present claims are directed to obvious variants of the reference claims because it is well-within the ordinary skill in the art to practice claimed methods of treating known conditions in known patient populations by administering known compounds within known therapeutically effective ranges to achieve a known outcome, and to simply repeat such treatment for the duration needed (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (C), (D), and (G), 2144.05(I)). Therefore, the instant claims are directed to obvious variants of the issued claims.
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 variant of the patented 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 88-91, 94, 98-99, 102-103, 105, 107-108, 110, and 117-119 are rejected.
[NSDP Rejection 03]
Claims 88-91, 94, 98-99, 105, 107-108, 110, and 117-119 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 10993992 B2. Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Applicable legal analysis: The applicable legal analysis for non-statutory double patenting rejections have been set forth above in a preceding rejection, and that discussion is incorporated herein, but not repeated.
Summary of the pending claim scope: The summary of the pending claim scope has been set forth above in a preceding non-statutory double patenting rejection, and that discussion is incorporated herein, but not repeated.
Regarding instant claim 88, 94, and the treatment of post-bariatric hypoglycemia following gastric bypass, the primary reference claims the treatment of HH following bariatric surgery, including gastric bypass surgery (see, e.g., US’992 at claims 1, 7-9, 17-20). Regarding instant claims 88, 117-119, and the subcutaneous administration of “at least 60 mg of avexitide” in a single day and in a single injection “once daily”, the reference claims the treatment of the same or overlapping patient population by subcutaneously administering exendin(9-39) (i.e., avexitide) at 2-100 mg by subcutaneous administration “once per day”(see, e.g., US’992 at claims 1-2, 15, 17-20, 31). Regarding instant claims 88, 91, 117-119, and the duration of treatment from a functionally defined minimum number of days (e.g., “a time sufficient to reduce the diurnal percent time…” to “for 30 days or less”, the primary reference claims methods of administration without a specific duration, but for the purpose of treating a patient with HH after bariatric surgery (see, e.g., US’992 at claims 1 and 6-7, 15). However, per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’992 at col. 24 at lines 37-50), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id). Accordingly, such durations are obvious variants of the claimed method since such duration amounts to the repetition of known steps for 30 days or more as taught for such therapies. Regarding amended claims 88, 117-119, and the treatment of hypoglycemic patients “having glucose values of <70 mg/dL” as measured by CGM, the primary reference is understood to be applicable to patients “in need thereof” of treatment for HH, including in post-bariatric surgery (see, e.g., US’992 at claims 1, 7-10, 18-20), but it does not specifically recite the ranges of “glucose values” as recited at amended claims 88 and 117-119. However, 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)). This is pertinent because “hypoglycemia” is understood as follows:
..where hypoglycemia is defined as a plasma glucose concentration of ≤55 mg/dL by continuous glucose monitoring…
(see, e.g., US’992 at col. 37 at lines 60-67).
Accordingly, “hypoglycemia” necessarily refers to and requires plasma glucose concentrations values at or below under 55 mg/mL (see, e.g., id.). Accordingly, a hypoglycemic patient “in need” of the methods set forth in the issued claims would be readily understood to overlap in scope with the instant recitations at claims 88 and 117-119 (see also MPEP § 2144.05(I), noting 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 89-90, 98, and the volume and concentration limitations, the primary reference recites “once per day” injections of 2-100 mg with a concentration of 45 mg/mL (see, e.g., US’992 at claims 1-2, 15, 17-20, 31). Accordingly, this concentration range and dosage range encompasses 60 mg delivered at least at 1.334 mL. Regarding instant claim 99 and refractory subjects, the primary reference claims a treatment of all HH patients following bariatric surgery, including gastric bypass surgery (see, e.g., Ref at claims 1-2, 15, 17-20, 31), which would necessarily encompass any patients at all satisfying such medical requirements, including those that are refractory to other treatments (see id). Accordingly, in view of primary reference, an artisan would treat such patients the same way, whether refractory or not. Therefore, instant claim 99 does not patentably distinguish the claimed invention in view of the issued claims. Regarding instant claims 105, 107-108, 110, and the intended or expected results of performing the method at instant claim 88, instantly amended claims 105, 107, 108, and 110 are understood to recite a “wherein” clause expressing the intended and expected results that would necessarily and inherently occur upon the successful completion of the positively recited method steps of amended claim 88, because these claims do not recite nor require additional steps to be performed (see, e.g., MPEP § 2111.04(I)). Accordingly, the intended or expected results of claims 105, 107, 108, and 110 are understood to be fully satisfied by any prior art methodology that requires the active method steps of instant claim 88. Accordingly, claims 105, 107-108, and 110 are rejected for the reasons applied to instant claim 88, above.
The difference: The difference between the issued claims and the instant claims appears to be minor since both claim sets pertain to methods of treating the same or overlapping patient populations by administering the same compound (i.e., avexitide or exendin(9-39)) via the same administration route (subcutaneous) at the same “once daily” concentration (i.e., >60 mg per day), in order to obtain the same basic results, namely the treatment of HH in HH patients following bariatric surgery. The sole difference appears to be that the issued claims are directed to a method of treating patients for an unspecified length of time rather than “at least 14 days” and “30 days or less”.
The answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”8 is “yes”. MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). Here, regarding the difference in duration of treatment, the reference claims a method of treating a patient in need of treatment for HH, and therefore such treatment would be continued for as long as needed9. Therefore, regarding the duration of treatment, the simple repetition of a known step to achieve an art-recognized outcome is “merely the logical result of common sense application of the maxim ‘try, try again’” (see, e.g., Perfect Web Technologies, Inc. v. InfoUSA, Inc. 587 F.3d 1324 (Fed. Cir. Dec. 2, 2009)). In the instant case, an artisan would understand that repeating the reference claim method would predictably lead to the successful treatment of HH in a patient in need thereof, and therefore an artisan would readily appreciate that such steps could be repeated to logically achieve the exact outcome identified in the issued claims, namely treatment of a patient in need of HH treatment. Accordingly, the length of treatment duration could be for any desired time period, such as a clinical trial (i.e., weeks), hospital stay (days or weeks), or potentially over a lifetime. Accordingly, claims directed to the length of treatment do not materially or substantially differentiate the claimed invention relative to the teachings of the prior art. Accordingly, the present claims are directed to obvious variants of the reference claims because it is well-within the ordinary skill in the art to practice claimed methods of treating known conditions in known patient populations by administering known compounds within known therapeutically effective ranges to achieve a known outcome, and to simply repeat such treatment for the duration needed (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (C), (D), and (G), 2144.05(I)). Therefore, the instant claims are directed to obvious variants of the issued claims.
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 variant of the patented 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 88-91, 94, 98-99, 105, 107-108, 110, and 117-119 are rejected.
[NSDP Rejection 04]
Claims 88-91, 94, 99, 105, 107-108, 110, and 117-119 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 10993991 B2. Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Applicable legal analysis: The applicable legal analysis for non-statutory double patenting rejections have been set forth above in a preceding rejection, and that discussion is incorporated herein, but not repeated.
Summary of the pending claim scope: The summary of the pending claim scope has been set forth above in a preceding non-statutory double patenting rejection, and that discussion is incorporated herein, but not repeated.
Regarding instant claim 88, 94, and the treatment of post-bariatric hypoglycemia following gastric bypass, the primary reference claims the treatment of HH following bariatric surgery, including gastric bypass surgery (see, e.g., US’991 at claims 1-10, 15, 17-20). Regarding instant claim 88 and the subcutaneous administration of “at least 60 mg of avexitide” in a single day and in a single injection “once daily”, the reference claims the treatment of the same or overlapping patient population by subcutaneously administering exendin(9-39) (i.e., avexitide) at once or twice daily at 30 mg by subcutaneous administration (see, e.g., US’992 at claims 1, 4-5, 10, 15-16). Accordingly, BID administration of 30 mg would yield 60 mg total in a single day. Regarding instant claims 88, 91, 117-119, and the duration of treatment from a functionally defined minimum number of days (e.g., “a time sufficient to reduce the diurnal percent time…” to “for 30 days or less”, the primary reference claims methods of administration without a specific duration, but for the purpose of treating a patient with HH after bariatric surgery (see, e.g., US’991 at claims 1-10, 15, 17-20). However, per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’991 at col. 18 at lines 51-65), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id). Accordingly, such durations are obvious variants of the claimed method since such duration amounts to the repetition of known steps for 30 days or more as taught for such therapies. Regarding amended claims 88, 117-119, and the treatment of hypoglycemic patients “having glucose values of <70 mg/dL” as measured by CGM, the primary reference is understood to be applicable to patients “in need thereof” of treatment for HH, including in post-bariatric surgery (see, e.g., US’991 at claims 1-10, 15, 17-20), but it does not specifically recite the ranges of “glucose values” as recited at amended claims 88 and 117-119. However, 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)). This is pertinent because “hypoglycemia” is understood as follows:
..where hypoglycemia is defined as a plasma glucose concentration of ≤55 mg/dL by continuous glucose monitoring…
(see, e.g., US’991 at col. 30 at lines 48-53).
Accordingly, “hypoglycemia” necessarily refers to and requires plasma glucose concentrations values at or below under 55 mg/mL (see, e.g., id.). Accordingly, a hypoglycemic patient “in need” of the methods set forth in the issued claims would be readily understood to overlap in scope with the instant recitations at claims 88 and 117-119 (see also MPEP § 2144.05(I), noting 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 89-90, and the volume and concentration limitations, The primary reference recites injections of 30 mg with a concentration of 20 mg/mL (see, e.g., US’991 at claims 1, 10). Accordingly, this concentration range and dosage range encompasses 60 mg total per day, wherein 30 mg is delivered in 1.5 mL. Regarding instant claim 99 and refractory subjects, the primary reference claims a treatment of all HH patients following bariatric surgery, including gastric bypass surgery (see, e.g., Ref at claims 1, 10), which would necessarily encompass any patients at all satisfying such medical requirements, including those that are refractory to other treatments (see id). Accordingly, in view of primary reference, an artisan would treat such patients the same way, whether refractory or not. Therefore, instant claim 99 does not patentably distinguish the claimed invention in view of the issued claims. Regarding instant claims 105, 107-108, 110, and the intended or expected results of performing the method at instant claim 88, instantly amended claims 105, 107, 108, and 110 are understood to recite a “wherein” clause expressing the intended and expected results that would necessarily and inherently occur upon the successful completion of the positively recited method steps of amended claim 88, because these claims do not recite nor require additional steps to be performed (see, e.g., MPEP § 2111.04(I)). Accordingly, the intended or expected results of claims 105, 107, 108, and 110 are understood to be fully satisfied by any prior art methodology that requires the active method steps of instant claim 88. Accordingly, claims 105, 107-108, and 110 are rejected for the reasons applied to instant claim 88, above.
The difference: The difference between the issued claims and the instant claims appears to be minor since both claim sets pertain to methods of treating the same or overlapping patient populations by administering the same compound (i.e., avexitide or exendin(9-39)) via the same administration route (subcutaneous) at “once daily” administration, at therapeutically effective amounts, in order to obtain the same basic results, namely the treatment of HH in HH patients following bariatric surgery. The difference appears to be that the issued claims are directed to a method of treating patients for an unspecified length of time rather than “at least 14 days” and “30 days or less”, and that the issued claims are directed to BID administration of 30 mg twice daily (60 mg total), whereas the instantly amended claims are directed to 60 mg QD.
The answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”10 is “yes”. MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). Here, regarding the difference in duration of treatment, the reference claims a method of treating a patient in need of treatment for HH, and therefore such treatment would be continued for as long as needed11. Therefore, regarding the duration of treatment, the simple repetition of a known step to achieve an art-recognized outcome is “merely the logical result of common sense application of the maxim ‘try, try again’” (see, e.g., Perfect Web Technologies, Inc. v. InfoUSA, Inc. 587 F.3d 1324 (Fed. Cir. Dec. 2, 2009)). In the instant case, an artisan would understand that repeating the reference claim method would predictably lead to the successful treatment of HH in a patient in need thereof, and therefore an artisan would readily appreciate that such steps could be repeated to logically achieve the exact outcome identified in the issued claims, namely treatment of a patient in need of HH treatment. Accordingly, the length of treatment duration could be for any desired time period, such as a clinical trial (i.e., weeks), hospital stay (days or weeks), or potentially over a lifetime. Accordingly, claims directed to the length of treatment do not materially or substantially differentiate the claimed invention relative to the teachings of the prior art. Accordingly, the present claims are directed to obvious variants of the reference claims because it is well-within the ordinary skill in the art to practice claimed methods of treating known conditions in known patient populations by administering known compounds within known therapeutically effective ranges to achieve a known outcome, and to simply repeat such treatment for the duration needed (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (C), (D), and (G), 2144.05(I)). Furthermore, the time between BID dosages is not limited in the issued claims and may be seconds or minutes apart, wherein the QD administration may be administered over 5 or more minutes, and therefore there may be no real difference between the inventions as presently claimed. In addition, in response to the election of species requirement, Applicant made no distinction between 30 mg BID and 60 mg QD, and therefore such species are understood to be obvious variants on record. In addition, or alternatively, per MPEP § 2144.05(II),
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Here, optimization of concentration and dosing frequency is routine in the prior art, and no criticality of range has been shown on record, and therefore an artisan would readily appreciate that the administration of 60 mg BID or QD would lead to a daily administered amount of 60 mg, which would be expected and predicted to treat HH in PBH patients (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2144.05(II)). Therefore, the instant claims are directed to obvious variants of the issued claims.
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 variant of the patented claim.
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 88-91, 94, 99, 105, 107-108, 110, and 117-119 are rejected.
[NSDP Rejection 05]
Claims 88-91, 94, 99, 105, 107-108, 110, and 117-119 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11617782 B2. Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Applicable legal analysis: The applicable legal analysis for non-statutory double patenting rejections have been set forth above in a preceding rejection, and that discussion is incorporated herein, but not repeated.
Summary of the pending claim scope: The summary of the pending claim scope has been set forth above in a preceding non-statutory double patenting rejection, and that discussion is incorporated herein, but not repeated.
Regarding instant claim 88, 94, and the treatment of post-bariatric hypoglycemia following gastric bypass, the primary reference claims the treatment of HH following bariatric surgery, including gastric bypass surgery (see, e.g., US’782 at claims 1, 5, 8-10, 11, 14, 16-19, 20-25). Regarding instant claim 88 and the subcutaneous administration of “at least 60 mg of avexitide” in a single day and in a single injection “once daily”, the reference claims the treatment of the same or overlapping patient population by subcutaneously administering exendin(9-39) (i.e., avexitide) at once or twice daily at 30 mg by subcutaneous administration (see, e.g., US’782 at claims 1, 4-6, 10, 15-16). Accordingly, BID administration of 30 mg would yield 60 mg total in a single day. Regarding instant claims 88, 91, 117-119, and the duration of treatment from a functionally defined minimum number of days (e.g., “a time sufficient to reduce the diurnal percent time…” to “for 30 days or less”, the primary reference claims methods of administration without a specific duration, but for the purpose of treating a patient with HH after bariatric surgery (see, e.g., US’782 at claims 1, 4-6, 10, 15-16). However, per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’782 at cols. 18-19 at bridging ¶), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id). Accordingly, such durations are obvious variants of the claimed method since such duration amounts to the repetition of known steps for 30 days or more as taught for such therapies. Regarding amended claims 88, 117-119, and the treatment of hypoglycemic patients “having glucose values of <70 mg/dL” as measured by CGM, the primary reference is understood to be applicable to patients “in need thereof” of treatment for HH, including in post-bariatric surgery (see, e.g., US’782 at claims 1, 4-6, 10, 15-16), but it does not specifically recite the ranges of “glucose values” as recited at amended claims 88 and 117-119. However, 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)). This is pertinent because “hypoglycemia” is understood as follows:
..hypoglycemia is defined as a plasma glucose concentration of ≤55 mg/dL by continuous glucose monitoring…
(see, e.g., US’782 at col. 31 at lines 10-16).
Accordingly, “hypoglycemia” necessarily refers to and requires plasma glucose concentrations values at or below under 55 mg/mL (see, e.g., id.). Accordingly, a hypoglycemic patient “in need” of the methods set forth in the issued claims would be readily understood to overlap in scope with the instant recitations at claims 88 and 117-119 (see also MPEP § 2144.05(I), noting 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 89-90, and the volume and concentration limitations, The primary reference recites injections of 30 mg with a concentration of 20 mg/mL (see, e.g., US’782 at claims 1, 5-6, 10). Accordingly, this concentration range and dosage range encompasses 60 mg total per day, wherein 30 mg is delivered in 1.5 mL. Regarding instant claim 99 and refractory subjects, the primary reference claims a treatment of all HH patients following bariatric surgery, including gastric bypass surgery (see, e.g., Ref at claims 1, 10), which would necessarily encompass any patients at all satisfying such medical requirements, including those that are refractory to other treatments (see id). Accordingly, in view of primary reference, an artisan would treat such patients the same way, whether refractory or not. Therefore, instant claim 99 does not patentably distinguish the claimed invention in view of the issued claims. Regarding instant claims 105, 107-108, 110, and the intended or expected results of performing the method at instant claim 88, instantly amended claims 105, 107, 108, and 110 are understood to recite a “wherein” clause expressing the intended and expected results that would necessarily and inherently occur upon the successful completion of the positively recited method steps of amended claim 88, because these claims do not recite nor require additional steps to be performed (see, e.g., MPEP § 2111.04(I)). Accordingly, the intended or expected results of claims 105, 107, 108, and 110 are understood to be fully satisfied by any prior art methodology that requires the active method steps of instant claim 88. Accordingly, claims 105, 107-108, and 110 are rejected for the reasons applied to instant claim 88, above.
The difference: The difference between the issued claims and the instant claims appears to be minor since both claim sets pertain to methods of treating the same or overlapping patient populations by administering the same compound (i.e., avexitide or exendin(9-39)) via the same administration route (subcutaneous) at “once daily” administration, at therapeutically effective amounts, in order to obtain the same basic results, namely the treatment of HH in HH patients following bariatric surgery. The difference appears to be that the issued claims are directed to a method of treating patients for an unspecified length of time rather than “at least 14 days” and “30 days or less”, and that the issued claims are directed to BID administration of 30 mg twice daily (60 mg total), whereas the instantly amended claims are directed to 60 mg QD.
The answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”12 is “yes”. MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). Here, regarding the difference in duration of treatment, the reference claims a method of treating a patient in need of treatment for HH, and therefore such treatment would be continued for as long as needed13. Therefore, regarding the duration of treatment, the simple repetition of a known step to achieve an art-recognized outcome is “merely the logical result of common sense application of the maxim ‘try, try again’” (see, e.g., Perfect Web Technologies, Inc. v. InfoUSA, Inc. 587 F.3d 1324 (Fed. Cir. Dec. 2, 2009)). In the instant case, an artisan would understand that repeating the reference claim method would predictably lead to the successful treatment of HH in a patient in need thereof, and therefore an artisan would readily appreciate that such steps could be repeated to logically achieve the exact outcome identified in the issued claims, namely treatment of a patient in need of HH treatment. Accordingly, the length of treatment duration could be for any desired time period, such as a clinical trial (i.e., weeks), hospital stay (days or weeks), or potentially over a lifetime. Accordingly, claims directed to the length of treatment do not materially or substantially differentiate the claimed invention relative to the teachings of the prior art. Accordingly, the present claims are directed to obvious variants of the reference claims because it is well-within the ordinary skill in the art to practice claimed methods of treating known conditions in known patient populations by administering known compounds within known therapeutically effective ranges to achieve a known outcome, and to simply repeat such treatment for the duration needed (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (C), (D), and (G), 2144.05(I)). Furthermore, the time between BID dosages is not limited in the issued claims and may be seconds or minutes apart, wherein the QD administration may be administered over 5 or more minutes, and therefore there may be no real difference between the inventions as presently claimed. In addition, in response to the election of species requirement, Applicant made no distinction between 30 mg BID and 60 mg QD, and therefore such species are understood to be obvious variants on record. In addition, or alternatively, per MPEP § 2144.05(II),
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Here, optimization of concentration and dosing frequency is routine in the prior art, and no criticality of range has been shown on record, and therefore an artisan would readily appreciate that the administration of 60 mg BID or QD would lead to a daily administered amount of 60 mg, which would be expected and predicted to treat HH in PBH patients (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2144.05(II)). Therefore, the instant claims are directed to obvious variants of the issued claims.
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 variant of the patented 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 88-91, 94, 99, 105, 107-108, 110, and 117-119 are rejected.
[NSDP Rejection 06]
Claims 88-91, 94, 98-99, 105, 107-108, 110, and 117-119 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11622995 B2. Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Applicable legal analysis: The applicable legal analysis for non-statutory double patenting rejections have been set forth above in a preceding rejection, and that discussion is incorporated herein, but not repeated.
Summary of the pending claim scope: The summary of the pending claim scope has been set forth above in a preceding non-statutory double patenting rejection, and that discussion is incorporated herein, but not repeated.
Regarding instant claim 88, 94, and the treatment of post-bariatric hypoglycemia following gastric bypass, the primary reference claims the treatment of HH following bariatric surgery, including gastric bypass surgery (see, e.g., US’995 at claims 1, 7-11, 16-20, 22-25). Regarding instant claim 88 and the subcutaneous administration of “at least 60 mg of avexitide” in a single day and in a single injection “once daily”, the reference claims the treatment of the same or overlapping patient population by subcutaneously administering exendin(9-39) (i.e., avexitide) at the overlapping range of 2-100 mg by subcutaneous administration “once per day” (see, e.g., US’995 at claims 1, 5, 11, 14). Regarding instant claims 88, 91, 117-119, and the duration of treatment from a functionally defined minimum number of days (e.g., “a time sufficient to reduce the diurnal percent time…” to “for 30 days or less”, the primary reference claims methods of administration without a specific duration, but for the purpose of treating a patient with HH after bariatric surgery (see, e.g., US’995 at claims 1, 7-11, 16-20, 22-25). However, per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’995 at col. 24 at line 60 to col. 25 at line 9), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id). Accordingly, such durations are obvious variants of the claimed method since such duration amounts to the repetition of known steps for 30 days or more as taught for such therapies. Regarding amended claims 88, 117-119, and the treatment of hypoglycemic patients “having glucose values of <70 mg/dL” as measured by CGM, the primary reference is understood to be applicable to patients “in need thereof” of treatment for HH, including in post-bariatric surgery (see, e.g., US’995 at claims 1, 7-11, 16-20, 22-25), but it does not specifically recite the ranges of “glucose values” as recited at amended claims 88 and 117-119. However, 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)). This is pertinent because “hypoglycemia” is understood as follows:
..hypoglycemia is defined as a plasma glucose concentration of ≤55 mg/dL by continuous glucose monitoring…
(see, e.g., US’995 at col. 38 at lines 60-65).
Accordingly, “hypoglycemia” necessarily refers to and requires plasma glucose concentrations values at or below under 55 mg/mL (see, e.g., id.). Accordingly, a hypoglycemic patient “in need” of the methods set forth in the issued claims would be readily understood to overlap in scope with the instant recitations at claims 88 and 117-119 (see also MPEP § 2144.05(I), noting 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 89-90, 98, and the volume and concentration limitations, the primary reference recites “once per day” injections of 2-100 mg with a concentration of 45 mg/mL (see, e.g., US’995 at claims 1-2, 5, 11, 14). Accordingly, this concentration range and dosage range encompasses at least once daily 60 mg delivered at least at 1.334 mL. Regarding instant claim 99 and refractory subjects, the primary reference claims a treatment of all HH patients following bariatric surgery, including gastric bypass surgery (see, e.g., Ref at claims 1-5), which would necessarily encompass any patients at all satisfying such medical requirements, including those that are refractory to other treatments (see id). Accordingly, in view of primary reference, an artisan would treat such patients the same way, whether refractory or not. Therefore, instant claim 99 does not patentably distinguish the claimed invention in view of the issued claims. Regarding instant claims 105, 107-108, 110, and the intended or expected results of performing the method at instant claim 88, instantly amended claims 105, 107, 108, and 110 are understood to recite a “wherein” clause expressing the intended and expected results that would necessarily and inherently occur upon the successful completion of the positively recited method steps of amended claim 88, because these claims do not recite nor require additional steps to be performed (see, e.g., MPEP § 2111.04(I)). Accordingly, the intended or expected results of claims 105, 107, 108, and 110 are understood to be fully satisfied by any prior art methodology that requires the active method steps of instant claim 88. Accordingly, claims 105, 107-108, and 110 are rejected for the reasons applied to instant claim 88, above.
The difference: The difference between the issued claims and the instant claims appears to be minor since both claim sets pertain to methods of treating the same or overlapping patient populations by administering the same compound (i.e., avexitide or exendin(9-39)) via the same administration route (subcutaneous) at the same “once daily” concentration (i.e., >60 mg per day), in order to obtain the same basic results, namely the treatment of HH in HH patients following bariatric surgery. The sole difference appears to be that the issued claims are directed to a method of treating patients for an unspecified length of time rather than “at least 14 days” and “30 days or less”.
The answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”14 is “yes”. MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). Here, regarding the difference in duration of treatment, the reference claims a method of treating a patient in need of treatment for HH, and therefore such treatment would be continued for as long as needed15. Therefore, regarding the duration of treatment, the simple repetition of a known step to achieve an art-recognized outcome is “merely the logical result of common sense application of the maxim ‘try, try again’” (see, e.g., Perfect Web Technologies, Inc. v. InfoUSA, Inc. 587 F.3d 1324 (Fed. Cir. Dec. 2, 2009)). In the instant case, an artisan would understand that repeating the reference claim method would predictably lead to the successful treatment of HH in a patient in need thereof, and therefore an artisan would readily appreciate that such steps could be repeated to logically achieve the exact outcome identified in the issued claims, namely treatment of a patient in need of HH treatment. Accordingly, the length of treatment duration could be for any desired time period, such as a clinical trial (i.e., weeks), hospital stay (days or weeks), or potentially over a lifetime. Accordingly, claims directed to the length of treatment do not materially or substantially differentiate the claimed invention relative to the teachings of the prior art. Accordingly, the present claims are directed to obvious variants of the reference claims because it is well-within the ordinary skill in the art to practice claimed methods of treating known conditions in known patient populations by administering known compounds within known therapeutically effective ranges to achieve a known outcome, and to simply repeat such treatment for the duration needed (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (C), (D), and (G), 2144.05(I)). Therefore, the instant claims are directed to obvious variants of the issued claims.
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, patentably indistinct variant of the patent 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 88-91, 94, 98-99, 105, 107-108, 110, and 117-119 are rejected.
[NSDP Rejection 07]
Claims 88-91, 94, 98-99, 105, 107-108, 110, and 117-119 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12102663 B2. Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Applicable legal analysis: The applicable legal analysis for non-statutory double patenting rejections have been set forth above in a preceding rejection, and that discussion is incorporated herein, but not repeated.
Summary of the pending claim scope: The summary of the pending claim scope has been set forth above in a preceding non-statutory double patenting rejection, and that discussion is incorporated herein, but not repeated.
Regarding instant claim 88, 94, and the treatment of post-bariatric hypoglycemia following gastric bypass, the primary reference claims the treatment of HH following bariatric surgery, including gastric bypass surgery (see, e.g., US’663 at claims 1, 4-8, 9, 11-15). Regarding instant claim 88 and the subcutaneous administration of “at least 60 mg of avexitide” in a single day and in a single injection “once daily”, the primary reference claims the treatment of HH by subcutaneously administering a functionally defined therapeutically effective Avexitide, which may be administered once daily (QD) or twice daily (BID) (see, e.g., US’663 at claims 1, 4, 9, 11, 16). The use of a functional definition raises claim interpretation issues (i.e., what amount of Avexitide is enough to achieve the functionally claimed result of a “Cmax of at least 100 ng/ml”?). 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, the functionally defined “therapeutically effective” amount is reasonably inferred to be at least 10-30 mg, wherein 30 mg twice daily is 60 mg per day. Furthermore, the open-ended range of “at least 100 ng/ml” covers the range of ≥100ng/ml; this is pertinent because 10-30 mg would be reasonably expected to represent the minimum amount required to obtain 100 ng/ml; therefore, the functionally defined range at issued claims 1 and 9 of US’633 is reasonably inferred to encompass the entire range of “more than at least” 10-30 mg, or ≥10mg and ≥30 mg of exendin(9-39). Accordingly, in view of the functionally defined “therapeutically effective amount” in the issued claims of US’663, the claims are reasonably inferred to read upon any values of exendin(9-39) that are ≥30 mg/mL, which would include 60 mg or more. Accordingly, the instant claims do not clearly and unambiguously patentably distinguish the claimed invention over the issued claims of US’663 for once daily administration. Regarding instant claims 88, 91, 117-119, and the duration of treatment from a functionally defined minimum number of days (e.g., “a time sufficient to reduce the diurnal percent time…” to “for 30 days or less”, the primary reference claims methods of administration without a specific duration, but for the purpose of treating a patient with HH after bariatric surgery (see, e.g., US’663 at claims 1, 4-8, 9, 11-15). However, per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’663 at col. 19 at lines 5 to line 18), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id). Accordingly, such durations are obvious variants of the claimed method since such duration amounts to the repetition of known steps for 30 days or more as taught for such therapies. Regarding amended claims 88, 117-119, and the treatment of hypoglycemic patients “having glucose values of <70 mg/dL” as measured by CGM, the primary reference is understood to be applicable to patients “in need thereof” of treatment for HH, including in post-bariatric surgery (see, e.g., US’663 at claims 1, 4-8, 9, 11-15), but it does not specifically recite the ranges of “glucose values” as recited at amended claims 88 and 117-119. However, 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)). This is pertinent because “hypoglycemia” is understood as follows:
..hypoglycemia is defined as a plasma glucose concentration of ≤55 mg/dL by continuous glucose monitoring…
(see, e.g., US’663 at col. 30 at lines 48-55).
Accordingly, “hypoglycemia” necessarily refers to and requires plasma glucose concentrations values at or below under 55 mg/mL (see, e.g., id.). Accordingly, a hypoglycemic patient “in need” of the methods set forth in the issued claims would be readily understood to overlap in scope with the instant recitations at claims 88 and 117-119 (see also MPEP § 2144.05(I), noting 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 claim 89-90, 98, and the volume and concentration limitations, the primary reference is reasonably understood to recite “once per day” subcutaneous injections of ≥30 mg of exendin(9-39) as explained above. Critically, although such administration must necessarily and inherently have a concentration and a volume, such parameters are not explicitly recited in the claim. 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)) and to use the specification to identify obvious variants (see, e.g., MPEP § 804(II)(B)(1), explaining that “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”). Here, the implied obvious variations of volume in portions providing support for the reference claims of claims 1 and 3 would include obvious variants of concentrations of up to at least 45 mg/ml (see, e.g., US’633 at col 14 at lines 4-10), which for a 60 mg dose would require a volume of 1.334 mL. Accordingly, although not explicitly claimed, a volume and a concentration are inherent properties of the claimed invention, and per MPEP § 804(II)(B)(1), the definitions and obvious variations may be considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application. Here, such differences amount to obvious variations of the issued claims of US’663. Regarding instant claim 99 and refractory subjects, the primary reference claims a treatment of all HH patients following bariatric surgery, including gastric bypass surgery (see, e.g., Ref at claims 1, 4-8, 9, 11-15), which would necessarily encompass any patients at all satisfying such medical requirements, including those that are refractory to other treatments (see id). Accordingly, in view of primary reference, an artisan would treat such patients the same way, whether refractory or not. Therefore, instant claim 99 does not patentably distinguish the claimed invention in view of the issued claims. Regarding instant claims 105, 107-108, 110, and the intended or expected results of performing the method at instant claim 88, instantly amended claims 105, 107, 108, and 110 are understood to recite a “wherein” clause expressing the intended and expected results that would necessarily and inherently occur upon the successful completion of the positively recited method steps of amended claim 88, because these claims do not recite nor require additional steps to be performed (see, e.g., MPEP § 2111.04(I)). Accordingly, the intended or expected results of claims 105, 107, 108, and 110 are understood to be fully satisfied by any prior art methodology that requires the active method steps of instant claim 88. Accordingly, claims 105, 107-108, and 110 are rejected for the reasons applied to instant claim 88, above.
The difference: The difference between the issued claims and the instant claims appears to be minor since both claim sets pertain to methods of treating the same or overlapping patient populations by administering the same compound (i.e., avexitide or exendin(9-39)) via the same administration route (subcutaneous) at the same “once daily” concentration (i.e., >60 mg per day), in order to obtain the same basic results, namely the treatment of HH in HH patients following bariatric surgery. The sole difference appears to be that the issued claims are directed to a method of treating patients for an unspecified length of time rather than “at least 14 days” and “30 days or less”.
The answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”16 is “yes”. MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). Here, regarding the difference in duration of treatment, the reference claims a method of treating a patient in need of treatment for HH, and therefore such treatment would be continued for as long as needed17. Therefore, regarding the duration of treatment, the simple repetition of a known step to achieve an art-recognized outcome is “merely the logical result of common sense application of the maxim ‘try, try again’” (see, e.g., Perfect Web Technologies, Inc. v. InfoUSA, Inc. 587 F.3d 1324 (Fed. Cir. Dec. 2, 2009)). In the instant case, an artisan would understand that repeating the reference claim method would predictably lead to the successful treatment of HH in a patient in need thereof, and therefore an artisan would readily appreciate that such steps could be repeated to logically achieve the exact outcome identified in the issued claims, namely treatment of a patient in need of HH treatment. Accordingly, the length of treatment duration could be for any desired time period, such as a clinical trial (i.e., weeks), hospital stay (days or weeks), or potentially over a lifetime. Accordingly, claims directed to the length of treatment do not materially or substantially differentiate the claimed invention relative to the teachings of the prior art. Accordingly, the present claims are directed to obvious variants of the reference claims because it is well-within the ordinary skill in the art to practice claimed methods of treating known conditions in known patient populations by administering known compounds within known therapeutically effective ranges to achieve a known outcome, and to simply repeat such treatment for the duration needed (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (C), (D), and (G), 2144.05(I)). Therefore, the instant claims are directed to obvious variants of the issued claims.
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, patentably indistinct variant of the patent 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 88-91, 94, 98-99, 105, 107-108, 110, and 117-119 are rejected.
[NSDP Rejection 08]
Claims 88-91, 94, 98-99, 105, 107-108, 110, and 117-119 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11020484 B2. Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Applicable legal analysis: The applicable legal analysis for non-statutory double patenting rejections have been set forth above in a preceding rejection, and that discussion is incorporated herein, but not repeated.
Summary of the pending claim scope: The summary of the pending claim scope has been set forth above in a preceding non-statutory double patenting rejection, and that discussion is incorporated herein, but not repeated.
Regarding instant claim 88, 94, and the treatment of post-bariatric hypoglycemia following gastric bypass, the primary reference claims the treatment of HH following bariatric surgery (see, e.g., US’484 at claims 21-30). Regarding instant claim 88 and the subcutaneous administration of “at least 60 mg of avexitide” in a single day and in a single injection “once daily”, the reference claims the treatment of the same or overlapping patient population by subcutaneously administering exendin(9-39) (i.e., avexitide) at a dosage of “about 30 mg to about 75 mg once daily (QD)” and at “90 mg QD” (see, e.g., US’484 at claims 21-25). Regarding instant claims 88, 91, 117-119, and the duration of treatment from a functionally defined minimum number of days (e.g., “a time sufficient to reduce the diurnal percent time…” to “for 30 days or less”, the primary reference claims methods of administration without a specific duration, but for the purpose of treating a patient with HH after bariatric surgery (see, e.g., US’484 at claims 21-30). However, per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’484 at col. 18 at lines 50-60), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id). Accordingly, such durations are obvious variants of the claimed method since such duration amounts to the repetition of known steps for 30 days or more as taught for such therapies. Regarding amended claims 88, 117-119, and the treatment of hypoglycemic patients “having glucose values of <70 mg/dL” as measured by CGM, the primary reference is understood to be applicable to patients “in need thereof” of treatment for HH, including in post-bariatric surgery (see, e.g., US’484 at claims 21-30), but it does not specifically recite the ranges of “glucose values” as recited at amended claims 88 and 117-119. However, 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)). This is pertinent because “hypoglycemia” is understood as follows:
..hypoglycemia is defined as a plasma glucose concentration of ≤54 mg/dL by …continuous glucose monitoring…
(see, e.g., US’484 at col. 14 at lines 25-31).
Accordingly, “hypoglycemia” necessarily refers to and requires plasma glucose concentrations values at or below under 55 mg/mL (see, e.g., id.). Accordingly, a hypoglycemic patient “in need” of the methods set forth in the issued claims would be readily understood to overlap in scope with the instant recitations at claims 88 and 117-119 (see also MPEP § 2144.05(I), noting 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 89-90, 98, and the volume and concentration limitations, the primary reference recites and claims injections with a concentration of “about 10 mg/ml to about 120 mg/ml”, including 45 mg/mL and 90 mg/ml (see, e.g., US’484 at claim 13, 27-28). Accordingly, and artisan would readily appreciate that 75 mg or 90 mg QD treatment for post-bariatric HH (see, e.g., US’484 at claims 21-25) could be administered at a concentration of “about 10 mg/ml to about 120 mg/ml”, including 45 mg/mL and 90 mg/ml (see, e.g., US’484 at claim 13, 27-28), which would imply a volume of ≤1 ml. Regarding instant claim 99 and refractory subjects, the primary reference claims a treatment of all HH patients following bariatric surgery (see, e.g., Ref at claims 21-23), which would necessarily encompass any patients at all satisfying such medical requirements, including those that are refractory to other treatments (see id). Accordingly, in view of primary reference, an artisan would treat such patients the same way, whether refractory or not. Therefore, instant claim 99 does not patentably distinguish the claimed invention in view of the issued claims. Regarding instant claims 105, 107-108, 110, and the intended or expected results of performing the method at instant claim 88, instantly amended claims 105, 107, 108, and 110 are understood to recite a “wherein” clause expressing the intended and expected results that would necessarily and inherently occur upon the successful completion of the positively recited method steps of amended claim 88, because these claims do not recite nor require additional steps to be performed (see, e.g., MPEP § 2111.04(I)). Accordingly, the intended or expected results of claims 105, 107, 108, and 110 are understood to be fully satisfied by any prior art methodology that requires the active method steps of instant claim 88. Accordingly, claims 105, 107-108, and 110 are rejected for the reasons applied to instant claim 88, above.
The difference: The difference between the issued claims and the instant claims appears to be minor since both claim sets pertain to methods of treating the same or overlapping patient populations by administering the same compound (i.e., avexitide or exendin(9-39)) via the same administration route (subcutaneous) at the same “once daily” concentration (i.e., 75 or 90 mg per day), in order to obtain the same basic results, namely the treatment of HH in HH patients following bariatric surgery. The sole difference appears to be that the issued claims are directed to a method of treating patients for an unspecified length of time rather than “at least 14 days” and “30 days or less”.
The answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”18 is “yes”. MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). Here, regarding the difference in duration of treatment, the reference claims a method of treating a patient in need of treatment for HH, and therefore such treatment would be continued for as long as needed19. Therefore, regarding the duration of treatment, the simple repetition of a known step to achieve an art-recognized outcome is “merely the logical result of common sense application of the maxim ‘try, try again’” (see, e.g., Perfect Web Technologies, Inc. v. InfoUSA, Inc. 587 F.3d 1324 (Fed. Cir. Dec. 2, 2009)). In the instant case, an artisan would understand that repeating the reference claim method would predictably lead to the successful treatment of HH in a patient in need thereof, and therefore an artisan would readily appreciate that such steps could be repeated to logically achieve the exact outcome identified in the issued claims, namely treatment of a patient in need of HH treatment. Accordingly, the length of treatment duration could be for any desired time period, such as a clinical trial (i.e., weeks), hospital stay (days or weeks), or potentially over a lifetime. Accordingly, claims directed to the length of treatment do not materially or substantially differentiate the claimed invention relative to the teachings of the prior art. Accordingly, the present claims are directed to obvious variants of the reference claims because it is well-within the ordinary skill in the art to practice claimed methods of treating known conditions in known patient populations by administering known compounds within known therapeutically effective ranges to achieve a known outcome, and to simply repeat such treatment for the duration needed (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (C), (D), and (G), 2144.05(I)). Therefore, the instant claims are directed to obvious variants of the issued claims.
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, patentably indistinct variant of the patent 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 88-91, 94, 98-99, 105, 107-108, 110, and 117-119 are rejected.
[NSDP Rejection 09]
Claims 88-91, 94, 98-99, 105, 107-108, 110, and 117-119 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11738086 B2. Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Applicable legal analysis: The applicable legal analysis for non-statutory double patenting rejections have been set forth above in a preceding rejection, and that discussion is incorporated herein, but not repeated.
Summary of the pending claim scope: The summary of the pending claim scope has been set forth above in a preceding non-statutory double patenting rejection, and that discussion is incorporated herein, but not repeated.
Regarding instant claim 88, 94, and the treatment of post-bariatric hypoglycemia following gastric bypass, the primary reference claims the treatment of HH following bariatric surgery (see, e.g., US’086 at claims 1, 6-7, 23). Regarding instant claim 88 and the subcutaneous administration of “at least 60 mg of avexitide” in a single day and in a single injection “once daily”, the reference claims the treatment of the same or overlapping patient population by subcutaneously administering exendin(9-39) (i.e., avexitide) at a dosage of 75 mg and up to about 90 mg, once per day (QD) (see, e.g., US’086 at claims 1-4, 23). Regarding instant claims 88, 91, 117-119, and the duration of treatment from a functionally defined minimum number of days (e.g., “a time sufficient to reduce the diurnal percent time…” to “for 30 days or less”, the primary reference claims methods of administration without a specific duration, but for the purpose of treating a patient with HH after bariatric surgery (see, e.g., US’086 at claims 1-4, 6-7, 23). However, per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’086 at col. 18 at lines 50-60), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id). Accordingly, such durations are obvious variants of the claimed method since such duration amounts to the repetition of known steps for 30 days or more as taught for such therapies. Regarding amended claims 88, 117-119, and the treatment of hypoglycemic patients “having glucose values of <70 mg/dL” as measured by CGM, the primary reference is understood to be applicable to patients “in need thereof” of treatment for HH, including in post-bariatric surgery (see, e.g., US’086 at claims 1-4, 6-7, 23), but it does not specifically recite the ranges of “glucose values” as recited at amended claims 88 and 117-119. However, 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)). This is pertinent because “hypoglycemia” is understood as follows:
..hypoglycemia is defined as a plasma glucose concentration of ≤54 mg/dL by …continuous glucose monitoring…
(see, e.g., US’086 at col. 14 at lines 25-31).
Accordingly, “hypoglycemia” necessarily refers to and requires plasma glucose concentrations values at or below under 55 mg/mL (see, e.g., id.). Accordingly, a hypoglycemic patient “in need” of the methods set forth in the issued claims would be readily understood to overlap in scope with the instant recitations at claims 88 and 117-119 (see also MPEP § 2144.05(I), noting 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 89-90, 98, and the volume and concentration limitations, the primary reference recites and claims injections with a concentration of “about 10 mg/ml to about 120 mg/ml”, a concentration of “at least 15 mg/ml” and “about 60 mg/ml” (see, e.g., US’086 at claims 19-22). Accordingly, a 90 mg dosage at 60 mg/ml would be 1.5 mL, and a 90 mg dosage at a 120 mg/ml would be a volume of ≤1 ml. Regarding instant claim 99 and refractory subjects, the primary reference claims a treatment of all HH patients following bariatric surgery (see, e.g., Ref at claims 1, 6-7), which would necessarily encompass any patients at all satisfying such medical requirements, including those that are refractory to other treatments (see id). Accordingly, in view of primary reference, an artisan would treat such patients the same way, whether refractory or not. Therefore, instant claim 99 does not patentably distinguish the claimed invention in view of the issued claims. Regarding instant claims 105, 107-108, 110, and the intended or expected results of performing the method at instant claim 88, instantly amended claims 105, 107, 108, and 110 are understood to recite a “wherein” clause expressing the intended and expected results that would necessarily and inherently occur upon the successful completion of the positively recited method steps of amended claim 88, because these claims do not recite nor require additional steps to be performed (see, e.g., MPEP § 2111.04(I)). Accordingly, the intended or expected results of claims 105, 107, 108, and 110 are understood to be fully satisfied by any prior art methodology that requires the active method steps of instant claim 88. Accordingly, claims 105, 107-108, and 110 are rejected for the reasons applied to instant claim 88, above.
The difference: The difference between the issued claims and the instant claims appears to be minor since both claim sets pertain to methods of treating the same or overlapping patient populations by administering the same compound (i.e., avexitide or exendin(9-39)) via the same administration route (subcutaneous) at the same “once daily” concentration (i.e., 90 mg per day), in order to obtain the same basic results, namely the treatment of HH in HH patients following bariatric surgery. The sole difference appears to be that the issued claims are directed to a method of treating patients for an unspecified length of time rather than “at least 14 days” and “30 days or less”.
The answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”20 is “yes”. MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). Here, regarding the difference in duration of treatment, the reference claims a method of treating a patient in need of treatment for HH, and therefore such treatment would be continued for as long as needed21. Therefore, regarding the duration of treatment, the simple repetition of a known step to achieve an art-recognized outcome is “merely the logical result of common sense application of the maxim ‘try, try again’” (see, e.g., Perfect Web Technologies, Inc. v. InfoUSA, Inc. 587 F.3d 1324 (Fed. Cir. Dec. 2, 2009)). In the instant case, an artisan would understand that repeating the reference claim method would predictably lead to the successful treatment of HH in a patient in need thereof, and therefore an artisan would readily appreciate that such steps could be repeated to logically achieve the exact outcome identified in the issued claims, namely treatment of a patient in need of HH treatment. Accordingly, the length of treatment duration could be for any desired time period, such as a clinical trial (i.e., weeks), hospital stay (days or weeks), or potentially over a lifetime. Accordingly, claims directed to the length of treatment do not materially or substantially differentiate the claimed invention relative to the teachings of the prior art. Accordingly, the present claims are directed to obvious variants of the reference claims because it is well-within the ordinary skill in the art to practice claimed methods of treating known conditions in known patient populations by administering known compounds within known therapeutically effective ranges to achieve a known outcome, and to simply repeat such treatment for the duration needed (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (C), (D), and (G), 2144.05(I)). Therefore, the instant claims are directed to obvious variants of the issued claims.
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, patentably indistinct variant of the patent 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 88-91, 94, 98-99, 105, 107-108, 110, and 117-119 are rejected.
[Provisional NSDP Rejection 01]
Claims 88-91, 94, 98-99, 105, 107-108, 110 and 117-119 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, 13-14, 32-40 of copending Application No. 18/745,091 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other as discussed below.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Applicable legal analysis: The applicable legal analysis for non-statutory double patenting rejections have been set forth above in a preceding rejection, and that discussion is incorporated herein, but not repeated.
Summary of the pending claim scope: The summary of the pending claim scope has been set forth above in a preceding non-statutory double patenting rejection, and that discussion is incorporated herein, but not repeated.
Regarding instant claim 88, 94, and the treatment of post-bariatric hypoglycemia following gastric bypass, the primary reference claims the treatment of HH following bariatric surgery (see, e.g., App’091 at claims 1, 32, 33-36). Regarding instant claim 88 and the subcutaneous administration of “at least 60 mg of avexitide” in a single day and in a single injection “once daily”, the reference claims the treatment of the same or overlapping patient population by subcutaneously administering exendin(9-39) (i.e., avexitide) at once daily (see, e.g., App’091 at claims 1, 32, 33-36). Notably the primary reference claims the treatment of HH by subcutaneously administering a functionally defined therapeutically effective Avexitide, which may be administered once daily (QD) (see, e.g., App’091 at claim 1 and 10, wherein claim 1 is any “therapeutically effective amount” and claim 10 recites an amount that results in “at least 100 ng/ml concentration”). The use of a functional definition raises claim interpretation issues (i.e., what amount of Avexitide constitutes a “therapeutically effective amount” or otherwise constitutes an amount sufficient to meet or exceed the minimal concentration recited at claim 10?). 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, the functionally defined “therapeutically effective” that is capable of achieving any range at dependent claim 10 that is capable of achieving “at least 100 ng/ml concentration”, is understood to be the entire range of “more than at least” 10-30 mg, or ≥10mg and ≥30 mg of exendin(9-39). Accordingly, in view of the functionally defined “therapeutically effective amount” and limitations of claim 10, in the pending claims of App’091, the claims are reasonably inferred to read upon any values of exendin(9-39) that are ≥30 mg/mL, which would include 60 mg or more. Accordingly, the instant claims do not clearly and unambiguously patentably distinguish the claimed invention over the copending claims of App’091 for once daily administration. Regarding instant claims 88, 91, 117-119, and the duration of treatment from a functionally defined minimum number of days (e.g., “a time sufficient to reduce the diurnal percent time…” to “for 30 days or less”, the primary reference claims methods of administration without a specific duration, but for the purpose of treating a patient with HH after bariatric surgery (see, e.g., App’091 at claims 1, 32, 33-36). However, per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., App’091 at Spec. filed 6/17/2024 at ¶[0105]), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id). Accordingly, such durations are obvious variants of the claimed method since such duration amounts to the repetition of known steps for 30 days or more as taught for such therapies. Regarding amended claims 88, 117-119, and the treatment of hypoglycemic patients “having glucose values of <70 mg/dL” as measured by CGM, the primary reference is understood to be applicable to patients “in need thereof” of treatment for HH, including in post-bariatric surgery (see, e.g., App’091 at claims 1, 32, 33-36), but it does not specifically recite the ranges of “glucose values” as recited at amended claims 88 and 117-119. However, 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)). This is pertinent because “hypoglycemia” is understood as follows:
..hypoglycemia is defined as a plasma glucose concentration of ≤55 mg/dL by continuous glucose monitoring…
(see, e.g., App’091 at Spec. filed 6/17/2024 at ¶[0158]).
Accordingly, “hypoglycemia” necessarily refers to and requires plasma glucose concentrations values at or below under 55 mg/mL (see, e.g., id.). Accordingly, a hypoglycemic patient “in need” of the methods set forth in the issued claims would be readily understood to overlap in scope with the instant recitations at claims 88 and 117-119 (see also MPEP § 2144.05(I), noting 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 89-90, 98, and the volume and concentration limitations, as explained above, the “therapeutically effective amount” defined by claims 1 and 10 are understood to include any amount ≥30 mg/mL, which would include 60 mg or more. This is pertinent because claim 1 of App’091 limits the volume to 0.25 mL to 2 mL, which overlaps in scope with instant claim 98. Furthermore, because the claim scope includes all values ≥30 mg/mL, this means that amounts such as 60 mg at 60mg/mL are reasonably understood to be fully encompassed by the claims of App’091. Regarding instant claim 99 and refractory subjects, the primary reference claims a treatment of all HH patients following bariatric surgery (see, e.g., Ref at claims 1, 10, 32-36), which would necessarily encompass any patients at all satisfying such medical requirements, including those that are refractory to other treatments (see id). Accordingly, in view of primary reference, an artisan would treat such patients the same way, whether refractory or not. Therefore, instant claim 99 does not patentably distinguish the claimed invention in view of the issued claims. Regarding instant claim 103 and eating a meal within 90 minutes of a dosage, the primary reference explicitly claims administration within ~60 minutes of a morning meal (see, e.g., App’091 at claims 13-14). Regarding instant claims 105, 107-108, 110, and the intended or expected results of performing the method at instant claim 88, instantly amended claims 105, 107, 108, and 110 are understood to recite a “wherein” clause expressing the intended and expected results that would necessarily and inherently occur upon the successful completion of the positively recited method steps of amended claim 88, because these claims do not recite nor require additional steps to be performed (see, e.g., MPEP § 2111.04(I)). Accordingly, the intended or expected results of claims 105, 107, 108, and 110 are understood to be fully satisfied by any prior art methodology that requires the active method steps of instant claim 88. Accordingly, claims 105, 107-108, and 110 are rejected for the reasons applied to instant claim 88, above.
The difference: The difference between the issued claims and the instant claims appears to be minor since both claim sets pertain to methods of treating the same or overlapping patient populations by administering the same compound (i.e., avexitide or exendin(9-39)) via the same administration route (subcutaneous) at the same “once daily” concentration (i.e., 90 mg per day), in order to obtain the same basic results, namely the treatment of HH in HH patients following bariatric surgery. The sole difference appears to be that the issued claims are directed to a method of treating patients for an unspecified length of time rather than “at least 14 days” and “30 days or less”.
The answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”22 is “yes”. MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). Here, regarding the difference in duration of treatment, the reference claims a method of treating a patient in need of treatment for HH, and therefore such treatment would be continued for as long as needed23. Therefore, regarding the duration of treatment, the simple repetition of a known step to achieve an art-recognized outcome is “merely the logical result of common sense application of the maxim ‘try, try again’” (see, e.g., Perfect Web Technologies, Inc. v. InfoUSA, Inc. 587 F.3d 1324 (Fed. Cir. Dec. 2, 2009)). In the instant case, an artisan would understand that repeating the reference claim method would predictably lead to the successful treatment of HH in a patient in need thereof, and therefore an artisan would readily appreciate that such steps could be repeated to logically achieve the exact outcome identified in the issued claims, namely treatment of a patient in need of HH treatment. Accordingly, the length of treatment duration could be for any desired time period, such as a clinical trial (i.e., weeks), hospital stay (days or weeks), or potentially over a lifetime. Accordingly, claims directed to the length of treatment do not materially or substantially differentiate the claimed invention relative to the teachings of the prior art. Accordingly, the present claims are directed to obvious variants of the reference claims because it is well-within the ordinary skill in the art to practice claimed methods of treating known conditions in known patient populations by administering known compounds within known therapeutically effective ranges to achieve a known outcome, and to simply repeat such treatment for the duration needed (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (C), (D), and (G), 2144.05(I)). Therefore, the instant claims are directed to obvious variants of the issued claims.
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, patentably indistinct variant of the patent 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 88-91, 94, 98-99, 105, 107-108, 110 and 117-119 are rejected.
Response to Arguments
Applicant's arguments filed 3/04/2026 have been fully considered but they are not persuasive. Multiple arguments have been rendered moot in view of the revised rejections necessitated by Applicant’s amendments. Remaining applicable arguments are addressed below. As an initial matter, in view of the maintained or revised rejections using references of record, the Examiner’s prior responses of record remain pertinent and are therefore incorporated into the instant response.
Claim Interpretation
It is the Examiner’s understanding that Applicant disagrees with the Examiner’s prior interpretation of record regarding statements of intended and expected results of positively recited method steps (see, e.g., Reply filed 3/04/2026 at 6 at § “Claim Interpretation” to page 11 at 1st full ¶). These arguments have been fully considered but are substantially rendered moot in view of the newly revised and amended claim scope, which now recites a novel functional limitation.
The functional limitations at issue have not previously been considered on record; but it is the Examiner’s understanding that Applicant is alleging that the newly amended claim preambles reciting
“for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 70 mg/dL as measured by CGM by about 4% to about 26%” at claim 88;
“avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 70 mg/dL as measured by CGM by up to about 26%” at claim 117;
“avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 55 mg/dL as measured by CGM by up to about 24%” at claim 118; and
“avexitide is administered for a time sufficient to reduce diurnal percent time during which the subject’s glucose is less than 40 mg/dL as measured by CGM by up to about 4%” at claim 119
should be given weight, because the limitation at each claim
…sets out specific efficacy benchmarks for the claimed treatment method that constrains how the method is performed and is not merely “a recitation of an intended or expected result”
(see, e.g., Reply filed 3/04/2026 at 9 at 1st full ¶).
Following review of the record, the Examiner’s applicable interpretation of this newly added limitation is set forth above in the Claim Interpretation section of the instant action. As explained therein, the newly added limitations constitute functional limitations that functionally limit the duration of the claimed treatment (i.e., the limitation requires repeating daily, subcutaneous administrations of 60 mg of avexitide to a human subject diagnosed with PBH until the desired “specific efficacy benchmark” is met). Therefore, the functional limitations are understood and herein interpreted as limiting to the extent that the functional limitation requires continued daily treatment until the “specific efficacy benchmarks” are met.
The newly added limitations raise a substantial concern, addressed within the instant Action, because these functionally defined ranges of treatment durations constitute new matter and have been rejected as indefinite as explained above, because no clear minimum duration is identified on record (see, e.g., Rejections under 35 USC §112(a) and §112(b)). For example, a very basic question is left unanswered, namely “How long, in days, should avexitide be administered to such patients to achieve the functionally defined outcome? Two days? Ten Days? 180 days?”. Upon review, the functionally defined durations at instant claims 88 and 117-119, while indefinite and ill-described on record, are reasonably inferred to encompass a treatment duration of “at least 14 days” and timespans of “30 days or less” (see, e.g., instant claim 91).
Applicant’s assertions that the newly added functional limitations at claims 88 and 117-119 are limiting has therefore been fully considered, and such limitations have indeed been considered limiting with respect to the duration of treatment (see Claim Interpretation Section, above). As explained above, for purposes of examination in view of prior art and non-statutory double-patenting rejections, the functionally defined duration of treatment is understood to be satisfied by any prior art treatment wherein humans diagnosed with PBH are subcutaneously administered 60 mg daily of avexitide for at least 14 days or otherwise for “30 days or less”. This is reasonable because if such methods did not yield such “specific efficacy benchmarks” within “30 days or less” upon treating humans diagnosed with PBH by subcutaneously administering 60 mg daily, of avexitide, it would mean that the full scope of the instant claim was not enabled and that the originally filed description was inadequate. For purposes of the instant action, the method is presumed fully enabled to treat a known patient population with a known compound at a known total daily amount via a known administration route for a known treatment duration to achieve a known outcome.
If Applicant means to allege that the prior art, which teaches the administration of the same compound to the same patient population at the same administration route at the same dosage and same dosage frequency, for a presumably the same overlapping treatment duration (e.g., 30 days), is unable to achieve the functional effects claimed, Applicant should so clearly state on record that the instant claim scope is not fully enabled to achieve the recited “specific efficacy benchmarks” using the recited, essential steps set forth at claim 88.
35 USC § 103
It is the Examiner’s understanding that Applicant traverses the prior rejection under 35 USC 103 at pages 6-14 of the Reply (see, e.g., Reply filed 3/04/2026 at 6 at 2nd ¶ to 14 at 3rd full ¶), but Examiner notes that the amendments filed 3/04/2026 have necessitated substantial revisions of the rejections of record, and those revisions have rendered multiple arguments set forth at pages 6-14 of the Reply moot. Remaining applicable arguments are addressed below.
Claim Interpretation: It is the Examiner’s understanding that Applicant disagrees with the Examiner’s prior interpretation of record regarding statements of intended and expected results of positively recited method steps (see, e.g., Reply filed 3/04/2026 at 6 at § “Claim Interpretation” to page 11 at 1st full ¶). These arguments have been substantially rendered moot in view of the revised rejections of record, wherein the novel functional limitations added in the Reply filed 3/04/2026 have been identified as limiting upon the duration of treatment (see discussion above; see also Claim Interpretation section above, incorporated herein).
The prior art teaches methods of administering the same compound to the same patient population via the same administration route, the same dosage, the same dosage frequency, and presumably the same or overlapping treatment duration: As an initial matter, the Examiner’s position is that the claimed invention is prima facie obvious per the rationales of MPEP § 2143(I)(A), (B), (C), (D), (G), and MPEP § 2144.05(I), as explicitly recited in the rejection. As explained in the rejection, it is the Examiner’s position that WO’395 discloses methods of treating HH in HH patients following bariatric surgery by administering the same compound (i.e., avexitide; a.k.a. exendin(9-39)) via the same administration route (subcutaneous) at the same total daily concentration (i.e., 60 mg per day), for the same length of time (i.e., 30 days), in order to predictably HH in such patients, wherein “hypoglycemia is defined as a plasma glucose concentration of ≤55 mg/dL by continuous glucose monitoring (CGM)” (see, e.g., rejection above; see also WO’395 at title, abs, claims, ¶[0157]). Applicant fails to address the rationales supporting a determination of obviousness under MPEP § 2143(I)(A), (B), (C), (D), (G), and MPEP § 2144.05(I)with specificity or otherwise identify any missing element or limitation not taught by the prior art, but required to support a determination of obviousness under such rationales. Accordingly, all aspects not directly disputed and addressed are understood to be undisputed on record.
Allegation that the cited references fail to teach or suggest the present claims: It is the Examiner’s understanding that Applicant is alleging that the prior art of record does not teach or suggest the present claims (see, e.g., Reply filed 3/04/2026 at 11 at 2nd full ¶ to 3rd full ¶), because the prior art does not teach the newly added functional limitations set forth at claims 88 and 117-119 (see id.). This is not persuasive because the newly added, functionally defined, treatment duration is indefinite and constitutes new matter; furthermore, the functional limitations are presumably fully satisfied by performing the active method steps for 14 or more days (e.g., 30 days), which is explicitly taught and disclosed by the prior art, as explained in the revised rejection set forth above. Accordingly, such limitations do not patentably distinguish the pending claims over the prior art because the prior art teaches methods of administering the same compound at the same dosage and dosage frequency to the same patient population for 30 or more days (see, e.g., rejection in view of WO’364, above).
Allegation of no motivation to combine WO’365 and WO’014: It is the Examiner’s understanding that Applicant is alleging that it would not be obvious to combine the prior art disclosures of WO’365 and WO’014 to arrive at the instantly claimed invention (see, e.g., Reply filed 3/04/2026 at 11 at 4th full ¶ to page 14 at 1st full ¶) based upon the assertion that the quoted paragraph of WO’395 is taken out of context, and that such disclosure pertains to BID dosing rather than once daily dosing (see, e.g., Reply filed 3/04/2026 at 12 at 1st line to ¶ beginning with “First”). First, this is not persuasive because it appears to be objectively incorrect since WO’394 and WO’395 overlap substantially in disclosure, and a highly similar disclosure is made in WO’394, which clearly and unambiguously refers to both QD and BID daily administrations, wherein the disclosure regarding “adult patients (60-100 kg)” clearly pertains to QD administration (compare WO’395 at ¶[0104] with WO’394 at ¶¶[0006], [0073]). Second, the Applicant’s argument amounts to an argument of counsel, premised upon assumptions of meaning not supported by objective evidence, which ignore the literal disclosure of the prior art. Third, the issue is moot because in response to the election of species requirement, Applicant made no distinction between 30 mg BID and 60 mg QD, and therefore such species are have consistently been understood to be obvious variants on the instant record (see, e.g., Action mailed 10/11/2024 at 2-3; see also Action mailed 5/22/2025 at 2-4; see also Action mailed 11/05/2025 at 2-4; see also Reply filed 8/01/2024 at 7-9, electing all species of Examples 1-7 rather than a single, disclosed Example as required by the Requirement mailed 2/01/2024 at 3-4; see also MPEP § 809.02(a), noting that Applicant should be required to “elect a single disclosed species”)24. Accordingly, 30 mg BID and 60 mg QD have been consistently understood to be obvious variants of one another on the instant record because it is presumed Applicant properly responded to the species election of record.
Arguments suggesting that prior art disclosures should be ignored are not persuasive: It is the Examiner’s understanding that Applicant is alleging that “WO’014 does not supply the alleged motivation to combine” at least because WO’014 “focuses on exendin-4 derivatives that expressly exclude exendin(9-39)” (see, e.g., Reply filed 3/04/2026 at 12 at ¶ beginning with “Second” to page 14 at 1st ¶). This is objectively incorrect and fully addressed in the rejection of record, and the revised rejection above. It is undisputed that WO’014 primarily focuses upon other exendin derivatives; however, WO’014 explicitly pertains to, discloses, and discusses exendin(9-39), which is utilized as a positive control for other exendin derivatives (see, e.g., WO’014 at ¶¶[0015], [0016], [0060], [0066]-[0067], [0068], [0071]-[0072]). In fact, the disclosure of WO’014 informs artisans that
In some embodiments, a pharmaceutical composition comprising an exendin-4 derivative as disclosed herein is formulated as an injectable suspension in a single-dose pen containing exendin(9-39), a diluent, and one or more needles
(see, e.g., WO’014 at ¶[0060], emphasis added).
Accordingly, WO’014 is analogous art, that literally teaches and discloses exendin(9-39). Although WO’014 pertains primarily to other exendin derivatives, prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including non-exemplified embodiments. Furthermore, Applicant’s allegation regarding what a person of ordinary skill in the art would or would not have been motivated to combine (see, e.g., Reply filed 3/04/2026 at 14 at 1st full ¶), is an argument of counsel unsupported by objective evidence, which is contradicted by the art of record; specifically, WO’364 identifies that circa 2016, an artisan in the GLP-1 antagonist arts would readily appreciate that exendin-4 derivatives, including but not limited to exendin(9-39), could all be utilized to treat HH in post-bariatric surgery patients (see, e.g., WO’364 at claims 1-6; see esp. WO’364 at claims 1-2 and 5-6). Accordingly, an artisan would readily appreciate that teachings pertaining to the treatment of post-bariatric HH patients using one exendin-4 derivative could be applied to another, including exendin(9-39). Accordingly, such arguments are not persuasive because they do not represent the ordinary skill in the exendin-4 derivative arts. Furthermore, MPEP §§ 2123(I)-(II) identify that the mere existence and disclosure of multiple embodiments do not constitute a “teaching away” from a broader disclosure or non-preferred embodiments (see also MPEP §§ 2143(I)).
No evidence of unexpected results or criticality of range has been placed on record: It is the Examiner’s understanding that Applicant is alleging the existence of unexpected results sufficient to rebut prima facie obviousness (see, e.g., Reply filed 3/04/2026 at 10-11 at bridging ¶). To date, zero evidence of unexpected results sufficient to rebut prima facie obviousness and commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 has been placed on record. No evidence showing any criticality of range relative to the closest prior art of record has been placed on record. Rather the instant claims achieve the predicted and expected result taught and suggested by the prior art (i.e., treatment of HH by administering Avexitide), which is pertinent because evidence confirming the expectations of the prior art actually weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)).
Allegations suggesting “skepticism of experts”: It is the Examiner’s understanding that Applicant’s statements amount to a suggestion that the Examiner’s position would be met with skepticism of experts (see, e.g., Reply filed 3/04/2026 at 14 at 1st ¶; see also, Reply filed 9/22/2025 at 9 at 1st ¶). If Applicant means to suggest the existence of skepticism of experts, such evidence should be filed per MPEP § 716.05 as evidence is required to establish skepticism of experts. In the absence of such evidence, such statements are understood to be unsupported conjecture of counsel. 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)), and no objective evidence rebutting this presumption has been placed on record to date.
Recitations of intended and expected results of performing prior art methods does not establish obviousness: It is the Examiner’s understanding that Applicant’s position is that a proper rejections under 35 USC 103 requires verbatim teachings of recitations of intended or expected results (see, e.g., Reply filed 3/04/2026 at 6 at § “Claim Interpretation” to page 11 at 1st full ¶; see also Reply filed 3/06/2025 at 11 at 4th full ¶, 13-14 at bridging ¶, 14-15 at bridging ¶, 15-16 at bridging ¶, 17 at 1st full ¶, 18 at 2nd full ¶, 19-20 at bridging ¶, 20-21 at bridging ¶, 22 at 1st full ¶, 23 at 2nd full ¶). This position is not persuasive or tenable because such intended or expected result would necessarily and inherently be obtained from performing the active method steps at claim 88, unless claim 88 is not fully enabled. Examination has proceeded on the assumption that claim 88 is fully enabled. If Applicant wishes to place evidence on record that such prior art is not enabling, they are welcome to do so and it will be fully considered. However, in view of the instant record, claims merely reciting intended and expected results obtained from performing methods taught or otherwise rendered obvious by the prior art do not weigh in favor of non-obviousness because the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Accordingly, all arguments applicable to the rejection under 35 USC 103 have been fully considered but not found persuasive for the reasons set forth above.
Double Patenting Rejections
It is the Examiner’s understanding that Applicant traverses the non-statutory double patenting rejection at pages 15-21 of the Reply (see, e.g., Reply filed 3/04/2026 at 15 at § “Double Patenting” to 21 at 5th full ¶), and those arguments have been fully considered but not found persuasive as explained below. Examiner notes that Applicant appears to repeat multiple arguments and rationales, and therefore has opted to address common rationales a single time as set forth below. As an initial matter, it is noted that the rejections have revised as necessitated by the Applicant’s amendments, and therefore some arguments have been rendered moot. Remaining applicable arguments are addressed below.
Allegation that the cited references fails to teach or suggest the newly added functional limitation pertaining to treatment duration as recited at claims 88 and 117-119: It is the Examiner’s understanding that Applicant is alleging that the issued patents (or co-pending applications) do not claim an obvious variant of the instant claim scope because the issued (or co-pending) claims do not recite the functional limitations set forth at amended claims 88 and 117-119 (see, e.g., Reply filed 3/04/2026 at 14-15 at bridging ¶, 15 at 1st full ¶, 15 at final three ¶¶, 16 at 4th and 5th full ¶¶, 17 at 1st and 2nd full ¶¶, 17-18 at bridging ¶, 18 at 1st and 2nd full ¶¶, 19 at final three ¶¶, 19 at 4th to 5th full ¶¶, 20 at 3rd to 4th full ¶¶, 21 at 1st to 2nd full ¶¶, 22 at final ¶). This has been fully considered and the newly added amendments have been explicitly addressed and considered in view of the cited references. As explained in the revised rejections of record, the pending claims continue to read upon obvious variants of the issued and copending claims because the newly added functional limitations are understood to functionally define a treatment duration, but the references of record are understood to encompass treatment variations of 30 days or more, which is understood to satisfy the functionally defined treatment duration now claimed. Accordingly, such amendment has been fully considered but not found persuasive for reasons of record.
Request for rejection to be held in abeyance is acknowledged: Examiner acknowledges Applicant’s request that the provisional rejection in view of copending Application No. 18/745,091 be held in abeyance (see, e.g., Reply filed 3/04/2026 at 21 at final ¶). The rejection is maintained as revised above, and all revisions were necessitated by Applicant’s amendments.
Conclusion
Accordingly, all applicable arguments have been fully considered but not found persuasive in view of the revised rejections as set forth above. All revisions were necessitated by Applicant’s amendments.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Kerfurt et al.25 establishes that the “Mixed Meal-Test” is a prior art element used to “assess hypoglycemia” and for “detection of clinically relevant hypoglycemia”, which is equivalent to other prior art tests for “assess[ing] hypoglycemia”, such as an “Oral Glucose Tolerance Test”, “finger-stick glucometer”, or “continuous glucose monitoring” (see, e.g., Kefurt at abs, 565 at col I at 1st full ¶, 565 at col II at 1st full ¶). Kefurt also identifies that multiple methods of detecting clinically relevant hypoglycemia may be utilized in a single study (see, e.g., Kefurt at 565 at col I at § Methods), which may help provide higher quality data pertinent to detecting clinically relevant hypoglycemia.
Sah26 discusses the Billroth I and II surgeries (see, e.g., Sah at title, abs).
Conclusion
No claims are allowed.
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/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 DLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS
2 compare WO’395 at ¶[0044] with Spec. filed 4/14/2021 at ¶[0030].
3 compare WO’395 at ¶[0044] with Spec. filed 4/14/2021 at ¶[0030].
4 See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
5 See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
6 See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
7 Per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’937 at col. 24 to 25 at bridging ¶), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id).
8 See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
9 Per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’992 at col. 24 at lines 37-50), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id).
10 See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
11 Per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’991 at col. 18 at lines 51-65), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id).
12 See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
13 Per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’782 at cols. 18-19 at bridging ¶), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id).
14 See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
15 Per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’995 at col. 24 at line 60 to col. 25 at line 9), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id).
16 See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
17 Per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’663 at col. 19 at lines 5 to line 18), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id).
18 See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
19 Per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’484 at col. 18 at lines 50-60), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id).
20 See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
21 Per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., US’086 at col. 18 at lines 50-60), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id).
22 See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
23 Per MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”. Here, obvious variations of the duration of treatment methods as claimed are explicitly discussed (see, e.g., App’091 at Spec. filed 6/17/2024 at ¶[0105]), which explains that the duration of treatment may range from “weekly” to “30 days”, “months”, and “at least one year” to even “for the rest of the patient’s lifetime” (see id).
24 Examination has proceeded on the basis that the Applicant properly elected a narrow subgenus of patentably indistinct species, wherein all such species within the Examples are not patently distinct (i.e., obvious variants) (See 37 CFR 1.56(b)(1)-(3); see also Teva Pharmaceuticals USA, Inc. v. Sandoz, Inc., 789 F. 3d 1335 (2015), at 1343, stating “We have said before, and reaffirm today, that past and future prosecution of related patents may be relevant to the construction of a given claim term”. See, also, Springs Window Fashions LP v. Novo Indus., L.P., 323 F.3d 989, 995 (Fed.Cir.2003), noting that “The public notice function of a patent and its prosecution history requires that a patentee be held to what he declares during the prosecution of his patent”.
25 Kefurt R, Langer FB, Schindler K, Shakeri-Leidenmühler S, Ludvik B, Prager G. Hypoglycemia after Roux-En-Y gastric bypass: detection rates of continuous glucose monitoring (CGM) versus mixed meal test. Surg Obes Relat Dis. 2015 May-Jun;11(3):564-9. doi: 10.1016/j.soard.2014.11.003. Epub 2014 Nov 13. PMID: 25737101; hereafter “Kefurt”; cited in previous action.
26 Sah BK, Chen MM, Yan M, Zhu ZG. Gastric cancer surgery: Billroth I or Billroth II for distal gastrectomy? BMC Cancer. 2009 Dec 9;9:428. doi: 10.1186/1471-2407-9-428. PMID: 20003202; PMCID: PMC2794879; hereafter “Sah”; cited in previous action.
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