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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2/12/2026 has been entered.
Claim Status
Claims 1, 5, 7, 9, 19, 29-30, and 72-73 are pending. Claim 11 was canceled and claim 1 was amended in the Reply submitted 2/12/2026. Claim 72 remains withdrawn. Claims 1, 5, 7, 9, 19, 29-30, and 73 are presently considered.
Election/Restrictions
Applicant’s election without traverse of Group I (Claims 1, 5, 7-11, 19, and 29-31) and the subgenus of patentably indistinct species of Example 5 (Spec. at 33 line 9 to page 34 at line 14), namely a composition containing 20 mg/mL ZP1848-acetate (SEQ ID NO: 1, wherein R1 is H, Z1 is absent, X5 is Thr, X11 is Ala, Z2 is (K)6, and R2 is NH2,), 15 mM histidine buffer, 230 mM mannitol, and having a pH of 7.0 in the reply filed on 10/26/2023 was previously acknowledged. Critically, formulations #1-10 at Example 5 differed only with respect to Acetate (ranging from 20.3 mM to 50.8 mM), and a specific value was not elected; therefore, the patentably indistinct subgenus was understood to have a variable amount of acetate.
Following extensive search and examination, the originally elected subgenus of patentably indistinct species was previously deemed anticipated and/or obvious in view of the prior art as applied in the Action mailed 11/13/2023.
In the Reply filed 3/08/2024, Applicant amended the claims to include product-by-process language (“formed by combining”), and to alter then GLP-2 analogue to specifically require ZP1848-acetate having the form:
HGEGTFSSELATILDALAARDFIAWLIATKITDKKKKKK-NH2 - x(CH3COOH)
wherein “x” is 1.0 to 8.0. Examiner previously noted that Applicant failed to identify that the originally elected species continued reading upon the amended claims as required (see, e.g., Requirement mailed 08/29/2023 at 11-12 at bridging ¶; see Action mailed 4/15/2024 at 2-3). Examiner proceeded with Examination of embodiments having 20 mg/mL ZP1848-acetate (SEQ ID NO: 1), 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and having a pH of 7.0.
In the Reply filed 1/15/2025, Applicant alleged that the originally elected species had an x of 4.4, corresponding to 6% acetate (see, e.g., Reply filed 1/15/2025 at 4 at § Elected Species). Examiner explained that this was not persuasive in view of Table 4 within Example 5 at pages 33-34 of the originally filed specification as filed 3/15/2021, because Formulation #1-10 varies in “Acetate %” from 6 to 15 (see Spec. filed 3/15/2021 at Example 5 at Table 4 at 34), and the originally elected subgenus of species identified in the Reply filed 10/26/2023 corresponded to the Applicant’s statement “Applicant elects Example 5” (see Reply filed 10/26/2023).
It was the Examiner’s understanding that Applicant was attempting to patentably distinguish species within the narrow subgenus of patentably indistinct species of Example 5 originally elected based on acetate content.
As amended in the Reply filed 1/15/2025, it is the Examiner’s understanding that the amended claims continue to read upon the subgenus of species consisting of 20 mg/mL ZP1848-acetate (SEQ ID NO: 1), 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and having a pH of 7.0. These formulations are understood to fully satisfy all functional limitations recited at amended claim claim 1 (see, e.g., instant claim 1(i)-((iv)).
Per MPEP § 803.02(III)(A), claims 1, 5, 7, 9, 11, 19, and 29-30 are rejected in view of a subgenus of the originally elected species and claims that do not read upon the originally elected species are withdrawn.
Claim 72 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention for reasons set forth previously on record, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/26/2023.
Claims 1, 5, 7, 9, 19, 29-30 and 73 are presently considered.
Priority
The priority claim to EP18197755.4 (filed 9/28/2018) is acknowledged. However, Examiner notes that the priority document material differs from the instant Specification; for example, EP’755.4 lacks all disclosures pertaining to at least at instant Examples 6-11 (compare instant Spec. at Examples 6-11 with EP18197755.4, noting that EP’755.4 lacks such disclosures). According, priority may be denied upon amendments attempting to incorporate the data set forth at such Examples.
Information Disclosure Statement
The IDS filed 2/12/2026 is 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 (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
The interpretations of record set forth in the Action mailed 4/15/2025 at pages 8-9 are incorporated into the instant action.
Amended claim 1 is representative of the pending claim scope, and is directed to a product, namely a “formulation comprising a [GLP-2] analogue solution”. The applicable claim interpretation is discussed below.
The added phrase at claim 1(iv), reciting “wherein . . . and (iv) the formulation is stable for at least 18 months when stored at 2-8 °C” does not correspond to a structure/function relationship commensurate in scope with the pending claim scope. Accordingly, the “wherein” clause is understood to be a recitation of a intended or expected result that is deemed fully satisfied by any prior art that satisfies the structural limitations set forth in the body of the claim (see also MPEP § 2111.04(I), noting that “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”). Accordingly, the phrase is deemed fully satisfied by any formulation comprising about 5-25 mg/mL ZP1848-acetate (SEQ ID NO: 1), about 15 mM histidine buffer, about 230-260 mM of mannitol, about 20.3 to 37.3 mM acetate, and arginine such that the formulation has a pH of about 7.0.
The term “about” is undefined on record. The term “about” is given its ordinary meaning in view of the biochemical arts, and is understood to mean “within 20 percent” (see, e.g., US 2009/0028832 A1 at ¶[0111]; see also US 2009/0105341 A1 at ¶[0049]; see also US 2012/0178676, at ¶[0277]). Accordingly, with respect to the instant disclosure and with prior art of record, unless the term “about” is otherwise clearly defined, the term is reasonably inferred to indicate a range either “within 20 percent” of a recited number. Therefore, the range of “about 5 mM to about 25 mM” is reasonably inferred to include at least a range of 4 mM to 30 mM; the range of “about 7.0” is reasonable inferred to include at least a range of 5.6 to 8.4; etc., etc.
The structure of ZP1848 (present in originally elected species) is understood to be the sequence of
HGEGTFSSELATILDALAARDFIAWLIATKITDKKKKKK-NH2
This is a prior art structure, first taught and disclosed in WO2006/117565A1 (Nov. 9, 2006; Larsen et al.) as “1848” or [Gly2, Glu3, Thr5, Ser8, Leu10, Ala 11, 16, 24, 28]hGLP-2(1-33)-(Lys)6-NH2 (see, e.g., WO’565 at 20 at lines 39-40, 22 at lines 4-12, 42 at “1848”, claim 11, 14, passim). Accordingly, the structure is prior art element. ZP1848-acetate is understood to be the acetate salt of ZP1848 and is reasonably understood to necessarily form in the presence of acetic acid.
Claim 1 recites and requires product-by-process language (see, e.g., claim 1 at line 2, reciting “solution formed by combining”. Per the MPEP, “even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself” (see, e.g., MPEP § 2113). Here, the product-by-process language of amended claim 1 is reasonably inferred to read upon at least a subgenus of the originally elected species, namely formulations of 20 mg/mL ZP1848-acetate (SEQ ID NO: 1), 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and having a pH of 7.0. This is pertinent because although amended claim 1 recites the component of
(x) solid ZP1848-acetate, consisting of
[H-HGEGTFSSELATILDALAARDFIAWLIATKITDKKKKKK-NH2 (SEQ ID NO: 1)] -x(CH3COOH)
wherein “x” is 1.0 to 8.0;
this component is not actually required to be present in the final claimed composition, but is only present in the product-by-process recitation wherein the final, claimed product is “formed by combining” it with an aqueous buffer and a tonicity modifier. Accordingly, ZP1848-acetate and “x” recitation are reasonably inferred to be the equivalent of combining ZP1848 and approximately 20.3 to 37.3 mM acetate with “an aqueous buffer” and “a tonicity modifier” (see, e.g., instant claim 1 at (x), (y), (z).
At claim 5, the “wherein” is reasonably understood to be a recitation of intended or expected results fully satisfied by all embodiments within the scope of instant claim 1 that satisfy the positively recited structural limitations at claim 1(a)-(d) (see, e.g., MPEP § 2111.04(I), noting that “Claim scope is not limited by . . . .claim language that does not limit a claim to a particular structure”).
Amended claims 29-30 recite the range of 2.0 to 7.0 molar equivalents and 3.0 to 6.0 molar equivalents. These limitations refer to product-by-process language at claim 1(x), 1(y), and 1(z) (see, e.g., claim 1 at line 2, reciting “formed by combining” and “to produce the formulation wherein”). Accordingly, the final product, as claimed, is not required to comprise the recited product of claim 1(x). Furthermore, claim 1 recites open-ended “comprising” language, and therefore additional acetate may be present or added, so long as the proviso of claim 1(i) is satisfied. Therefore, for purposes of applying prior art, the ranges are deemed fully satisfied by at least combinations of ZP1848 and approximately 20.3 to 37.3 mM acetate with “an aqueous buffer” and “a tonicity modifier” (see, e.g., instant claim 1 at (x), (y), (z)). If this is incorrect, Applicant should so clearly state, and such claims will be withdrawn as not reading upon the originally elected species.
Additional claim interpretations are set forth below.
Maintained Rejections as Necessitated by Applicant Amendment
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.
[Maintained Rejection 01]
Claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected under 35 U.S.C. 103 as being unpatentable over WO2006/117565A1 (Nov. 9, 2006; Larsen et al.; cited in previous action).
Claim Interpretation: The applicable claim interpretation has been set forth above in a separate section entitled “Claim Interpretations” above, and/or discussed in preceding rejections. Those interpretations and discussions are incorporated herein unless otherwise explicitly stated. As noted above, the product-by-process language of amended claim 1 is presumed to be fully satisfied by all embodiments comprising the equivalent of 20 mg/mL ZP1848-acetate (SEQ ID NO: 1), 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and having a pH of 7.0. Additional claim interpretations are discussed below.
Regarding instant claims 1, 5, 7, 9, 19, 29-30, and 73, WO’565 pertains to GLP-2 analogues, methods of use, and compositions thereof (see, e.g., WO’565 at title, abs, claims, page 32 at line 15 to page 33 at line 6). Regarding the preamble of claim 1 and a “stable” pharmaceutical composition, the applicable interpretation of the preamble has been set forth in the Claim Interpretation section above, which is incorporated herein. In addition, WO’565 explicitly teaches that the pharmaceutical formulations “may be formulated as pharmaceutical compositions prepared for storage” (see, e.g., WO’565 at 28 at lines 15-20) and identifies that the disclosed GLP-2 analogues are “stable” (see, e.g., WO’565 at 2 at lines 26-30), and therefore an artisan would reasonably conclude such formulations were necessarily “stable” and suitable for “storage” as explicitly taught and suggested by WO’565. Regarding instant claim 1(x) and the structure of the GLP-2 analogue of ZP1848, WO’564 teaches and discloses at least compound 1848, which has the following structure:
HGEGTFSSELATILDALAARDFIAWLIATKITDKKKKKK-NH2,
and is identified as [Gly2, Glu3, Thr5, Ser8, Leu10, Ala 11, 16, 24, 28]hGLP-2(1-33)-(Lys)6-NH2 (see, e.g., WO’565 at 20 at lines 39-40, 22 at lines 4-12, 42 at “1848”, claim 11, 14, passim). This structure satisfies the requirements of instant claim 1 wherein R1 is H, Z1 is absent, X5 is Thr, X11 is Ala, Z2 is (K)6, and R2 is NH2 (compare id. with instant claim 1). Regarding instant claim 1(a), 5, 7, 9, 19, 29-30, 73, and the concentration of the GLP-2 analogue, WO’565 explicitly teaches and directs artisans to GLP-2 analogue formulations comprising “most preferably from 10 to 30 mg/mL” of a therapeutic GLP-2 analogue (see, e.g., WO’565 at 32 at line 15 to page 33 at line 6). Therefore, the prior art directs artisans to utilize the same or overlapping concentration of GLP-2 analogues (see, e.g., 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 1(b), 5, 10-11, 19, and the use of a histidine buffer at a concentration of about 15 mM, WO’565 explicitly teaches and directs artisans to GLP-2 analogue formulations comprising “most preferably from 5 to 50 mM L-histidine” (see, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see esp. id. at 32 at line 34; see, e.g., 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 1(c), 5, 19, and mannitol at a concentration of about 230 mM, WO’565 explicitly teaches and directs artisans to GLP-2 analogue formulations comprising “most preferably from 100 mM to 230 mM” of mannitol (see, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see, e.g., 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 1(d), 5, 19, “arginine q.s. to provide a formulation having a pH of about of “about 7.0”, WO’565 explicitly teaches and directs artisans to GLP-2 analogue formulations comprising “L-Arginine . . . up to 200 mM”, wherein the pH is identified as “most preferably from 6.7 to 7.3” (see, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see, e.g., 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 1(i) and the “total acetate concentration . . . less than or equal to 8 molar equivalents of acetate per molar equivalent of the GLP-2 analogue”, the amended limitation is understood to be necessarily satisfied by prior art that discloses formulations of GLP-2 analogues comprising approximately 20.3 to 37.3 mM of acetic acid or less, which is reasonable in view of the instant disclosure (see, e.g., Spec. filed 3/16/2021 at Table 4 on 34). This is pertinent because WO’565 explicitly teaches and directs artisans to GLP-2 analogue formulations comprising “acetic acid” “most preferably from 0.5 to 50 mM into solution” (see, e.g., WO’565 at 32 at line 15 to page 33 at line 6), and WO’565 explicitly teaches the usage of acetate salts (see, e.g., WO’565 at 17 at lines 9-19, 30 at lines 7-12). Accordingly, in view of the disclosure directing an artisan to use acetic acid “most preferably from 0.5 to 50 mM into solution” (see, e.g., WO’565 at 32 at lines 15 to 30), it is reasonably understood that the prior art formulation renders the limitation of claim 1(i) obvious because “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists” (see, e.g., MPEP § 2144.05(I)). Regarding instant claim 1(y) and an aqueous buffer, WO’565 explicitly teaches and directs artisans to aqueous GLP-2 analogue formulations as evidenced by the explicit reference to pH values and “L-histidine dissolved in water” (see, e.g., WO’565 at 32 at line 15 to page 33 at line 6). Regarding instant claim 1(i)-(iii), these recitations do not appear to functional limitations corresponding to particular structures or structural limitations. As noted in the claim interpretation section above, claims 1(i)-(iii) have been interpreted in view of MPEP § 2111.04(I). Therefore, the “wherein” clauses at claim 1(i)-(iii) are understood to merely recite intended or expected results fully satisfied by all embodiments satisfying the positively recited structural limitations set forth in the body of the claim 1 at claim 1(x) and (a)-(d). This interpretation is consistent with the interpretation of record identified in the Requirement (see, e.g., Requirement mailed 8/29/2023 at 3) which was not disputed by the Applicant (see, e.g., Reply filed 10/26/2023, passim). Furthermore, this interpretation is consistent with the formulation “consisting of” the components recited at previously pending claim 31, now canceled (i.e., ZP1848-acetate, histidine buffer, mannitol, arginine q.s. to provide a pH of about 7.0, wherein ZP1848 acetate is understood to arise from ZP1848 and acetic acid). Accordingly, the limitations of instant claim 1(i)-(iii) are deemed fully satisfied by the embodiments and compositions taught by the prior art, which comprise the same components at overlapping concentration ranges (see, e.g., WO’565 at 32 at line 15 to page 33 at line 6).
The disclosure of WO’565 differs from the instant claim scope as follows: Although WO’565 discloses the same GLP-2 analogue of ZP1848 (see, e.g., WO’565 at 20 at lines 39-40, 22 at lines 4-12, 42 at “1848”) and formulations comprising the same components at overlapping concentrations (see, e.g., WO’565 at 32 at line 15 to page 33 at line 6), WO’565 does not actually reduce to practice a composition comprising “about 5 mg/mL to about 25 mg/mL” of a GLP-2 analogue such as ZP1848-acetate, “about 15 mM ” of histidine buffer, “about 230-to about 260 mM” of mannitol, and “arginine q.s. to provide a formulation having a pH of about 7.0” as presently claimed.
However, WO’565 explicitly teaches and directs artisans to utilize the exact GLP-2 analogue of “1848” (see, e.g., WO’565 at 20 at lines 39-40, 22 at lines 4-12, 42 at “1848”), discloses that the GLP-2 analogue may comprise acetate (see, e.g., WO’565 at 17 at lines 9-19, 30 at lines 7-12), to form “stable” formulations suitable for “storage” (see, e.g., WO’565 at 2 at lines 26-30, 28 at lines 15-20), and explicitly directs artisans to utilize formulations comprising 10-30 mg/mL of GLP-2 analogue, 5 to 50 mM L-histidine, Mannitol at 100 mM to 230 mM, arginine up to 200 mM with a pH of 6.7 to 7.3, and acetic acid “most preferably” from 0.5 to 50 mM in an aqueous solution (see, e.g., WO’565 at 32 at line 15 to page 33 at line 6). Accordingly, the prior art explicitly directs artisans to utilize pharmaceutical formulations as presently claimed, comprising the exact same components at the exact same or otherwise overlapping concentrations (see, e.g., 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): The invention is obvious because it is the combination of prior art elements taught by WO’565 (i.e., known GLP-2 analogues, histidine buffer, mannitol, arginine for pH of 6.7 to 7.3, and acetic acid to obtain acetate salts) according to known methods of making GLP-2 analogue containing pharmaceutical compositions as taught by WO’565, to yield predictable results, namely pharmaceutical compositions comprising 10-30 mg/mL of GLP-2 analogue “1848”, 5 to 50 mM L-histidine, Mannitol at 100 mM to 230 mM, arginine up to 200 mM with a pH of 6.7 to 7.3, and acetic acid at 0.5 to 50 mM in an aqueous solution, wherein such formulations are useful for storage and methods as taught and disclosed by WO’565 (see, e.g., MPEP § 2143(I)(A), (G); 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”). Furthermore, each component merely performs the same 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 in the art to make a pharmaceutical formulation comprising prior art components at known concentration ranges to obtain products exactly as taught and disclosed by the prior art.
Accordingly, claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected.
[Maintained Rejection 02]
Claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 7,563,770 B2 (Jul. 21, 2009; cited in previous action).
Claim Interpretation: The applicable claim interpretation has been set forth above in a separate section entitled “Claim Interpretations” above, and/or discussed in preceding rejections. Those interpretations and discussions are incorporated herein unless otherwise explicitly stated. As noted above, the product-by-process language of amended claim 1 is presumed to be fully satisfied by all embodiments comprising the equivalent of 20 mg/mL ZP1848-acetate (SEQ ID NO: 1), 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and having a pH of 7.0. Additional claim interpretations are discussed below.
US’770 is understood to overlap in scope with the instant claims as explained below (see, e.g., US’770 at claims 1-2, passim). Regarding the specific GLP-2 analog of “ZP1848” now required by amended claims 1, 5, 7, 9, 19, 29-30, and 73, US’770 teaches and discloses instant ZP1848 (compare US’770 at col. 18. at lines 10-20 at SEQ ID NO: 36 identified as “1848” with instant claim 1 and instant SEQ ID NO: 1, showing 100% identity).
The disclosure of the prior art reference differs from the instant claim scope as follows: Although the prior art reference discloses pharmaceutical formulations comprising a GLP-2 analog, it differs from the instant claims because it does not explicitly reduce to practice a formulation of the GLP-2 analog of “1848” that comprises 20 mg/mL “1848”, 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, has a pH of 7.0, and contains arginine in an amount sufficient “to provide a formulation having a pH of about 6.6 to about 7.4” as presently claimed.
However, the prior art reference explicitly teaches, discloses, and directs artisans to utilize explicitly disclosed “pharmaceutical” compositions (see, e.g., US’770 at col 29 at lines 3-23). Specifically, US’770 expressly identifies and directs artisans to make and utilize pharmaceutical formulations comprising “most preferably” 10-30 mg/mL of GLP-2 analogue, “most preferably” 5 to 50 mM L-histidine, “most preferably” mannitol at 100 mM to 230 mM (and “preferably” 30 to 300 mM), arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at “most preferably” 0.5 to 50 mM in an aqueous solution, wherein the acetic acid would be reasonably inferred to be the equivalent of an acetate salt of the GLP-2 analogue in the product-by-process language of instant claim 1 (see, e.g., US’770 at col 29 at lines 3-23).
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): The invention is obvious because it is the combination of the exact prior art elements taught by US’770 (i.e., known GLP-2 analogues, histidine buffer, mannitol, arginine for pH of 6.7 to 7.3, and acetic acid to obtain acetate salts) according to known methods of making GLP-2 analogue containing pharmaceutical compositions as claimed by US’770, to yield predictable results, namely pharmaceutical compositions comprising 10-30 mg/mL of GLP-2 analogue “1848”, 5 to 50 mM L-histidine, Mannitol at 100 mM to 230 mM, arginine up to 200 mM with a pH of 6.7 to 7.3, and acetic acid at 0.5 to 50 mM in an aqueous solution (see, e.g., MPEP § 2143(I)(A), (G); 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”). Furthermore, each component merely performs the same 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 in the art to make a pharmaceutical formulation comprising prior art components at known concentration ranges to obtain products exactly as taught and disclosed by the prior art.
Accordingly, claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected.
[Maintained Rejection 03]
Claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 7,745,403 B2 (Jun. 29, 2010; cited in previous action).
Claim Interpretation: The applicable claim interpretation has been set forth above in a separate section entitled “Claim Interpretations” above, and/or discussed in preceding rejections. Those interpretations and discussions are incorporated herein unless otherwise explicitly stated. As noted above, the product-by-process language of amended claim 1 is presumed to be fully satisfied by all embodiments comprising the equivalents of 20 mg/mL ZP1848-acetate (SEQ ID NO: 1), 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and having a pH of 7.0. Additional claim interpretations are discussed below.
The primary reference overlaps in scope with the instant claims as explained below (see, e.g., US’403 at claims 1-2, passim). Regarding the GLP-2 analog structure of ZP1848 as recited at instant claims 1, 5, 7, 9, 19, 29-30, and 73, the primary reference teaches and discloses the GLP-2 analog structure of instant ZP1848 (compare US’403 at col. 18. at lines 50-56 at SEQ ID NO: 36 identified as “1848” with instant claim 1 and instant SEQ ID NO: 1, showing 100% identity).
The disclosure of the primary reference differs from the instant claims as follows: Although the prior art reference directs artisans to make and use pharmaceutical formulations comprising a GLP-2 analog like “1848”, it differs from the instant claims because it does not explicitly reduce to practice a formulation of the GLP-2 analog of “1848” that comprises 20 mg/mL “1848”, 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, has a pH of 7.0, and contains arginine in an amount sufficient “to provide a formulation having a pH of about 6.6 to about 7.4” as presently claimed.
However, the prior art reference explicitly teaches, discloses, and directs artisans to utilize explicitly disclosed “pharmaceutical” compositions (see, e.g., US’403 at col 29 at lines 10-32; see also id. at col. 28 at lines 39-58). Specifically, US’403 expressly identifies and directs artisans to make and utilize pharmaceutical formulations comprising “most preferably” 10-30 mg/mL of GLP-2 analogue, “most preferably” 5 to 50 mM L-histidine, “most preferably” mannitol at 100 mM to 230 mM (and “preferably” 30 to 300 mM), arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at “most preferably” 0.5 to 50 mM in an aqueous solution, wherein the acetic acid would be reasonably inferred to be the equivalent of an acetate salt of the GLP-2 analogue in the product-by-process language of instant claim 1 (see, e.g., US’403 at col 29 at lines 10-32; see also id. at col. 28 at lines 39-58).
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): The invention is obvious because it is the combination of the exact prior art elements taught by US’403 (i.e., known GLP-2 analogues, histidine buffer, mannitol, arginine for pH of 6.7 to 7.3, and acetic acid to obtain acetate salts) according to known methods of making and using GLP-2 analogue containing pharmaceutical compositions in methods as claimed by US’403, to yield predictable results, namely pharmaceutical compositions comprising 10-30 mg/mL of GLP-2 analogue “1848”, 5 to 50 mM L-histidine, Mannitol at 100 mM to 230 mM, arginine up to 200 mM with a pH of 6.7 to 7.3, and acetic acid at 0.5 to 50 mM in an aqueous solution (see, e.g., MPEP § 2143(I)(A), (G); 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”). Furthermore, each component merely performs the same 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 in the art to make a pharmaceutical formulation comprising prior art components at known concentration ranges to obtain products exactly as taught and disclosed by the prior art.
Accordingly, claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected.
[Maintained Rejection 04]
Claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 8,163,696 B2 (Apr. 24, 2012; cited in previous action).
Claim Interpretation: The applicable claim interpretation has been set forth above in a separate section entitled “Claim Interpretations” above, and/or discussed in preceding rejections. Those interpretations and discussions are incorporated herein unless otherwise explicitly stated. As noted above, the product-by-process language of amended claim 1 is presumed to be fully satisfied by all embodiments comprising the equivalents of 20 mg/mL ZP1848-acetate (SEQ ID NO: 1), 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and having a pH of 7.0. Additional claim interpretations are discussed below.
The primary reference overlaps in scope with the instant claims as explained below (see, e.g., US’696 at claims 1-4, passim). Regarding the GLP-2 analog structure of ZP1848 as recited at instant claims 1, 5, 7, 9, 19, 29-30, and 73, the primary reference claims methods necessitating the existence of pharmaceutical compositions comprising salts of SEQ ID NO: 36 (compare US’696 at claims 1-4, SEQ ID NO: 36 with instant claim 1 and ZP1848 of instant SEQ ID NO: 1, showing 100% identity). Notably, the sequence recited in the claims of US’696 is ZP1848 (compare US’696 at col. 19. at lines 35-45 at SEQ ID NO: 36 identified as “1848” and claims 1-4 with instant claim 1 and instant SEQ ID NO: 1, showing 100% identity).
The disclosure of the primary reference differs from the instant claims as follows: Although the prior art reference directs artisans to make and use pharmaceutical formulations comprising a GLP-2 analog like “1848”, it differs from the instant claims because it does not explicitly reduce to practice a formulation of the GLP-2 analog of “1848” that comprises 20 mg/mL “1848”, 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, has a pH of 7.0, and contains arginine in an amount sufficient “to provide a formulation having a pH of about 6.6 to about 7.4” as presently claimed.
However, the prior art reference explicitly teaches, discloses, and directs artisans to utilize pharmaceutically acceptable compositions of the recited GLP-2 analog “1848” (SEQ ID NO: 36) suitable for use in the recited methods (see, e.g., US’696 at claims 1-4); and specifically directs artisans to make and use pharmaceutical formulations comprising “most preferably” 10-30 mg/mL of GLP-2 analogue, “most preferably” 5 to 50 mM L-histidine, “most preferably” mannitol at 100 mM to 230 mM (and “preferably” 30 to 300 mM), arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at “most preferably” 0.5 to 50 mM in an aqueous solution, wherein the acetic acid would be reasonably inferred to be the equivalent of an acetate salt of the GLP-2 analogue in the product-by-process language of instant claim 1 (see, e.g., US’696 at col 29 at lines 35-60; see also id. at col. 30 at lines 10-30).
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): The invention is obvious because it is the combination of the exact prior art elements (i.e., known GLP-2 analogues, histidine buffer, mannitol, arginine for pH of 6.7 to 7.3, and acetic acid to obtain acetate salts) according to known methods of making and using GLP-2 analogue containing pharmaceutical compositions as recited in methods claimed by the US’696, to yield predictable results, namely pharmaceutical compositions for use in such methods comprising 10-30 mg/mL of GLP-2 analogue “1848”, 5 to 50 mM L-histidine, Mannitol at 100 mM to 230 mM, arginine up to 200 mM with a pH of 6.7 to 7.3, and acetic acid at 0.5 to 50 mM in an aqueous solution (see, e.g., MPEP § 2143(I)(A), (G); 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”). Furthermore, each component merely performs the same 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 in the art to make a pharmaceutical formulation comprising prior art components at known concentration ranges to obtain products exactly as taught and disclosed by the prior art.
Accordingly, claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected.
[Maintained Rejection 05]
Claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 8,263,552 B2 (Sept. 11, 2012; cited in previous action).
Claim Interpretation: The applicable claim interpretation has been set forth above in a separate section entitled “Claim Interpretations” above, and/or discussed in preceding rejections. Those interpretations and discussions are incorporated herein unless otherwise explicitly stated. As noted above, the product-by-process language of amended claim 1 is presumed to be fully satisfied by all embodiments comprising the equivalents of 20 mg/mL ZP1848-acetate (SEQ ID NO: 1), 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and having a pH of 7.0. Additional claim interpretations are discussed below.
The primary reference overlaps in scope with the instant claims as explained below (see, e.g., US’552 at claims 1-8, passim). Regarding the GLP-2 analog structure of ZP1848 as recited at instant claims 1, 5, 7, 9, 19, 29-30, and 73, the primary reference claims pharmaceutical compositions comprising salts of SEQ ID NO: 36 (compare US’552 at claims 1-8, SEQ ID NO: 36 with instant claim 1 and ZP1848 of instant SEQ ID NO: 1, showing 100% identity). Notably, the sequence recited in the claims of US’553 is ZP1848 (compare US’553 at col. 19. at lines 35-45 at SEQ ID NO: 36 identified as “1848” and claims 1-8 with instant claim 1 and instant SEQ ID NO: 1, showing 100% identity).
The disclosure of the primary reference differs from the instant claims as follows: Although the prior art reference directs artisans to make and use pharmaceutical formulations comprising a GLP-2 analog like “1848”, it differs from the instant claims because it does not explicitly reduce to practice a formulation of the GLP-2 analog of “1848” that comprises 20 mg/mL “1848”, 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, has a pH of 7.0, and contains arginine in an amount sufficient “to provide a formulation having a pH of about 6.6 to about 7.4” as presently claimed.
However, the prior art reference explicitly teaches, discloses, and directs artisans to utilize pharmaceutically acceptable compositions of the recited GLP-2 analog “1848” (SEQ ID NO: 36) (see, e.g., US’553 at claims 1-8); and specifically directs artisans to make and use pharmaceutical formulations comprising “most preferably” 10-30 mg/mL of GLP-2 analogue, “most preferably” 5 to 50 mM L-histidine, “most preferably” mannitol at 100 mM to 230 mM (and “preferably” 30 to 300 mM), arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at “most preferably” 0.5 to 50 mM in an aqueous solution, wherein the acetic acid would be reasonably inferred to be the equivalent of an acetate salt of the GLP-2 analogue in the product-by-process language of instant claim 1 (see, e.g., US’552 at col 29 at lines 35-55; see also id. at col. 30 at lines 5-30).
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): The invention is obvious because it is the combination of the exact prior art elements taught by the primary reference (i.e., known GLP-2 analogues, histidine buffer, mannitol, arginine for pH of 6.7 to 7.3, and acetic acid to obtain acetate salts) according to known methods of making GLP-2 analogue containing pharmaceutical compositions as claimed by US’552, to yield predictable results, namely pharmaceutical compositions comprising 10-30 mg/mL of GLP-2 analogue “1848”, 5 to 50 mM L-histidine, Mannitol at 100 mM to 230 mM, arginine up to 200 mM with a pH of 6.7 to 7.3, and acetic acid at 0.5 to 50 mM in an aqueous solution (see, e.g., MPEP § 2143(I)(A), (G); 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”). Furthermore, each component merely performs the same 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 in the art to make a pharmaceutical formulation comprising prior art components at known concentration ranges to obtain products exactly as taught and disclosed by the prior art.
Accordingly, claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected.
[Maintained Rejection 06]
Claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 9,125,882 B2 (Sep. 8, 2015; cited in previous action).
Claim Interpretation: The applicable claim interpretation has been set forth above in a separate section entitled “Claim Interpretations” above, and/or discussed in preceding rejections. Those interpretations and discussions are incorporated herein unless otherwise explicitly stated. As noted above, the product-by-process language of amended claim 1 is presumed to be fully satisfied by all embodiments comprising the equivalents of 20 mg/mL ZP1848-acetate (SEQ ID NO: 1), 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and having a pH of 7.0. Additional claim interpretations are discussed below.
The primary reference overlaps in scope with the instant claims as explained below (see, e.g., US’882 at claims 1-3 and 5-7, passim). Regarding the GLP-2 analog structure of ZP1848 as recited at instant claims 1, 5, 7, 9, 19, 29-30, and 73, the primary reference claims pharmaceutical compositions comprising salts of SEQ ID NO: 36 (compare US’882 at claims 1-3 and 5-7, SEQ ID NO: 36 with instant claim 1 and ZP1848 of instant SEQ ID NO: 1, showing 100% identity). Notably, the sequence recited in the claims of US’882 is ZP1848 (compare US’882 at col. 21. at lines 1-5 at SEQ ID NO: 36 identified as “1848” and claims 1-3 and 5-7 with instant claim 1 and instant SEQ ID NO: 1, showing 100% identity).
The disclosure of the primary reference differs from the instant claims as follows: Although the prior art reference directs artisans to make and use pharmaceutical formulations comprising a GLP-2 analog like “1848”, it differs from the instant claims because it does not explicitly reduce to practice a formulation of the GLP-2 analog of “1848” that comprises 20 mg/mL “1848”, 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, has a pH of 7.0, and contains arginine in an amount sufficient “to provide a formulation having a pH of about 6.6 to about 7.4” as presently claimed.
However, the prior art reference explicitly teaches, discloses, and directs artisans to utilize pharmaceutically acceptable compositions of the recited GLP-2 analog “1848” (SEQ ID NO: 36) (see, e.g., US’882 at claims 1-3 and 5-7); and specifically directs artisans to make and use pharmaceutical formulations comprising “most preferably” 10-30 mg/mL of GLP-2 analogue, “most preferably” 5 to 50 mM L-histidine, “most preferably” mannitol at 100 mM to 230 mM (and “preferably” 30 to 300 mM), arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at “most preferably” 0.5 to 50 mM in an aqueous solution, wherein the acetic acid would be reasonably inferred to be the equivalent of an acetate salt of the GLP-2 analogue in the product-by-process language of instant claim 1 (see, e.g., US’882 at col 31 at lines 35-60; see also id. at col. 32 at lines 10-35).
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): The invention is obvious because it is the combination of the exact prior art elements taught by the primary reference (i.e., known GLP-2 analogue, histidine buffer, mannitol, arginine for pH of 6.7 to 7.3, and acetic acid to obtain acetate salts) according to known methods of making GLP-2 analogue containing pharmaceutical compositions as claimed by US’882, to yield predictable results, namely pharmaceutical compositions comprising 10-30 mg/mL of GLP-2 analogue “1848”, 5 to 50 mM L-histidine, Mannitol at 100 mM to 230 mM, arginine up to 200 mM with a pH of 6.7 to 7.3, and acetic acid at 0.5 to 50 mM in an aqueous solution (see, e.g., MPEP § 2143(I)(A), (G); 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”). Furthermore, each component merely performs the same 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 in the art to make a pharmaceutical formulation comprising prior art components at known concentration ranges to obtain products exactly as taught and disclosed by the prior art.
Accordingly, claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected.
[Maintained Rejection 07]
Claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 9,580,487 B2 (Feb. 28, 2017; cited in previous action).
Claim Interpretation: The applicable claim interpretation has been set forth above in a separate section entitled “Claim Interpretations” above, and/or discussed in preceding rejections. Those interpretations and discussions are incorporated herein unless otherwise explicitly stated. As noted above, the product-by-process language of amended claim 1 is presumed to be fully satisfied by all embodiments comprising the equivalents of 20 mg/mL ZP1848-acetate (SEQ ID NO: 1), 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and having a pH of 7.0. Additional claim interpretations are discussed below.
The primary reference overlaps in scope with the instant claims as explained below (see, e.g., US’487 at claims 1-4 and 6-20, passim). Regarding the GLP-2 analog structure of ZP1848 recited at instant claims 1, 5, 7, 9, 19, 29-30, and 73, the primary reference claims methods of utilizing pharmaceutical compositions comprising SEQ ID NO: 36 (compare US’487 at claims 1-4 and 6-20, SEQ ID NO: 36 with instant claim 1 and ZP1848 of instant SEQ ID NO: 1, showing 100% identity). Notably, the sequence recited in the claims of US’487 (i.e., SEQ ID NO: 36, “Compound 1848”) is ZP1848 (compare US’487 at col. 21. at lines 1-45 at SEQ ID NO: 36 identified as “1848” and claims 1-4 and 6-20 with instant claim 1 and instant SEQ ID NO: 1, showing 100% identity).
The disclosure of the primary reference differs from the instant claims as follows: Although the prior art reference directs artisans to make and use pharmaceutical formulations comprising a GLP-2 analog like “1848”, it differs from the instant claims because it does not explicitly reduce to practice a formulation of the GLP-2 analog of “1848” that comprises 20 mg/mL “1848”, 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, has a pH of 7.0, and contains arginine in an amount sufficient “to provide a formulation having a pH of about 6.6 to about 7.4” as presently claimed.
However, the prior art reference explicitly teaches, discloses, and directs artisans to utilize pharmaceutically acceptable compositions of the recited GLP-2 analog “1848” (SEQ ID NO: 36) (see, e.g., US’487 at claims 1-4 and 6-20); and specifically directs artisans to make and use pharmaceutical formulations comprising “most preferably” 10-30 mg/mL of GLP-2 analogue, “most preferably” 5 to 50 mM L-histidine, “most preferably” mannitol at 100 mM to 230 mM (and “preferably” 30 to 300 mM), arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at “most preferably” 0.5 to 50 mM in an aqueous solution, wherein the acetic acid would be reasonably inferred to be the equivalent of an acetate salt of the GLP-2 analogue in the product-by-process language of instant claim 1 (see, e.g., US’487 at col 32 at lines 1-23; see also id. at col. 32 at lines 45-65).
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): The invention is obvious because it is the combination of the exact prior art elements taught by the primary reference (i.e., known GLP-2 analogues, histidine buffer, mannitol, arginine for pH of 6.7 to 7.3, and acetic acid to obtain acetate salts) according to known methods of making GLP-2 analogue containing pharmaceutical compositions as claimed by US’487, to yield predictable results, namely pharmaceutical compositions comprising 10-30 mg/mL of GLP-2 analogue “1848”, 5 to 50 mM L-histidine, Mannitol at 100 mM to 230 mM, arginine up to 200 mM with a pH of 6.7 to 7.3, and acetic acid at 0.5 to 50 mM in an aqueous solution, which would be predictably and expectedly usable in the methods claimed by US’487 (see, e.g., MPEP § 2143(I)(A), (G); 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”). Furthermore, each component merely performs the same 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 in the art to make a pharmaceutical formulation comprising prior art components at known concentration ranges to obtain products exactly as taught and disclosed by the prior art.
Accordingly, claims 1, 5, 7, 9, 19, 29-30, and 73 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.
[Maintained Rejection 08]
Claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 8,163,696 B2 (Apr. 24, 2012; cited in previous action) in view of WO2006/117565A1 (Nov. 9, 2006; Larsen et al.; cited in previous action).
Claim Interpretation: The applicable claim interpretation has been set forth above in a separate section entitled “Claim Interpretations” above, and/or discussed in preceding rejections. Those interpretations and discussions are incorporated herein unless otherwise explicitly stated. As noted above, the product-by-process language of amended claim 1 is presumed to be fully satisfied by all embodiments comprising the equivalents of 20 mg/mL ZP1848-acetate (SEQ ID NO: 1), 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and having a pH of 7.0. Additional claim interpretations are discussed below.
The primary reference overlaps in scope with the instant claims as explained below (see, e.g., US’696 at claims 1-4, passim). Regarding the GLP-2 analog structure recited at instant claims 1, 5, 7, 9, 11, 19, 29-30, and 73, the primary reference claims methods necessitating the existence of pharmaceutical compositions comprising SEQ ID NO: 36, wherein R1 is H and R2 is NH2 (compare US’696 at claims 1-4, SEQ ID NO: 36 with instant claim 1 and ZP1848 or instant SEQ ID NO: 1, showing 100% identity). In sum, US’696 directs artisans to make and use pharmaceutical formulations comprising the exact same GLP-2 analog presently claimed.
The disclosure of the primary reference differs from the instant claims as follows: Although the primary reference claims methods necessitating the existence of pharmaceutical formulations comprising the same GLP-2 analog now claimed, the primary reference does not explicitly claim embodiments wherein the GLP-2 analog of “1848” (i.e., SEQ ID NO: 36 of the primary reference) is present at 20 mg/mL in combination with 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and contains arginine in an amount sufficient “to provide a formulation having a pH of about 6.6 to about 7.4” as presently claimed.
However, such pharmaceutical formulations were already known and taught in the prior art for use with the same exact GLP-2 analog of “1848” and therefore such differences do not render the pending claim scope patentably distinct over the prior art in view of an obviousness-type rationale. Specifically, the prior art reference of WO’565 explicitly pertains to GLP-2 formulations, which explicitly apply to the same, exact GLP-2 analog of “1848” (see, e.g., WO’565 at 20 at lines 35-40; compare id with primary reference at claims, noting “1848” refers to the same sequence, notably SEQ ID NO: 36). This is pertinent because WO’565 teaches and discloses “stable” formulations (see, e.g., WO’565 at 17 at lines 9-19, 30 at lines 7-12; see also id. at 2 at lines 26-30, 28 at lines 15-20), suitable for administration to patients (see, e.g., WO’565 at 31 at lines 4-30), including prior art pharmaceutical formulations comprising “most preferably” 10-30 mg/mL of GLP-2 analogue, “most preferably” 5 to 50 mM L-histidine, “most preferably” mannitol at 100 mM to 230 mM (and “preferably” 30 to 300 mM), arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at “most preferably” at 0.5 to 50 mM in an aqueous solution, wherein the acetic acid would be reasonably inferred to be the equivalent of an acetate salt of the GLP-2 analogue in the product-by-process language of instant claim 1 (see, e.g., WO’565 at p. 32 at line 30 to page 33 at line 10; see also id. at p. 33 at lines 24-38). In sum, formulations comprising the GLP-2 analog of “1848” (i.e., SEQ ID NO: 36 of the primary reference) at 20 mg/mL in combination with 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and containing arginine in an amount sufficient “to provide a formulation having a pH of about 6.6 to about 7.4” fall well inside the ranges of prior art embodiments explicitly taught for use with the GLP-2 analog of “1848” (see, e.g., WO’565 at p. 32 at line 30 to page 33 at line 10; see also id. at p. 33 at lines 24-38; 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”). Accordingly, the explicit recitation of known parameters for such pharmaceutical formulations fail to render the instant claims patentably distinct from the issued claims of the primary reference.
Therefore, in view of the primary reference and WO’565, a person of ordinary skill in the art would conclude that the invention defined in instant claims 1, 5, 7, 9, 11, 19, 29-30, and 73 would have been an obvious variation of the invention defined by the claims of the primary reference because the claims of the primary reference necessarily require the existence and usage of “pharmaceutical compositions” suitable for administration to patients comprising the GLP-2 analog of “1848”, and WO’565 teaches and discloses such pharmaceutical formulations comprising the same exact GLP-2 analog at 10-30 mg/mL, in combination with 5 to 50 mM L-histidine, mannitol at 100 mM to 230 mM, arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at 0.5 to 50 mM in an aqueous solution were routinely utilized and known in the GLP-2 analog arts. Accordingly, the invention is an obvious variation of the issued claims of the primary reference, because, as established in view of the secondary reference, the differences at issue were explicitly taught and disclosed in the art for GLP-2 analog pharmaceutical compositions (see also analogous rationales supporting a determination of obviousness as set forth at MPEP § 2143(I)(A), (B), (G); 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”). Accordingly, the instant claims are not directed to a patentably distinct invention.
Therefore, claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected.
[Maintained Rejection 09]
Claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 8,263,552 B2 (Sept. 11, 2012; cited in previous action) in view of WO2006/117565A1 (Nov. 9, 2006; Larsen et al.; cited in previous action).
Claim Interpretation: The applicable claim interpretation has been set forth above in a separate section entitled “Claim Interpretations” above, and/or discussed in preceding rejections. Those interpretations and discussions are incorporated herein unless otherwise explicitly stated. As noted above, the product-by-process language of amended claim 1 is presumed to be fully satisfied by all embodiments comprising the equivalents of 20 mg/mL ZP1848-acetate (SEQ ID NO: 1), 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and having a pH of 7.0. Additional claim interpretations are discussed below.
The primary reference overlaps in scope with the instant claims as explained below (see, e.g., US’552 at claims 1-8, passim). Regarding the GLP-2 analog structure recited at instant claims 1, 5, 7, 9, 19, 29-30, and 73, the primary reference claims pharmaceutical compositions comprising SEQ ID NO: 36, wherein R1 is H and R2 is NH2 (compare US’552 at claims 1-8, SEQ ID NO: 36 with instant claim 1 and ZP1848 or instant SEQ ID NO: 1, showing 100% identity). In sum, the primary reference directs artisans to make and use pharmaceutical formulations comprising the exact same GLP-2 analog as presently claimed.
The disclosure of the primary reference differs from the instant claims as follows: Although the primary reference claims pharmaceutical formulations comprising the same GLP-2 analog now claimed, the primary reference does not explicitly claim embodiments wherein the GLP-2 analog of “1848” (i.e., SEQ ID NO: 36 of the primary reference) is present at “about 5 mg/mL to about 25 mg/mL” in combination with “about 5 mM to about 50 mM” histidine buffer, “about 90 to about 360 mM” mannitol, 20.3 to 37.3 mM acetate, and contains arginine in an amount sufficient “to provide a formulation having a pH of about 6.6 to about 7.4” as presently claimed.
However, such pharmaceutical formulations were already known and taught in the prior art for use with the same exact GLP-2 analog of “1848” and therefore such differences do not render the pending claim scope patentably distinct over the prior art in view of an obviousness-type rationale. Specifically, the prior art reference of WO’565 explicitly pertains to GLP-2 formulations, which explicitly apply to the same, exact GLP-2 analog of “1848” (see, e.g., WO’565 at 20 at lines 35-40; compare id with primary reference at claims, noting “1848” refers to the same sequence, notably SEQ ID NO: 36). This is pertinent because WO’565 teaches and discloses “stable” formulations (see, e.g., WO’565 at 17 at lines 9-19, 30 at lines 7-12; see also id. at 2 at lines 26-30, 28 at lines 15-20), suitable for administration to patients (see, e.g., WO’565 at 31 at lines 4-30), including prior art pharmaceutical formulations comprising “most preferably” 10-30 mg/mL of GLP-2 analogue, “most preferably” 5 to 50 mM L-histidine, “most preferably” mannitol at 100 mM to 230 mM (and “preferably” 30 to 300 mM), arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at “most preferably” at 0.5 to 50 mM in an aqueous solution, wherein the acetic acid would be reasonably inferred to be the equivalent of an acetate salt of the GLP-2 analogue in the product-by-process language of instant claim 1 (see, e.g., WO’565 at p. 32 at line 30 to page 33 at line 10; see also id. at p. 33 at lines 24-38). In sum, formulations comprising the GLP-2 analog of “1848” (i.e., SEQ ID NO: 36 of the primary reference) at 20 mg/mL in combination with 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and containing arginine in an amount sufficient “to provide a formulation having a pH of about 6.6 to about 7.4” fall well inside the ranges of prior art embodiments explicitly taught for use with the GLP-2 analog of “1848” (see, e.g., WO’565 at p. 32 at line 30 to page 33 at line 10; see also id. at p. 33 at lines 24-38; 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”). Accordingly, the explicit recitation of known parameters for such pharmaceutical formulations fail to render the instant claims patentably distinct from the issued claims of the primary reference.
Therefore, in view of the primary reference and WO’565, a person of ordinary skill in the art would conclude that the invention defined in instant claims 1, 5, 7, 9, 11, 19, 29-30, and 73 would have been an obvious variation of the invention defined by the claims of the primary reference because the claims of the primary reference necessarily require the existence and usage of “pharmaceutical compositions” suitable for administration to patients comprising the GLP-2 analog of “1848”, and WO’565 teaches and discloses such pharmaceutical formulations comprising the same exact GLP-2 analog at 10-30 mg/mL, in combination with 5 to 50 mM L-histidine, mannitol at 100 mM to 230 mM, arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at 0.5 to 50 mM in an aqueous solution were routinely utilized and known in the GLP-2 analog arts. Accordingly, the invention is an obvious variation of the issued claims of the primary reference, because, as established in view of the secondary reference, the differences at issue were explicitly taught and disclosed in the art for GLP-2 analog pharmaceutical compositions (see also analogous rationales supporting a determination of obviousness as set forth at MPEP § 2143(I)(A), (B), (G); 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”). Accordingly, the instant claims are not directed to a patentably distinct invention.
Therefore, claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected.
[Maintained Rejection 10]
Claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 5-7 of U.S. Patent No. 9,125,882 B2 (Sep. 8, 2015; cited in previous action) in view of WO2006/117565A1 (Nov. 9, 2006; Larsen et al. ; cited in previous action).
Claim Interpretation: The applicable claim interpretation has been set forth above in a separate section entitled “Claim Interpretations” above, and/or discussed in preceding rejections. Those interpretations and discussions are incorporated herein unless otherwise explicitly stated. As noted above, the product-by-process language of amended claim 1 is presumed to be fully satisfied by all embodiments comprising the equivalents of 20 mg/mL ZP1848-acetate (SEQ ID NO: 1), 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and having a pH of 7.0. Additional claim interpretations are discussed below.
The primary reference overlaps in scope with the instant claims as explained below (see, e.g., US’882 at claims 1-3 and 5-7). Regarding the GLP-2 analog structure recited at instant claims 1, 5, 7, 9, 19, 29-30, and 73, the primary reference claims pharmaceutical compositions comprising SEQ ID NO: 36, wherein R1 is H and R2 is NH2 (compare US’882 at claims 1-3 and 5-7, SEQ ID NO: 36 with instant claim 1 and ZP1848 or instant SEQ ID NO: 1, showing 100% identity). In sum, the primary reference directs artisans to make and use pharmaceutical formulations comprising the exact same GLP-2 analog as presently claimed.
The disclosure of the primary reference differs from the instant claims as follows: Although the primary reference claims pharmaceutical formulations comprising the same GLP-2 analog now claimed, the primary reference does not explicitly claim embodiments wherein the GLP-2 analog of “1848” (i.e., SEQ ID NO: 36 of the primary reference) is present at “about 5 mg/mL to about 25 mg/mL” in combination with “about 5 mM to about 50 mM” histidine buffer, “about 90 to about 360 mM” mannitol, 20.3 to 37.3 mM acetate, and contains arginine in an amount sufficient “to provide a formulation having a pH of about 6.6 to about 7.4” as presently claimed.
However, such pharmaceutical formulations were already known and taught in the prior art for use with the same exact GLP-2 analog of “1848” and therefore such differences do not render the pending claim scope patentably distinct over the prior art in view of an obviousness-type rationale. Specifically, the prior art reference of WO’565 explicitly pertains to GLP-2 formulations, which explicitly apply to the same, exact GLP-2 analog of “1848” (see, e.g., WO’565 at 20 at lines 35-40; compare id with primary reference at claims, noting “1848” refers to the same sequence, notably SEQ ID NO: 36). This is pertinent because WO’565 teaches and discloses “stable” formulations (see, e.g., WO’565 at 17 at lines 9-19, 30 at lines 7-12; see also id. at 2 at lines 26-30, 28 at lines 15-20), suitable for administration to patients (see, e.g., WO’565 at 31 at lines 4-30), including prior art pharmaceutical formulations comprising “most preferably” 10-30 mg/mL of GLP-2 analogue, “most preferably” 5 to 50 mM L-histidine, “most preferably” mannitol at 100 mM to 230 mM (and “preferably” 30 to 300 mM), arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at “most preferably” at 0.5 to 50 mM in an aqueous solution, wherein the acetic acid would be reasonably inferred to be the equivalent of an acetate salt of the GLP-2 analogue in the product-by-process language of instant claim 1 (see, e.g., WO’565 at p. 32 at line 30 to page 33 at line 10; see also id. at p. 33 at lines 24-38). In sum, formulations comprising the GLP-2 analog of “1848” (i.e., SEQ ID NO: 36 of the primary reference) at 20 mg/mL in combination with 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and containing arginine in an amount sufficient “to provide a formulation having a pH of about 6.6 to about 7.4” fall well inside the ranges of prior art embodiments explicitly taught for use with the GLP-2 analog of “1848” (see, e.g., WO’565 at p. 32 at line 30 to page 33 at line 10; see also id. at p. 33 at lines 24-38; 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”). Accordingly, the explicit recitation of known parameters for such pharmaceutical formulations fail to render the instant claims patentably distinct from the issued claims of the primary reference.
Therefore, in view of the primary reference and WO’565, a person of ordinary skill in the art would conclude that the invention defined in instant claims 1, 5, 7, 9, 11, 19, 29-30, and 73 would have been an obvious variation of the invention defined by the claims of the primary reference because the claims of the primary reference necessarily require the existence and usage of “pharmaceutical compositions” suitable for administration to patients comprising the GLP-2 analog of “1848”, and WO’565 teaches and discloses such pharmaceutical formulations comprising the same exact GLP-2 analog at 10-30 mg/mL, in combination with 5 to 50 mM L-histidine, mannitol at 100 mM to 230 mM, arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at 0.5 to 50 mM in an aqueous solution were routinely utilized and known in the GLP-2 analog arts. Accordingly, the invention is an obvious variation of the issued claims of the primary reference, because, as established in view of the secondary reference, the differences at issue were explicitly taught and disclosed in the art for GLP-2 analog pharmaceutical compositions (see also analogous rationales supporting a determination of obviousness as set forth at MPEP § 2143(I)(A), (B), (G); 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”). Accordingly, the instant claims are not directed to a patentably distinct invention.
Therefore, claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected.
[Maintained Rejection 11]
Claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 6-20 of U.S. Patent No. 9,580,487 B2 (Feb. 28, 2017; cited in previous action) in view of WO2006/117565A1 (Nov. 9, 2006; Larsen et al.; cited in previous action).
Claim Interpretation: The applicable claim interpretation has been set forth above in a separate section entitled “Claim Interpretations” above, and/or discussed in preceding rejections. Those interpretations and discussions are incorporated herein unless otherwise explicitly stated. As noted above, the product-by-process language of amended claim 1 is presumed to be fully satisfied by all embodiments comprising the equivalents of 20 mg/mL ZP1848-acetate (SEQ ID NO: 1), 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and having a pH of 7.0. Additional claim interpretations are discussed below.
The primary reference overlaps in scope with the instant claims as explained below (see, e.g., US’487 at claims 1-4 and 6-20, passim). Regarding the GLP-2 analog structure recited at instant claims 1, 5, 7, 9, 19, 29-30, and 73, the primary reference claims pharmaceutical compositions comprising SEQ ID NO: 36 (compare US’487 at claims 1-4 and 6-20, SEQ ID NO: 36 with instant claim 1 and ZP1848 or instant SEQ ID NO: 1, showing 100% identity). In sum, the primary reference directs artisans to make and use pharmaceutical formulations comprising the exact same GLP-2 analog as presently claimed.
The disclosure of the primary reference differs from the instant claims as follows: Although the primary reference claims methods necessitating making and using pharmaceutical formulations comprising the same GLP-2 analog now claimed, the primary reference does not explicitly claim embodiments wherein the GLP-2 analog of “1848” (i.e., SEQ ID NO: 36 of the primary reference) is present at “about 5 mg/mL to about 25 mg/mL” in combination with “about 5 mM to about 50 mM” histidine buffer, “about 90 to about 360 mM” mannitol, 20.3 to 37.3 mM acetate, and contains arginine in an amount sufficient “to provide a formulation having a pH of about 6.6 to about 7.4” as presently claimed.
However, such pharmaceutical formulations were already known and taught in the prior art for use with the same exact GLP-2 analog of “1848” and therefore such differences do not render the pending claim scope patentably distinct over the prior art in view of an obviousness-type rationale. Specifically, the prior art reference of WO’565 explicitly pertains to GLP-2 formulations, which explicitly apply to the same, exact GLP-2 analog of “1848” (see, e.g., WO’565 at 20 at lines 35-40; compare id with primary reference at claims, noting “1848” refers to the same sequence, notably SEQ ID NO: 36). This is pertinent because WO’565 teaches and discloses “stable” formulations (see, e.g., WO’565 at 17 at lines 9-19, 30 at lines 7-12; see also id. at 2 at lines 26-30, 28 at lines 15-20), suitable for administration to patients (see, e.g., WO’565 at 31 at lines 4-30), including prior art pharmaceutical formulations comprising “most preferably” 10-30 mg/mL of GLP-2 analogue, “most preferably” 5 to 50 mM L-histidine, “most preferably” mannitol at 100 mM to 230 mM (and “preferably” 30 to 300 mM), arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at “most preferably” at 0.5 to 50 mM in an aqueous solution, wherein the acetic acid would be reasonably inferred to be the equivalent of an acetate salt of the GLP-2 analogue in the product-by-process language of instant claim 1 (see, e.g., WO’565 at p. 32 at line 30 to page 33 at line 10; see also id. at p. 33 at lines 24-38). In sum, formulations comprising the GLP-2 analog of “1848” (i.e., SEQ ID NO: 36 of the primary reference) at 20 mg/mL in combination with 15 mM histidine buffer, 230 mM mannitol, 20.3 to 37.3 mM acetate, and containing arginine in an amount sufficient “to provide a formulation having a pH of about 6.6 to about 7.4” fall well inside the ranges of prior art embodiments explicitly taught for use with the GLP-2 analog of “1848” (see, e.g., WO’565 at p. 32 at line 30 to page 33 at line 10; see also id. at p. 33 at lines 24-38; 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”). Accordingly, the explicit recitation of known parameters for such pharmaceutical formulations fail to render the instant claims patentably distinct from the issued claims of the primary reference.
Therefore, in view of the primary reference and WO’565, a person of ordinary skill in the art would conclude that the invention defined in instant claims 1, 5, 7, 9, 19, 29-30, and 73 would have been an obvious variation of the invention defined by the claims of the primary reference because the claims of the primary reference necessarily require the existence and usage of “pharmaceutical compositions” suitable for administration to patients comprising the GLP-2 analog of “1848”, and WO’565 teaches and discloses such pharmaceutical formulations comprising the same exact GLP-2 analog at 10-30 mg/mL, in combination with 5 to 50 mM L-histidine, mannitol at 100 mM to 230 mM, arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at 0.5 to 50 mM in an aqueous solution were routinely utilized and known in the GLP-2 analog arts. Accordingly, the invention is an obvious variation of the issued claims of the primary reference, because, as established in view of the secondary reference, the differences at issue were explicitly taught and disclosed in the art for GLP-2 analog pharmaceutical compositions (see also analogous rationales supporting a determination of obviousness as set forth at MPEP § 2143(I)(A), (B), (G); 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”). Accordingly, the instant claims are not directed to a patentably distinct invention.
Therefore, claims 1, 5, 7, 9, 19, 29-30, and 73 are rejected.
Response to Arguments
Applicant's arguments filed 2/12/2026 have been fully considered but they are not persuasive. Notably, in view of the numerous maintained rejections, the Examiner’s prior response of record remains pertinent and is incorporated herein. Additional applicable arguments are addressed below.
Rejections under 35 U.S.C. § 103
It is the Examiner’s understanding that Applicant traverses all rejections under 35 USC § 103 collectively (see, e.g., Reply filed 2/12/2026 at p. 5 at § “35 U.S.C. § 103 Rejection” to p. 9 at 1st partial ¶). Accordingly, such arguments have been addressed collectively below.
Applicant fails to identify, with specificity, what exact reference they are citing in their arguments: Examiner notes that Applicant refers to seven documents “collectively” as “Larsen” (see, e.g., Reply filed 2/12/2026 at 5 at 5th ¶, starting with “The claims stand rejected”), and then subsequently refers to “Larsen” at specific pages and line numbers (see, e.g., Reply filed 2/09/2026 at 6 at final ¶, 7 at 1st ¶). It is unclear what specific document is being referred to by these citations, since the references do not refer to a single reference, and therefore such arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
Applicant’s arguments appear to be premised upon a mischaracterization of the instantly pending claim scope: It is the Examiner’s understanding that Applicant repeatedly refers to an unclaimed invention. For example, Applicant incorrectly alleges that the pending claim scope excludes “exogenous acetic acid . . . except that which originates from the purified drug substance” (see, e.g., Reply filed 2/12/2026 at 6 at 3rd full ¶ starting with “The formulation”; 8 at 1st ¶ referring to “using solely the ZP1848-acetate salt ….refraining from introducing exogenous acetic acid”). This is factually incorrect as no such limitation appears in the claimed invention. Rather, the preamble of claim 1 clearly recites “comprising” language, which is open-ended (see, e.g., MPEP § 2111.03(I)-(II)), and therefore the claim does not, in fact, exclude the addition of exogenous acetic acid, TFA, PEG, etc., etc. Rather, the only limitation regarding acetic acid appears at the proviso of claim 1(i), which limits the “total acetate concentration in the formulation”. Accordingly, the pending claims clearly continue to read upon embodiments that may include exogenously added acetic acid from sources other than the ZP1848-acetate salt. Accordingly, all arguments premised upon an incorrect characterization of the pending claim scope are not persuasive because such arguments fail to distinguish the actual invention being claimed from the prior art of record.
Applicant’s arguments appear to refer to unclaimed limitations: It is the Examiner’s understanding that Applicant is attempting to distinguish the claimed invention relative to the prior art by repeatedly referring to unclaimed limitations (see, e.g., Reply filed 2/12/2026 at 6 at 3rd full ¶ starting with “The formulation”, referring to “the amount of acetate introduced into the formulation upon reconstitution with excipients” and stating that “No exogenous acetic acid is introduced into the solution”; see id. at 7 at final ¶ stating that “The claimed formulations first require a purification step”; see id. at 8 at 1st ¶ suggesting that “alternative acid counterions” are excluded from the instant claim scope; see id. at 8 at 1st ¶ suggesting the claimed invention uses “solely the ZP1948 acetate salt….and refraining from introducing exogenous acetic acid”; see id. at 8 at 2nd ¶ referring to “hydrochloride” counterions; see id. at 8 at 2nd ¶ suggesting that the instant claim scope excludes the presence of “alternative acid counterions” such as “trifluoroacetate”; see id. at 8-9 at bridging ¶ referring to “careful control of the acetate content in the formulation” based upon a “defined acetate counterion ratio”). In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., unclaimed features and unclaimed product-by-process steps identified above) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
The disclosure of the prior art is not limited to exemplified embodiments: It is the Examiner’s understanding that Applicant attempts to limit the disclosure of the prior art to only the “embodied formulations of Larsen” (see, e.g., Reply filed 2/12/2026 at 6 at final ¶). This is not persuasive 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)), including nonpreferred and alternative embodiments beyond disclosed examples and preferred embodiments (see, e.g., MPEP § 2123(II)). Accordingly, arguments premised upon attempts to limit the prior art to exemplified embodiments are not persuasive.
Conclusory statements, speculation, and conjecture inconsistent with the literal teachings of the prior art and evidence of record, unsupported by objective evidence, are not persuasive: It is the Examiner’s understanding that Applicant repeatedly recites conclusory statements unsupported by any objective evidence or supporting citations (see, e.g., Reply filed 2/12/2026 at 6 alleging that “Larsen cannot appreciate….”; at 7 at 1st full ¶ alleging that “Larsen describes that the acetate content of the disclosed formulations is a separate component than the counterion originating from the therapeutic analogue”; at 7 at 1st full ¶ alleging that “Larsen provides no indication that the exclusion of this exogenous acetic acid is ever contemplated”; at 7 at 1st full ¶ alleging that “any guidance in Larsen indicates that the starting material is presumed to be the trifluoroacetate salt form”; at 7 at 1st full ¶ alleging that “all of Larsen's guidance for preparing formulations instructs the addition of large amounts of acetic acid that would be problematic to the formulation viscosity if starting from the acetate salt produced in Example 5 of Larsen”; at 7 at 1st full ¶ alleging that “due to the absence of a salt exchange when using the trifluoroacetate salt as the starting drug substance, the formulations resulting from Larsen's guidance would contain large amounts of trifluoroacetate”; at 7 at final ¶ alleging that “Larsen does not teach the criticality of the salt exchange, and the guidance would instead lead to formulations contaminated with alternative counterions or contain excess acetate, which would affect the stability and consistency of the formulated drug product”; at 7 at final ¶ alleging that “Larsen contains only descriptions of acetic acid being added as a component separate from the GLP-2 analogue; this would result in inconsistent acetate content in Larsen's formulations in comparison to the claimed formulations”; at 8 at first ¶ alleging that “Larsen does not appreciate the importance of the starting material drug substance in preparing the claimed formulations”; at 8 at 2nd full ¶ alleging that “by simply combining the peptides embodied in Larsen directly after purification as the trifluoroacetate salt with acetic acid in solution, these formulations would be contaminated with counterions…”; at 8 at 2nd full ¶ alleging that “the storage longevity of Larsen’s compositions would suffer in comparison to the claimed formulations due to the presence of alternative acid counterions”; at 8-9 at bridging ¶ alleging that “the processes in Larsen do not appreciate the essential steps of salt exchange to prepare the claimed formulations”; etc., etc.1). These conclusory statements amount to unsupported speculation and arguments of counsel. If Applicant means to suggest the existence of skepticism of experts, such evidence should be filed per MPEP § 716.05, as actual evidence is required to establish skepticism of experts. If Applicant is attempting to allege that the prior art is not enabling or inoperable, Applicant is directed to MPEP § 2121(I), which notes that the prior art is presumed fully enabled for all that it discloses, and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). No evidence of inoperability commensurate in scope with the requirements of MPEP § 716.07 have been placed on record at this time. In the absence of objective supporting evidence commensurate in scope with the requirements of MPEP § 716.05 and/or MPEP § 716.07, such statements are understood arguments of counsel unsupported by objective evidence; critically, arguments of counsel cannot take the place of evidence in the record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965), and evidence is required to establish skepticism of experts or otherwise rebut the presumption of operability. Accordingly, such arguments have been fully considered but not found persuasive because no objective evidence showing that the invention, as actually claimed, is patentably distinct or otherwise nonobvious in view of the prior art of record, which teaches formulations comprising the exact same compound presently claimed at the exact same (or overlapping) concentration ranges.
Arguments premised upon alleging that prior art compounds must necessarily comprise additional, unrecited components, wherein only those unrecited components distinguish the claimed invention over the prior art (i.e., a strawman argument), are not persuasive: It is the Examiner’s understanding that Applicant is alleging that the prior art compounds “would contain large amounts of trifluoroacetate” (see, e.g., Reply filed 2/12/2026 at 7 at 1st ¶; see also id. at 7-9), and that “by simply combining the peptides embodied in Larsen directly after purification as the trifluoroacetate salt with acetic acid in solution, these formulations would be contaminated with counterions…” (see, e.g., Reply filed 2/12/2026 at 8 at 2nd full ¶). First, Examiner notes that the actual disclosures of the references at issue do not literally recite or require trifluoroacetate (see, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see esp. id. at 32 at line 34, noting that trifluoroacetate is not recited or mentioned in the list of components for formulations). Second, Examiner notes that, even assuming arguendo that some TFA were present in initial ingredients, an artisan would simply remove the TFA with counterion exchange to obtain the combination of components as actually taught and disclosed by the prior art2. Third, as evidenced by the references of record, counterion-exchange was well-known in the prior art, as evidenced by the prior art references relied upon in the rejections, which exemplifies a method for “counter ion exchange from trifluoroacetate to acetate” after synthesis (see, e.g., WO’565 at p. 44 at lines 25-36; see also US’552 at col 42 at lines 4-25; see also US’882 at col. 44 at lines 4-25):
Counter ion exchange from trifluoroacetate to acetate of Compound 1846. The purified synthetic peptide product of compound 1846 is isolated as a trifluoroacetate salt, due to the presence of trifluoroacetic acid (0, 1 % v/v) in the HPLC buffers used for the purification of the crude synthetic peptide product.
In order to exchange the counter ion trifluoroacetate with acetate, a solution of the peptide was passed through a column packed with strong base ion exchange resin on the acetate (Dowex 1 x8). 365 mg Compound 1 is dissolved in 40 ml water. The solution is passed through a column containing 40 ml strong base ion exchange resin on the acetate (Dowex 1x8; capacity 1.33 meq/ml 35 resin). The resin is then washed with 4 x 30 ml water and the eluate is collected and lyophilized resulting in 312 mg acetate salt with a purity according to HPLC analysis of 97%.
Accordingly, the prior art clearly and unambiguously taught and disclosed methods of forming acetate salts of GLP-2 analogues by “exchang[ing] the counter ion trifluoroacetate with acetate”, wherein the GLP-2 analogue was “passed through a column packed with strong base ion exchange resin on acetate”, and following washing steps, “the eluate is collected and lyophilized” (see, e.g., WO’565 at p. 44 at lines 25-36; see also US’552 at col 42 at lines 4-25; see also US’882 at col. 44 at lines 4-25). Fourth, as evidenced by the Roux et al.3 document cited by the Applicant (see, e.g., Reply filed 2/12/2026 at 8 at 2nd full ¶), TFA counterion exchange with acetate was routine in the art (see, e.g., Roux et al. at title, abs, passim). The Roux et al. reference and Applicant’s reliance upon it is further discussed, below, in a separate paragraph. In sum, misrepresentations of the prior art teachings by alleging that the prior art required additional, unrecited components is not persuasive, because the prior art provides literal guidance to formulations lacking such additional components, and because it was well-within the ordinary skill in the prior art to purify compounds and remove unwanted components in order to make and use the exact combinations of components disclosed by the prior art references at issue, exactly as discussed in the maintained rejections above. Accordingly, all arguments premised upon alleging that an unclaimed invention is distinguishable from an Applicant-altered version of the prior art, wherein the Applicant-alterations are directly contradictory to the literal disclosures of the prior art, fail to satisfy comply with 37 CFR 1.111(b) because the arguments do not specifically identify how the language of the instant claims (as actually claimed) patentably distinguish the claimed invention over the explicit teachings of the prior art of record.
The Examiner’s rationale supporting a determination of obviousness differs from the Applicant’s rationale for arriving at the instantly claimed invention: It is the Examiner’s understanding that Applicant had a different reason for arriving at the instantly claimed invention that differs from the Examiner’s rationales (see, e.g., Reply filed 2/12/2026 at 7 at final ¶ referring to “stability of the formulation” and “viscosity of the solution”; see id. at 8 at 1st full ¶ referring to “acceptable viscosity” and “producing a stable ZP1848”; see id. at 8 at 2nd full ¶ referring to storage longevity; see id. at 8-9 at bridging ¶ referring to preventing oligomerization, viscosity, and storage longevity). Examiner notes that this is not persuasive because an examiner may support a determination of obviousness by relying upon a rationale that differs from the Applicant’s rationale (see, e.g., MPEP § 2144(IV)). Here, the Examiner’s rationales are explicitly identified in the rejection (e.g., MPEP § 2143(I)(A), (G); see also MPEP § 2144.05(I),), but Applicant fails to address or specifically dispute these rationales supporting a determination of obviousness. If Applicant is alleging that they have recognized another advantage which would flow naturally from following the suggestion of the prior art, Examiner notes that this 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).
Arguments premised upon the Moller Declaration filed 2/12/2026: It is the Examiner’s understanding that Applicant refers to and relies upon the Moller Declaration in support of some statements (see, e.g., Reply filed 2/12/2026 at 7 at final ¶, referring to the Declaration and referring to “Results obtained by the Applicant directly demonstrate how Larsen’s guidance does not yield the claimed formulations”; 8 at 1st ¶ to 8 at 2nd full ¶). The Moller Declaration has been fully considered but not found persuasive for reasons set forth in a separate section below, and therefore all arguments depending upon the Moller Declaration are not persuasive (see discussion below).
Arguments premised upon the Villadsen Declaration filed 1/15/2025: It is the Examiner’s understanding that Applicant attempts to rely upon portions of the Villadsen Declaration filed 1/15/2025 (see, e.g., Reply filed 2/12/2026 at 8 at 2nd ¶, stating “As demonstrated . . . in the previous affidavit”). First, the prior declaration was fully considered but not found persuasive for reasons of record, which have not been addressed by Applicant, and those reasons are incorporated herein (see, e.g., Action mailed 5/14/2025 at 48-62). Second, in the Declaration filed 2/12/2026 by Moller, the Declarant now admits that “these earlier statements were determined to be incorrect” (see, e.g., Dec. filed 2/12/2026 at ¶3), but fails to identify, with specificity, which statements were “incorrect”. Accordingly, as the Applicant’s own Declarant has stated that unspecified statements were “incorrect”, the prior declaration is not unambiguously reliable in the absence of clarification of which statements were or were not “incorrect”. In sum, arguments attempting to rely upon the prior declaration filed 1/15/2025 have been fully considered but are not found persuasive for reasons previously set forth on record by the Examiner, and because the Declaration filed 2/12/2026 admits that the prior declaration contained unspecified, “incorrect” statements.
Applicant mistakenly states that “the results obtained by the Applicant directly demonstrate this to be untrue”, but fails to actually identify any such “results” demonstrating any comparison of the claimed invention with the prior art: It is the Examiner’s understanding that Applicant alleges that combinations of the prior art components of L-histidine, L-Arginine, Mannitol, acetic acid from 0.5 to 50 mM, with a GLP-2 analogue at 10 to 30 mg/mL, and a pH of 6.7 to 7.3, exactly as taught by the prior art4, would not yield the instantly claimed invention because “the results obtained by the Applicant directly demonstrate this to be untrue” (see, e.g., Reply filed 2/12/2026 at 8 at 3rd ¶ to 9 at 1st partial ¶). This argument is not persuasive largely for reasons discussed above: First, no such “results” have actually been shown or specifically identified, and therefore such assertions are factually incorrect. Second, as explained above, Applicant appears to mischaracterize the pending claim scope, which is open-ended (“comprising” language is used), and patentability of a product “does not depend on its method of production” (see, e.g., MPEP § 2113(I)-(II)). Third, as explained above, Applicant appears to mischaracterize the teachings of the prior art, by falsely assuming additional components must be present although literally absent from the prior art disclosure (e.g., TFA)5. Fourth, any proffered data using added TFA to demonstrate that embodiments having added TFA do not result in the instantly claimed invention fails to provide any meaningful comparison with the closest prior art of record as actually disclosed in the prior art, because the closest prior art of record does not teach, suggest, or require TFA to be present6. Fifth, as explained above, any arguments premised upon the presence of TFA or other impurities not taught by the prior art, which presume an artisan would be non-enabled or otherwise unable to readily detect and remove TFA and other impurities, is factually incorrect as established by the prior art of record, which explicitly teaches counterion exchanges7, and is factually incorrect as established by Roux et al.8, which was cited by the Applicant (see, e.g., Reply filed 2/12/2026 at 8 at 2nd full ¶) and explicitly teaches that TFA detection and removal was routine in the art circa 2007 (see, e.g., Roux et al. at title, abs, passim). In sum, zero actual results showing that the prior art, as literally taught and disclosed by the references of record, have been placed on record at this time because all such allegations are premised upon numerous false premises. Accordingly, such arguments are not persuasive.
No evidence of unexpected results commensurate in scope with the Requirements of MPEP § 716, § 716.01, and § 716.02 have been placed on record at this time: It is the Examiner’s understanding that Applicant alleges the existence of unexpected results (see, e.g., Reply filed 2/12/2026 at 6 at 1st full ¶ referring to “superior viscosity and a reduced amount of covalent oligomer formation”; 8 at 1st full ¶ referring to “the claimed invention surprisingly overcomes the challenges associated with producing a stable ZP1848 formulation”; 8-9 at bridging ¶ referring to “unprecedented benefits”). However, no such evidence has been placed on record because, to establish such unexpected results, the allegations must be timely and supported by objective evidence (see, e.g., 37 C.F.R. 1.132; see MPEP §§ 716.01, 716.01(a), 716.01(c)); to be of probative value the proffered evidence must be related to the claimed invention (see MPEP §§ 716.01(b), discussing nexus requirement and noting that "[w]here the offered secondary consideration actually results from something other than what is both claimed and novel in the claim, there is no nexus to the merits of the claimed invention"); the evidence must establish that the expected results occur to an unexpected extent (see, e.g., MPEP § 716.02(a)(I)), on the basis of statistically and practically significant evidence (see, e.g., MPEP § 716.02(b)(I)), which is fully explained (see, e.g., MPEP § 716.02(b)(II)), commensurate in scope with the claimed invention (see, e.g., MPEP § 716.02(d)), and wherein a comparison of the claimed invention with the closest prior art of record is provided (see, e.g., MPEP § 716.02(e)). Furthermore, even if evidence satisfying MPEP §§ 716.02, 716.02(a), 716.02(b), 716.02(d), and 716.02(e) is set forth on record, such evidence may not be sufficient to rebut prima facie obviousness because the evidence of expected and unexpected results must be weighed (see, e.g., MPEP § 716.02(c)(I)) and the totality of the record considered (see, e.g., MPEP §§ 716.01(d), 716.02(f)), including teachings in the prior art and evidence of expected results which weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)). Here, the Villadsen Declaration filed 1/15/2025, the Moller Declaration filed 2/12/2026, and the originally filed disclosure have been fully considered, but zero data showing unexpected results commensurate in scope with the Requirements of MPEP § 716, § 716.01, and § 716.02 have been placed on record at this time. Rather, as discussed in the instant response, the prior art of record establishes that TFA removal was routine in the prior art9,10, and the prior art literally teaches and discloses liquid formulations comprising the same exact components at the same or overlapping concentration ranges11, and zero objective evidence of record shows that combinations of such components literally disclosed by the prior art, differ in any material way from the claimed invention.
Applicant appears to allege a difference between the instant disclosure and the prior art, but fails to consider the equivalent guidance provided in the prior art of record: It is the Examiner’s understanding that Applicant alleges that
While the Office asserts that "zero material distinctions between the process taught in the prior art and the process described in the instant disclosure appear to exist," (Office Action, page 61), the peptide used in the claimed invention was converted to the desired acetate salt form by applying a mobile phase during the final chromatographic step with an appropriate concentration of acetic acid and subsequent lyophilization, which produces material distinctions between the claimed formulation and the formulations taught by Larsen
(see, e.g., Reply filed 2/12/2026 at 7 at 1st full ¶).
First, the claimed invention is a product, not a method. Second, the claimed invention does actually recite nor require “applying a mobile phase during the final chromatographic step with an appropriate concentration of acetic acid”, and therefore such arguments are insufficient to materially distinguish the claimed invention over the prior art. Third, such arguments appear to be directed to unclaimed product-by-process limitation pertaining to an unclaimed product that is only pertinent to the claimed invention, in that that unclaimed product is recited in a product-by-process limitation in the instant claim (see, e.g., instant claim 1, noting that the claim is directed to a liquid (solution) formulation “comprising” components, and “formed by combining” the exact components taught by the prior art). Per the MPEP, “even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself” (see, e.g., MPEP § 2113). Fourth, the distinction regarding counterion exchange was well-known and routine in the prior art as evidence by the references set forth in the rejection, which explicitly teaches counterion exchanges12, and is factually incorrect as established by Roux et al.13, which was cited by the Applicant (see, e.g., Reply filed 2/12/2026 at 8 at 2nd full ¶) and explicitly teaches that TFA detection and removal was routine in the art circa 2007 (see, e.g., Roux et al. at title, abs, passim). In sum, arguments alleging that the prior art either required the presence of TFA or otherwise that TFA removal or counterion exchange was not known and well-within the ordinary skill in the art, are not correct or persuasive.
Applicant’s reliance upon Roux et al. is misplaced in the absence of an explanation of the relevance of the document: It is the Examiner’s understanding that Applicant is attempting to rely upon the Roux et al.14 reference to establish the presence of “tightly-bound trifluoroacetate counterion” in the embodiments explicitly taught by the prior art (see, e.g., Reply filed 2/12/2026 at 8 at 2nd full ¶). First, a copy of Roux et al. does not appear to be of record. Examiner has attached a copy to the instant Action to clarify the record. Second, Applicant offers no evidence that the disclosed embodiments of the “Larsen” documents would either require or necessarily contain trifluoroacetate counterions as alleged (see id.). Third, even assuming arguendo that TFA counterions were present, Applicant fails to identify why an artisan could not remove them exactly as taught and disclosed by the “Larsen” documents of record (see, e.g., WO’565 at p. 44 at lines 25-36; see also US’552 at col 42 at lines 4-25; see also US’882 at col. 44 at lines 4-25; wherein each reference discloses a method of forming acetate salts of GLP-2 analogues by “exchang[ing] the counter ion trifluoroacetate with acetate”). Fourth, even assuming arguendo that TFA counterions were present, the reliance upon Roux et al. is misplaced because Roux et al. explicitly identifies that TFA could be an art-recognized problem and explicitly teaches multiple ways to solve that problem (see, e.g. Roux at title, abs, passim). Accordingly, Roux et al. supports a determination that, circa 2007, it was well-within the ordinary skill in the art to remove TFA counterions with acetic acid if desired, using nothing more than extant methodologies circa 2007 (see, e.g. Roux at title, abs; see e.g., MPEP § 2141.03, discussing the level of ordinary skill in the art). In sum, it is unclear why Applicant cites to Roux et al., because Roux does not support their position that TFA must be present in the prior art embodiments, but instead weighs in favor of a determination of obviousness by establishing that TFA counterions could be readily removed by one of ordinary skill in the art.
Applicant appears to allege that unclaimed “steps of salt exchange” are “essential steps” required to prepare the claimed formulations15: Applicant refers to an unclaimed limitation as an “essential step”, wherein the process is performed “without requiring added acetate”, and wherein “the embodied formulations must use the acetate salt of the therapeutic compound” (see, e.g., Reply filed 2/12/2026 at 9 at 1st partial ¶). If such steps are essential, Applicant is directed to MPEP § 2172.01, which explains that such admission would render the pending claim indefinite since such “essential” subject matter is not actually recited in the pending claims. At this time, such steps do not appear “essential” in view of the evidence of record, and a rejection for omitting essential subject matter has not been made. Upon clarification, a rejection may be required and set forth on record in a subsequent action.
There is a reasonable expectation of successfully arriving at a liquid formulation comprising 20 mg/mL ZP1848, 15 mM histidine buffer, 230 mM mannitol, 20.3 mM to 50.8 mM of acetate, and having a pH of 7.0 in view of the prior art: It is the Examiner’s understanding that Applicant is alleging a lack of predictability or otherwise a lack of reasonable expectation of success to arrive at a combination of components literally disclosed by the prior art at a specific pH and concentration range16 (see, e.g., Reply filed 2/12/2026 at 9 at 1st partial ¶ ). This is not persuasive because the Applicant’s assertions do not reflect the proper legal standards for evaluating predictability. MPEP § 2143.02(II) explains that “[o]bviousness does not require absolute predictability”, but instead clarifies that only “at least some degree of predictability is required” (see, e.g., MPEP § 2143.02(II)). Here, the rejection explicitly addresses predictability and reasonable expectation of success, but Applicant fails to address the explicitly identified predicted and expected results set forth in the rejection. Here, the Examiner’s basis for “predictability” is merely based upon the presumption that the prior art is fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). As explained at MPEP § 2143.02, predictability and reasonable expectation of success are satisfied when “all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art”. Here zero evidence of unexpected results commensurate in scope with the requirements of MPEP 716.02 have been set forth on record, all elements of the claimed invention were known in the prior art, one of ordinary skill was fully enabled to combined each component using routine methods in the biochemical arts per the guidance of the primary reference, and the elements would have merely performed their art-recognized, respective functions (see Rejection, above). Accordingly, such arguments are not persuasive.
Allegations of “Lack of predictability”: It is the Examiner’s understanding that Applicant previously attempted to establish “lack of predictability” (see, e.g., Reply filed 1/15/2025 at 10 at 1st full ¶). The test for “predictability” required to establish obviousness is discussed at MPEP § 2143.02. Critically, “conclusive proof of efficacy is not required” and “[o]bviousness does not require absolute predictability” but only “at least some degree of predictability” at “the time the invention was made” (see, e.g., MPEP § 2143.02(I)-(II)). Here, the Examiner has relied upon specific rationales supporting a determination of prima facie obviousness, namely the rationales set forth at MPEP § 2143(I)(A), (G), and MPEP § 2144.05(I). All components presently claimed were individually taught in the prior art, for use together, in formulations suitable for treating diseases and conditions amenable to GLP-2 analogs. More specifically, the prior art explicitly directs artisans to utilize the exact, same GLP-2 analog of ZP1848 presently claimed, and explicitly directs artisans to utilize pharmaceutical formulations comprising “most preferably” 10-30 mg/mL of such GLP-2 analogues, “most preferably” 5 to 50 mM L-histidine, “most preferably” mannitol at 100 mM to 230 mM (and “preferably” 30 to 300 mM), arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3, and acetic acid at “most preferably” at 0.5 to 50 mM in an aqueous solution, wherein the acetic acid would be reasonably inferred to be the equivalent of an acetate salt of the GLP-2 analogue in the product-by-process language of instant claim 1. Accordingly, there is a clear and unambiguous “reasonable expectation of success” that such formulations as taught and suggested by the prior art are fully enabled (see, e.g., MPEP § 2121(I)) for all they claim or disclose (see, e.g., MPEP §§ 2123(I)-(II)), including ZP1848 formulations as presently claimed. Accordingly, arguments alleging lack of predictability are not persuasive in the absence of objective evidence.
Double-Patenting
It is the Examiner’s understanding that Applicant’s basis for traversing the NSDP rejections is to refer to the arguments raised in the section traversing the rejections under 35 USC 103 (see, e.g., Reply filed 2/12/2026 at 9 at § Double Patenting Rejections). This is not persuasive for the reasons provided above, and for reasons previously set forth on record (see, e.g., Action mailed 5/14/2025 at 47 at 1st to 2nd full ¶¶, incorporated herein)
It is the Examiner’s understanding that Applicant does not dispute the merits of the rejections, but instead argues that NSDP rejections based upon a determination of obviousness can be overcome by a showing of unexpected results in view of Otsuka Pharm. Co. v. Sandoz (see, e.g., Reply filed 2/12/2026 at 9 at § Double Patenting Rejections). Even assuming arguendo that this position is correct, no evidence of unexpected results commensurate in scope with the requirements of MPEP § 716, § 716.01, and § 716.02 has been placed on record to date.
A proper response to a rejection for nonstatutory double patenting is filing of a TD, amendment to distinguish from the reference patent, or persuasive arguments as to why the rejection is incorrect. See MPEP 804 I. B. 1. and 804.02 II. A rejection may not be held in abeyance.
Summary
Accordingly, all applicable arguments have been fully considered but not found persuasive for reasons set forth above, below, and previously on record. Therefore, the rejections are maintained as set forth above.
Response to Declarations of Eva Horn Moller under 37 C.F.R. §1.132
The affidavit under 37 CFR 1.132 filed 2/12/2026 is insufficient to overcome the rejections of record. A detailed explanation of why the affidavits or declarations are insufficient is provided below. The legal standards of review and consideration of Declarations under 37 C.F.R. §1.132 are discussed at MPEP § 716.01.
Interest of the Expert in the Outcome of the Case
Per MPEP 716.01(c)(III), in assessing the probative value of an expert opinion, the examiner must consider the interest of the expert in the outcome of the case. Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 227 USPQ 657 (Fed. Cir. 1985), cert, denied, 475 U.S. 1017 (1986). Here, the Declarant is an named inventor, and therefore has a clear interest in the outcome of the case.
Nature of the Matter Sought to be Established
Per MPEP 716.01(c)(III), in assessing the probative value of an expert opinion, the examiner must consider the nature of the matter sought to be established. Ashland Oil, Inc., 776 F.2d 281.
Here, it is unclear what the Declarant seeks to establish, but it is reasonably presumed that the Declaration is set forth to establish either unexpected results commensurate in scope with the requirements set forth at MPEP § 716, § 716.01, and § 716.02, and/or inoperability of the prior art references (see, e.g., Dec. filed 2/12/2026 at ¶¶3-8).
Opinions as to Legal Conclusions
As an initial matter, Examiner notes that per MPEP 716.01(c)(III), any opinions expressed by Declarant regarding legal conclusions are not entitled to any weight. However, the underlying basis for any opinion as to legal conclusions has been fully considered as detailed below.
Acknowledgement That Prior Declaration Contained Incorrect Statements
As an initial matter, the Examiner’s analysis of the prior Declaration of Villadsen filed 1/15/2025 was set forth on record in a previous action (see, e.g., Action mailed 5/14/2025 at pages 48-62). That prior Declaration was found to contain factually incorrect and unsupported statements contradicted by prior art placed on record by the Examiner, and was not found persuasive for reasons of record (see id). In the instant Declaration, the Declarant admits and acknowledges that the prior Declaration contained “earlier statements” that “were determined to be incorrect” (see, e.g., Dec. filed 2/12/2026 at ¶3). Declarant does not specify which statements were “incorrect”, and therefore doubt is cast upon the entire declaration in view of the instant record.
Allegations of Unexpected Results
Per MPEP 716.01(c)(III), in assessing the probative value of an expert opinion, the examiner must consider the presence or absence of factual support for the expert’s opinion. Ashland Oil, Inc., 776 F.2d 281.
The legal requirements for establishing unexpected results are discussed at MPEP §§ 716, 716.01, and 716.02, and are addressed below. With regard to “unexpected results”, MPEP § 716.02 states that “[a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected”.
The Examiner has reviewed the proffered data (see, e.g., Dec. filed 2/12/2026 at Appendix at Part 1 on page 4 and Part 2 on page 5), but notes that it does not satisfy the requirements of MPEP §§ 716, 716.01, and 716.02.
First, per MPEP §716.01(b), the Applicant or patent owner bears the burden of establishing a nexus between the objective evidence of nonobviousness and the claimed invention. Nexus is presumed when the applicant or patent owner shows that the asserted objective evidence of record is tied to a certain product and that product includes the claimed features, and is coextensive with them. Here, there appears to be no nexus with the invention as it is actually claimed because the tested embodiments are not coextensive with the claimed invention, which is not limited to the concentrations, formulation, molar ratios, or pH tested (compare instant claims with Dec. filed 2/12/2026 at Appendix Part 1 at 4, Appendix Part 2 at 5). More specifically, the claimed invention is not a lyophilized solid, but a solution, the claimed invention does not exclude added exogenous acetate or acetic acid because it may “comprise” additional components, and the claimed invention may actually “comprise” TFA. Accordingly, it is unclear what relevance or nexus the tested embodiments share with the invention as actually claimed and recited.
Second, even assuming arguendo that a nexus existed, the proffered data fails to satisfy MPEP § 716.02(b), which states that the burden is on the Declarant to provide evidence establishing that “the differences in results are in fact unexpected and unobvious and of both statistical and practical significance” (see, e.g., MPEP § 716.02(b)(I)). Here, the proffered data is of unknown statistical significance as no statistical analysis is provided, and the practical significance of comparing ZP1846-acetate to ZP1846-trifluoroacetate is unknown because ZP1846-trifluoroacetate is not claimed by the Applicant or taught by the prior art, and furthermore counterion exchange was well-known and routine in the prior art17,18. Notably, ZP1846 is not at issue because ZP1848 is actually claimed and taught by the prior art.
Third, even assuming arguendo that a nexus existed and that the data was of statistical and practical significance, the proffered data fails to satisfy MPEP § 716.02(d) because the proffered data is not commensurate in scope with the claimed invention, which may “comprise” additional components, including TFA. Furthermore, per MPEP § 716.02(d), “the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range”, and “to establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range”, including the concentration of excipients and of ZP1848. Here, zero embodiments of the claimed invention having concentrations of components both inside and outside the claimed ranges, commensurate in scope with the claims, were actually tested and disclosed to have any surprising or unexpected results.
Fourth, although Applicant alleges unexpected results (see, e.g., Reply filed 2/12/2026 at 6 at 1st full ¶ referring to “superior viscosity and a reduced amount of covalent oligomer formation”; 8 at 1st full ¶ referring to “the claimed invention surprisingly overcomes the challenges associated with producing a stable ZP1848 formulation”; 8-9 at bridging ¶ referring to “unprecedented benefits”, etc.), no data pertaining to oligomer formation, viscosity, or longevity of the claimed invention relative to the closest prior art of record (which lacks TFA) is actually tested by the Applicant.
The prior art of record reasonably directs artisans to formulations including GLP-2 analogues such as “1848” (i.e., ZP1848) at “most preferably” 10-30 mg/mL, “most preferably” 5 to 50 mM L-histidine, “most preferably” mannitol at 100 mM to 230 mM (and “preferably” 30 to 300 mM), “most preferably” 0.5 to 50 mM of acetic acid, and containing arginine “up to 200 mM” with a pH of “most preferably” 6.7 to 7.3. Zero discussions showing or explaining how combining the pure ingredients disclosed by the prior art would result in a materially different compound than presently claimed. Notably, arguments alleging that the prior art requires unclaimed components (e.g., TFA) are not reasonable or accurate as explained above since counterion exchange is well-known, and the prior art does not actually teach, suggest, or direct artisans to include TFA in the disclosed formulations. Furthermore, the instant claims may, in fact, “comprise” TFA. Accordingly, arguments that fail to compare the claimed invention with the prior art of record, as actually taught by the prior art, are not persuasive.
Accordingly, per MPEP § 716.02(f), upon weighing the substantial expected benefits supporting a determination of obviousness against the alleged unexpected results that do not satisfy the requirements set forth at MPEP § 716.02, the evidence of record weighs in favor of a determination of obviousness, because the prior art explicitly teaches the same exact components for use in combination at the same or overlapping concentrations19, and zero evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Allegations of Lack of Enablement of the Prior Art
Per MPEP 716.01(c)(III), in assessing the probative value of an expert opinion, the examiner must consider the presence or absence of factual support for the expert’s opinion. Ashland Oil, Inc., 776 F.2d 281.
Here, it is understood that the Declarant seeks to establish that the prior art is not enabling for making unclaimed, solid formulations of ZP1848-acetate “consisting of” components enumerated at amended claim 1(x) within a product-by-process limitation (see, e.g., Dec. filed 2/12/2026 at ¶¶3-8, Appendix at Part 1 on page 4 and Part 2 on page 5).
Prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). The requirements to rebut a presumption of enablement and operability is discussed at MPEP § 716.07. MPEP § 716.07 states that the declaration “must rebut the presumption of operability by a preponderance of the evidence” (see also In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980)). Here, the prior art explicitly teaches the same exact components for use in combination at the same or overlapping concentrations20.
The proffered data pertains to a process for making unclaimed, solid formulations of ZP1848-acetate “consisting of” components enumerated at amended claim 1(x) within a product-by-process limitation (see, e.g., Dec. filed 2/12/2026 at ¶¶3-8, Appendix at Part 1 on page 4 and Part 2 on page 5). As an initial matter, “even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself” (see, e.g., MPEP § 2113). Here, zero evidence of record has established that the claimed invention cannot be made through a materially different process lacking the component of instant claim 1(x), and the prior art explicitly teaches pharmaceutical formulations made by combining the same exact components at the same or overlapping concentrations21.
The proffered data pertains to a process for making unclaimed, solid formulations of ZP1848-acetate “consisting of” components enumerated at amended claim 1(x) within a product-by-process limitation (see, e.g., Dec. filed 2/12/2026 at ¶¶3-8, Appendix at Part 1 on page 4 and Part 2 on page 5). Per MPEP §716.01(b), the Applicant or patent owner bears the burden of establishing a nexus between the objective evidence of nonobviousness and the claimed invention. Nexus is presumed when the applicant or patent owner shows that the asserted objective evidence of record is tied to a certain product and that product includes the claimed features, and is coextensive with them. Here, there appears to be no nexus with the invention as it is actually claimed because the tested embodiments are not coextensive with the claimed invention, which is not limited to the concentrations, formulation, molar ratios, or pH tested (compare instant claims with Dec. filed 2/12/2026 at Appendix Part 1 at 4, Appendix Part 2 at 5). More specifically, the (i) claimed invention is not a lyophilized solid of ZP1846, but a solution of ZP1848, (ii) the claimed invention does not exclude added exogenous acetate or acetic acid because it may “comprise” additional components, and (iii) the claimed invention may actually “comprise” TFA. Accordingly, it is unclear what relevance or nexus the tested embodiments share with the invention as actually claimed and recited.
The proffered data pertains to a process for making unclaimed, solid formulations of ZP1848-acetate “consisting of” components enumerated at amended claim 1(x) within a product-by-process limitation (see, e.g., Dec. filed 2/12/2026 at ¶¶3-8, Appendix at Part 1 on page 4 and Part 2 on page 5). Viewed in the light most favorable to Declarant, it is reasonably understood that Declarant is attempting to argue that the prior art is not enabling for the purification of explicitly enumerated components as taught by the prior art22 or otherwise that the prior art does not enable a perform a counterion exchange of acetate in place of TFA (see id.). This is not persuasive because Declarant shows zero evidence that an artisan could not purify and combine the prior art components in the exact manner disclosed by the prior art23. Furthermore, counterion exchange was well-known and routine in the prior art24,25, and therefore an artisan would be readily understood, enabled, and capable of purifying such components and performing routine prior art methods (see, e.g., 2141.03, discussing the level of skill of an artisan).
In addition, the Examiner has reviewed the instant disclosure. It is noted that the Specification appears to describe lyophilizing a peptide acetate solution to yield a solid with an acetate content (see, e.g., Spec. filed 3/16/2021 at 15 at lines 6-25, p. 29 at lines 10-26), but no special parameters, additives, durations, concentrations, pH values, etc. were disclosed on record (see id). Zero disclosure regarding an essential step of removing all TFA was disclosed (see, e.g., Spec. filed 3/16/2021 at 15 at lines 6-25, p. 29 at lines 10-26). This is pertinent because MPEP § 716.07 requires an additional step of distinguishing the claimed invention relative to the prior art at issue:
Where the affidavit or declaration presented asserts that the reference relied upon is inoperative, the claims represented by applicant must distinguish from the alleged inoperative reference disclosure. In re Crosby, 157 F.2d 198, 71 USPQ 73 (CCPA 1946). See also In re Epstein, 32 F.3d 1559, 31 USPQ2d 1817 (Fed. Cir. 1994) (lack of diagrams, flow charts, and other details in the prior art references did not render them nonenabling in view of the fact that applicant’s own specification failed to provide such detailed information, and that one skilled in the art would have known how to implement the features of the references).
Here, like In re Epstein, arguments alleging that the prior art references did not teach allegedly necessary and required aspects that are also not taught by the instant disclosure are not sufficient to establish lack of operability under MPEP § 716.07, because lack of “other details in the prior art reference [does] not render them nonenabling in view of the fact that applicant’s own specification failed to provide such detailed information”. In sum, if the lack of such details renders the prior art inoperable or non-enabling, it implies that the instant disclosure is also not enabling since it lacks such details of critical and necessary steps identified by the Declarant. Accordingly, per MPEP § 716.07, the lack of details that are also missing from the instant disclosure is not sufficient to satisfy the Declarant’s burden under MPEP § 716.07.
The proffered data pertaining to an unclaimed product recited only in a product-by-process step for obtaining the claimed invention has been fully reviewed. Even assuming arguendo that such data were relevant and supported by the originally filed disclosure, it would be insufficient to establish that the prior art is non-enabling or otherwise inoperable because MPEP § 716.07 explains
Further, since in a patent it is presumed that a process if used by one skilled in the art will produce the product or result described therein, such presumption is not overcome by a mere showing that it is possible to operate within the disclosure without obtaining the alleged product. In re Weber, 405 F.2d 1403, 160 USPQ 549 (CCPA 1969). It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker. The failures of experimenters who have no interest in succeeding should not be accorded great weight. In re Michalek, 162 F.2d 229, 74 USPQ 107 (CCPA 1947); In re Reid, 179 F.2d 998, 84 USPQ 478 (CCPA 1950).
Accordingly, merely showing that it is possible to “operate within the disclosure without obtaining the alleged product” is insufficient to rebut a presumption of operability and enablement. Here, the proffered data is not “within the disclosure” as explained above, and additionally purification of known prior art components and counterion exchange are both well-within the ordinary skill in the art26,27, and therefore it is unclear why an artisan would be unable to combine the exact components taught by the prior art at the exact concentration ranges taught by the prior art to predictably and expectedly obtain the pharmaceutical formulations literally disclosed by the prior art28.
Accordingly, arguments regarding lack of enablement with respect to lyophilized formulations in the prior art have been fully considered but not found persuasive for the reasons discussed above.
Weighing Objective Evidence
Per MPEP § 716.01(d), the ultimate determination of patentability must be based on consideration of the entire record and notes that submission of evidence of patentability does not mandate a conclusion of patentability in and of itself. Accordingly, the Declaration has been fully considered but is not found persuasive because it does not establish unexpected results or lack of enablement commensurate in scope with the requirements set forth in the MPEP. Therefore, in view of the record as a whole, the Declaration is insufficient to overcome the rejections of record, which are maintained as set forth above.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US20070231308A1 (cited in previous action) pertains to related GLP-2 sequences (see, e.g., id. at title, abs, claims).
US20170137487A1 (cited in previous action) pertains to related GLP-2 sequences, and corresponds to abandoned Application 15/411,649.
Krzywinski29 pertains to basic statistical analysis of data, and notes that “Unfortunately, the commonly held view that ‘if the s.e.m. bars do not overlap, the difference between the values is statistically significant’ is incorrect” (see, e.g., Krzywinski at 921 at col II, 921 at Fig. 1. Fig. 3 on 922). Krzywinski teaches that S.E.M. and 95% CI for data with low “n” sizes is substantially large:
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383
321
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(see, e.g., Krzywinski at Fig. 2(b)).
Cumming30 pertains to basic statistical analysis of data, and explains the difference between SE bars and confidence intervals (see, e.g., Cumming at Figs. 4-5 on p. 9, 10 at col 1-3 at § “What is the difference between SE bars and CIs?”, p. 11 at col I-II at § “Rule 6”). As explained by Cummings, “approximate 95% CIs” can be estimated by doubling “standard error of the mean” (SE) “so long as n is 10 or more” (see, e.g., Cummings at 10 at col 3 at 2nd full ¶).
Brown31 pertains to basic statistical analysis of data, and explains that “Quite obviously, the standard deviation, standard error of the mean, standard error of measurement, and standard error of estimate are quite different things” (see, e.g., Brown at 24 at § Conclusion).
MedCalc32 pertains to basic statistical analysis of data, and explains that the STEYX function returns the “standard error of estimation” (SEE) (see, e.g., MedCalc at 1).
OpenLibrary33 pertains to basic statistical analysis of data, and explains that the “standard error of estimate” (SEE) provided by the STEYX function only informs artisans of “how much a dependent variable differs from [a] regression line” (see, e.g., OpenLibrary at 4-5 at bridging ¶), which is useful for identifying whether or not a “linear regression model is” or is not “a good fit for the data” (see, e.g., OpenLibrary at 4).
US9636407B234 establishes that lyophilizing peptides to create peptide-acetate solids was routine in the prior art (see, e.g., US9636407B2 at claims 7-10).
US20060276626A1 discloses drying a peptide-acetate formulation by lyophilizing or spray drying, but obtaining a peptide with acetate (see US20060276626A1 at ¶¶[0098]-[0105]).
Valery35 discloses that acetate powders were commercially available and sold (see, e.g., Valery at title, abs, 2485 at col II at §§ Materials).
Conclusion
No claims are allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RANDALL L BEANE/ Primary Examiner, Art Unit 1654
1 This is not an exhaustive list.
2 See, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see esp. id. at 32 at line 34, noting that trifluoroacetate is not recited or mentioned in the list of components for formulations.
3 Roux et al., Elimination and exchange of trifluoroacetate counter-ion from cationic peptides: a critical evaluation of different approaches. J Pept Sci. 2008 Mar;14(3):354-9. doi: 10.1002/psc.951. PMID: 18035848;
4 See, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see esp. id. at 32 at line 34, noting that trifluoroacetate is not recited or mentioned in the list of components for formulations.
5 See, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see esp. id. at 32 at line 34, noting that trifluoroacetate is not recited or mentioned in the list of components for formulations.
6 See, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see esp. id. at 32 at line 34, noting that trifluoroacetate is not recited or mentioned in the list of components for formulations.
7 See, e.g., WO’565 at p. 44 at lines 25-36; see also US’552 at col 42 at lines 4-25; see also US’882 at col. 44 at lines 4-25; all citations disclosing methods of forming acetate salts of GLP-2 analogues by “exchang[ing] the counter ion trifluoroacetate with acetate”, wherein the GLP-2 analogue was “passed through a column packed with strong base ion exchange resin on acetate”, and following washing steps, “the eluate is collected and lyophilized”.
8 Roux et al., Elimination and exchange of trifluoroacetate counter-ion from cationic peptides: a critical evaluation of different approaches. J Pept Sci. 2008 Mar;14(3):354-9. doi: 10.1002/psc.951. PMID: 18035848;
9 (see, e.g., Reply filed 2/12/2026 at 8 at 2nd full ¶, citing Roux et al., wherein Roux actually supports that TFA detection and removal was routine in the art circa 2007(see, e.g., Roux et al. at title, abs, passim)
10 See, e.g., WO’565 at p. 44 at lines 25-36; see also US’552 at col 42 at lines 4-25; see also US’882 at col. 44 at lines 4-25; all citations disclosing methods of forming acetate salts of GLP-2 analogues by “exchang[ing] the counter ion trifluoroacetate with acetate”, wherein the GLP-2 analogue was “passed through a column packed with strong base ion exchange resin on acetate”, and following washing steps, “the eluate is collected and lyophilized”.
11 See, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see esp. id. at 32 at line 34, noting that trifluoroacetate is not recited or mentioned in the list of components for formulations.
12 See, e.g., WO’565 at p. 44 at lines 25-36; see also US’552 at col 42 at lines 4-25; see also US’882 at col. 44 at lines 4-25; all citations disclosing methods of forming acetate salts of GLP-2 analogues by “exchang[ing] the counter ion trifluoroacetate with acetate”, wherein the GLP-2 analogue was “passed through a column packed with strong base ion exchange resin on acetate”, and following washing steps, “the eluate is collected and lyophilized”.
13 Roux et al., Elimination and exchange of trifluoroacetate counter-ion from cationic peptides: a critical evaluation of different approaches. J Pept Sci. 2008 Mar;14(3):354-9. doi: 10.1002/psc.951. PMID: 18035848;
14 Roux et al., Elimination and exchange of trifluoroacetate counter-ion from cationic peptides: a critical evaluation of different approaches. J Pept Sci. 2008 Mar;14(3):354-9. doi: 10.1002/psc.951. PMID: 18035848;
15 See, e.g., Reply filed 2/12/2026 at 9 at 1st partial ¶.
16 See, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see esp. id. at 32 at line 34, noting that trifluoroacetate is not recited or mentioned in the list of components for formulations.
17 See, e.g., WO’565 at p. 44 at lines 25-36; see also US’552 at col 42 at lines 4-25; see also US’882 at col. 44 at lines 4-25; all citations disclosing methods of forming acetate salts of GLP-2 analogues by “exchang[ing] the counter ion trifluoroacetate with acetate”, wherein the GLP-2 analogue was “passed through a column packed with strong base ion exchange resin on acetate”, and following washing steps, “the eluate is collected and lyophilized”.
18 Roux et al., Elimination and exchange of trifluoroacetate counter-ion from cationic peptides: a critical evaluation of different approaches. J Pept Sci. 2008 Mar;14(3):354-9. doi: 10.1002/psc.951. PMID: 18035848; at title, abs, passim explicitly teaching that TFA detection and removal was routine in the art circa 2007.
19 See, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see esp. id. at 32 at line 34, noting that trifluoroacetate is not recited or mentioned in the list of components for formulations.
20 See, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see esp. id. at 32 at line 34, noting that trifluoroacetate is not recited or mentioned in the list of components for formulations.
21 See, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see esp. id. at 32 at line 34, noting that trifluoroacetate is not recited or mentioned in the list of components for formulations.
22 See, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see esp. id. at 32 at line 34, noting that trifluoroacetate is not recited or mentioned in the list of components for formulations.
23 See, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see esp. id. at 32 at line 34, noting that trifluoroacetate is not recited or mentioned in the list of components for formulations.
24 See, e.g., WO’565 at p. 44 at lines 25-36; see also US’552 at col 42 at lines 4-25; see also US’882 at col. 44 at lines 4-25; all citations disclosing methods of forming acetate salts of GLP-2 analogues by “exchang[ing] the counter ion trifluoroacetate with acetate”, wherein the GLP-2 analogue was “passed through a column packed with strong base ion exchange resin on acetate”, and following washing steps, “the eluate is collected and lyophilized”.
25 Roux et al., Elimination and exchange of trifluoroacetate counter-ion from cationic peptides: a critical evaluation of different approaches. J Pept Sci. 2008 Mar;14(3):354-9. doi: 10.1002/psc.951. PMID: 18035848; at title, abs, passim explicitly teaching that TFA detection and removal was routine in the art circa 2007.
26 See, e.g., WO’565 at p. 44 at lines 25-36; see also US’552 at col 42 at lines 4-25; see also US’882 at col. 44 at lines 4-25; all citations disclosing methods of forming acetate salts of GLP-2 analogues by “exchang[ing] the counter ion trifluoroacetate with acetate”, wherein the GLP-2 analogue was “passed through a column packed with strong base ion exchange resin on acetate”, and following washing steps, “the eluate is collected and lyophilized”.
27 Roux et al., Elimination and exchange of trifluoroacetate counter-ion from cationic peptides: a critical evaluation of different approaches. J Pept Sci. 2008 Mar;14(3):354-9. doi: 10.1002/psc.951. PMID: 18035848; at title, abs, passim explicitly teaching that TFA detection and removal was routine in the art circa 2007.
28 See, e.g., WO’565 at 32 at line 15 to page 33 at line 6; see esp. id. at 32 at line 34, noting that trifluoroacetate is not recited or mentioned in the list of components for formulations.
29 Krzywinski et al.,Error bars. Nat Methods 10, 921–922 (2013). https://doi.org/10.1038/nmeth.2659; hereafter “Krzywinski”; cited in previous action.
30 Cumming et al.; Error bars in experimental biology. J Cell Biol. 2007 Apr 9;177(1):7-11. doi: 10.1083/jcb.200611141. PMID: 17420288; PMCID: PMC2064100; hereafter “Cumming”; cited in previous action.
31 Brown, Standard error vs. Standard error of measurement, Shiken: JALT Testing & Evaluation SIG Newsletter, 3(1) April 1999 (p. 20-25); hereafter “Brown”; cited in previous action.
32 STEYX function, MedCalc.org, attached as pdf, 1 page, also available at https://www.medcalc.org/manual/STEYX-function.php (last visited 5/09/2025); hereafter “MedCalc”; cited in previous action.
33 Chapter 12.7 Standard Error of the Estimate, Introduction to Statistics, OpenLibrary, ecamplusontario.pressbooks.pub, 12 pages (Sep. 20, 2022), also available at https://ecampusontario.pressbooks.pub/introstats/chapter/12-7-standard-error-of-the-estimate/ (last visited 5/09/2025); cited in prior action.
34 Cited in previous action.
35 Valéry et al., Self-association process of a peptide in solution: from beta-sheet filaments to large embedded nanotubes. Biophys J. 2004 Apr;86(4):2484-501. doi: 10.1016/S0006-3495(04)74304-0. PMID: 15041685; PMCID: PMC1304096; hereafter “Valery”; cited in previous action.