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 .
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
Response to Arguments
Applicant's arguments filed 7/6/2026, with respect to the claim rejections under 35 U.S.C. 103, have been fully considered but they are not persuasive.
Applicant’s position is that, in regards to the rejections based on Larsen in view of Norton, 1) the skilled person would have no reasonable way of predicting whether the formulation would suffer from reduced chemical and/or physical stability when the instantly claimed components are mixed, 2) the cited references do not provide guidance on the stability of CPD1OH formulations that include preservatives in a phosphate buffer, and 3) the instant application demonstrates that CPD1OH formulated with a preservative in phosphate buffer remains stable. Further, 4) Dimarchi teaches broad ranges of components in unbounded lists and does not exemplify any of these in combination with any peptide resembling the CPD10H of the present claims; 5) Xiong does not remedy the deficiencies of Larsen and Norton because it teaches different peptides than those claimed and further recognizes the unpredictable nature of the combination of specific compounds with preservatives in a given buffer; and 6) Quay, Carrington, Parshad, and Carrier each does not remedy the deficiencies of Larsen and Norton because each teaches different peptides than those claimed.
Regarding 1), MPEP 2143.02(II), states “Obviousness does not require absolute predictability, but at least some degree of predictability is required. Evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness. In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976).”. The instant claims are drawn to compositions comprising a peptide known in the art, CPD1OH, as well as preservatives and buffers that are commonly used in the art to formulate different compositions. It is obvious to combine a known peptide with a known preservative and a known buffer to arrive at the instant formulation; such activities would be within the scope of one of ordinary skill in the art and would be reasonably predictable.
Regarding 2), in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, the deficiencies of Larsen are remedied by the teachings of Norton; simply because Norton does not teach exactly the same types of peptides does not negate its teachings. Per MPEP 2123(I), "The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983).”. Consequently, the references in combination render the instant claims obvious.
Regarding 3), MPEP 716.02(b)(I) states that the burden is on the Applicant to establish that the results are unexpected and significant: “The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992).” In the instant application, Tables 5-10, and particularly 7-9, are cited in Applicant’s arguments to indicate unexpected results; however, these Tables do not demonstrate any statistical significance. Thus, this requirement has not been met, and the obviousness rejections have been maintained/modified herein.
Regarding 4) and 6), see 2) above.
Regarding 5), see 1) and 2) above.
Applicant’s arguments filed 7/6/2026, with respect to the double patenting rejections, have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of the amended claims.
Election/Restrictions
Applicant’s election of the species “CPD1OH” in the reply filed on 2/4/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Status
Claims 1-8 and 12-21 are pending. Claims 1, 6, 13, and 19 are currently amended.
Priority
The instant application is the 371 national stage entry of PCT/EP2021/086148, filed 12/16/2021, which claims priority to the foreign application EP20214558.7, filed 12/16/2020. The priority date of 12/16/2020 is acknowledged.
Information Disclosure Statement
The IDS’s submitted on 6/18/2026 and 7/6/2026 are under consideration. Any strikethrough is owed to a lack of a copy of the reference in the file wrapper or illegibility of the reference document.
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.
Claim(s) 1-8 and 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Larsen (WO 2018/104561 A1, published 6/14/2018, cited on IDS filed 6/13/2023) in view of Norton (WO 2020086741 A1, published 4/30/2020) and Dimarchi (AU 2012273364 A1, published 1/16/2014).
Larsen teaches the GLP-1/GLP-2 receptor agonist CPD1OH (Table 1, Pg 69, compound 18), which is identical to the elected species CPD1OH of claim 1.
Larsen does not teach a composition with said dual agonist CPD1OH with one or more of benzoate, benzalkonium chloride and/or benzyl alcohol and phosphate buffer, wherein the phosphate buffer is present at a concentration of from about 5-40mM.
Norton teaches GLP-2 fusion proteins, methods of treatment, and compositions thereof (Abstract). Norton teaches that such pharmaceutical compositions that can include preservatives such as benzoate, benzalkonium chloride and/or benzyl alcohol ([00130, 00138]) and buffers such as phosphate buffer ([00133]).
Dimarchi teaches GLP-1 peptide variants, methods of treatment, and compositions thereof (Abstract). Dimarchi teaches formulations of said compositions wherein a buffer such as phosphate buffer can have a strength (concentration) of at least 5mM to at least 50mM ([00226]).
In summary, Larsen teaches a dual peptide agonist of GLP-1/GLP-2 consisting of the elected species CPD1OH; Norton teaches preservatives and buffers that can be used to make compositions of GLP-2 proteins; and Dimarchi teaches compositions comprising GLP-1 peptides and specific concentrations of phosphate buffer.
Therefore, with regards to claim 1, it would be prima facie obvious to use the preservatives and buffer taught by Norton and Dimarchi to formulate a composition of CPD1OH. One skilled in the art would be motivated to do so and have a reasonable expectation of success because Norton and Dimarchi established that such preservatives and buffers could be used for similar GLP-1 and GLP-2 peptides.
Regarding claim 2, Norton teaches intravenous administration of a composition is a solution in sterile isotonic aqueous buffer ([00136]).
Regarding claim 3, Norton teaches the preservative benzoate ([00130]).
Regarding claim 4, Norton teaches the preservative benzalkonium chloride ([00138]).
Regarding claim 5, Norton teaches the preservative benzyl alcohol ([00130]).
Regarding claim 6, as stated above, Dimarchi teaches pharmaceutical formulations comprising phosphate buffer with a strength (concentration) of at least 5mM to at least 50mM ([00226]).
Regarding claim 7, Dimarchi teaches the buffer can be sodium phosphate ([00224]).
Regarding claim 8, Dimarchi teaches the pH of composition may be at least 6-9 ([00226]).
Regarding claims 12 and 13, Larsen teaches a composition wherein the concentration of the GLP-1/GLP-2 dual agonist is 2mg/mL (Pg 77, Example 3, first line).
Regarding claims 14 and 15, Norton teaches including isotonicity makers, such as sodium chloride, in the pharmaceutical composition ([00130]).
Claim(s) 1-8, 12-16 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Larsen (WO 2018/104561 A1, published 6/14/2018, cited on IDS filed 6/13/2023), Norton (WO 2020086741 A1, published 4/30/2020) and Dimarchi (AU 2012273364 A1, published 1/16/2014), as applied to claims 1-8 and 12-15, and further in view of Xiong et al. (CN 103405753 A, published 11/27/2013).
The teachings of Larsen, Norton, and Dimarchi have been set forth above. Larsen, Norton, and Dimarchi do not teach specific concentrations of benzoate or benzyl alcohol.
Xiong teaches pharmaceutical compositions comprising an insulinotropic peptide, isotonic agent, preservative, solvent, and buffer salt solution, wherein the insulinotropic peptide is GLP-1 or derivatives thereof (Abstract). Xiong teaches including hydroxyl butyl benzoate and/or benzyl alcohol at a concentration of 1-20mg/mL (Equivalent Abstract).
In summary, Larsen, Norton, and Dimarchi teach a composition comprising the instantly claimed peptide CPD1OH, one or more preservatives selected from benzoate, benzalkonium chloride and/or benzyl alcohol, and phosphate buffer at a concentration of 5-40mM. Xiong teaches compositions comprising GLP-1 peptides and specific concentrations of the preservatives benzoate and/or benzyl alcohol. Therefore, regarding claims 16 and 18, it would be prima facie obvious to use the concentrations taught by Xiong to make a composition of the GLP-1/GLP-2 peptide taught by Larsen, Norton, and Dimarchi. One skilled in the art would be motivated to do so and have a reasonable expectation of success because Xiong established that such concentrations could be used for similar GLP-1 peptides.
Claim(s) 1-8, 12-15, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Larsen (WO 2018/104561 A1, published 6/14/2018, cited on IDS filed 6/13/2023), Norton (WO 2020086741 A1, published 4/30/2020) and Dimarchi (AU 2012273364 A1, published 1/16/2014), as applied to claims 1-8 and 12-15, and further in view of Quay et al. (US 20060210614 A1, published 9/21/2006).
The teachings of Larsen, Norton, and Dimarchi have been set forth above Larsen, Norton, and Dimarchi do not teach a specific concentration of benzalkonium chloride.
Quay teaches methods for treating metabolic diseases via intranasal delivery of an exenatide or GLP-1, comprising an aqueous mixture a delivery enhancer, and the pharmaceutical formulations used therein (Abstract; [0020]). Quay teaches including benzalkonium chloride at a concentration of 0-9mg/mL (Table 1, Pg 30).
In summary, Larsen, Norton, and Dimarchi teach a composition comprising the instantly claimed peptide CPD1OH, one or more preservatives selected from benzoate, benzalkonium chloride and/or benzyl alcohol, and phosphate buffer at a concentration of 5-40mM. Quay teaches compositions comprising GLP-1 peptides and specific concentrations of benzalkonium chloride. Therefore, regarding claim 17, it would be prima facie obvious to use the concentration taught by Quay to make a composition of the GLP-1/GLP-2 peptide taught by Larsen, Norton, and Dimarchi. One skilled in the art would be motivated to do so and have a reasonable expectation of success because Quay established that such concentrations could be used for similar GLP-1 peptides.
Claim(s) 1-8, 12-15, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Larsen (WO 2018/104561 A1, published 6/14/2018, cited on IDS filed 6/13/2023), Norton (WO 2020086741 A1, published 4/30/2020) and Dimarchi (AU 2012273364 A1, published 1/16/2014), as applied to claims 1-8 and 12-15, and further in view of Carrington (CN 107108715 A, published 8/29/2017).
The teachings of Larsen, Norton, and Dimarchi have been set forth above. Larsen, Norton, and Dimarchi do not teach that the CPD1OH peptide is a chlorine salt.
Carrington teaches glucagon peptide analogues with agonist activity towards GLP-1 receptor and glucagon receptor (Abstract). Carrington teaches pharmaceutically acceptable salts of the peptides include chlorine salts (Translation Pg 14, first paragraph).
In summary, Larsen, Norton, and Dimarchi teach a composition comprising the instantly claimed peptide CPD1OH, one or more preservatives selected from benzoate, benzalkonium chloride and/or benzyl alcohol, and phosphate buffer at a concentration of 5-40mM. Carrington teaches GLP-1 peptides can be formulated a chlorine salts. Therefore, regarding claim 19, it would be prima facie obvious to generate a chlorine salt of the instant GLP-1/GLP-2 peptide taught by Larsen, Norton, and Dimarchi. One skilled in the art would be motivated to do so and have a reasonable expectation of success because Carrington established that such concentrations could be used for similar GLP-1 peptides.
Claim(s) 1-8, 12-15, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Larsen (WO 2018/104561 A1, published 6/14/2018, cited on IDS filed 6/13/2023), Norton (WO 2020086741 A1, published 4/30/2020) and Dimarchi (AU 2012273364 A1, published 1/16/2014), as applied to claims 1-8 and 12-15, and further in view of Parshad (EP 3628682 A1, published 4/1/2020).
The teachings of Larsen, Norton, and Dimarchi have been set forth above. Larsen, Norton, and Dimarchi do not teach the inclusion of D-mannitol in the composition nor a specific concentration of it.
Parshad teaches stable liquid pharmaceutical formulations of GLP-2 analogues (Abstract). Parshad teaches including mannitol at a concentration of 20-360mM ([0059, 0062, 0063]). Parshad teaches that the mannitol is preferably D-mannitol ([0057]).
In summary, Larsen, Norton, and Dimarchi teach a composition comprising the instantly claimed peptide CPD1OH, one or more preservatives selected from benzoate, benzalkonium chloride and/or benzyl alcohol, and phosphate buffer at a concentration of 5-40mM. Parshad teaches compositions comprising GLP-2 peptides and specific concentrations D-mannitol. Therefore, regarding claim 20, it would be prima facie obvious to use the concentration taught by Parshad to make a composition of the GLP-1/GLP-2 peptide taught by Larsen, Norton, and Dimarchi. One skilled in the art would be motivated to do so and have a reasonable expectation of success because Parshad established that such concentrations could be used for similar GLP-1 peptides.
Claim(s) 1-5, 9-15, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Larsen (WO 2018/104561 A1, published 6/14/2018, cited on IDS filed 6/13/2023), Norton (WO 2020086741 A1, published 4/30/2020) and Dimarchi (AU 2012273364 A1, published 1/16/2014), as applied to claims 1-8 and 12-15, and further in view of Carrier (CA 2708762 A1, published 6/18/2009).
The teachings of Larsen, Norton, and Dimarchi have been set forth above Larsen, Norton, and Dimarchi do not teach a specific concentration of NaCl.
Carrier teaches pharmaceutical formulations comprising insulinotropic peptide conjugates, including GLP-1 derivatives, and methods of administration (Abstract; [00381])). Carrier teaches formulations wherein the concentration of NaCl is 100-200 mM sodium chloride ([0011, 0012, 0080]).
In summary, Larsen, Norton, and Dimarchi teach a composition comprising the instantly claimed peptide CPD1OH, one or more preservatives selected from benzoate, benzalkonium chloride and/or benzyl alcohol, and phosphate buffer at a concentration of 5-40mM. Carrier teaches compositions comprising GLP-1 peptides and specific concentrations of NaCl. Therefore, regarding claim 21, it would be prima facie obvious to use the concentration taught by Carrier to make a composition of the GLP-1/GLP-2 peptide taught by Larsen, Norton, and Dimarchi. One skilled in the art would be motivated to do so and have a reasonable expectation of success because Carrier established that such concentrations could be used for similar GLP-1 peptides.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 and 3-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 10,905,745 B2 (‘745) in view of Norton (WO 2020086741 A1, published 4/30/2020) and Dimarchi (AU 2012273364 A1, published 1/16/2014). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 1 of US ‘745 recites a dual agonist represented by the formula R1-X*-R2, wherein R1 is Hydrogen (Hy), C1-4 alkyl, acetyl, formyl, benzoyl, or trifluoroacetyl; R2 is NH2 or OH; X* is a peptide H[Aib]EGSFTSELATILDψQAARDFIAWLIQHKITD, Ψ is an L or D Lys residue whose side chain is conjugated to a substituent of formula Z1-Z2 and Z1-Z2 is [17-carboxy-heptadecanoyl]-isoGlu-, or a pharmaceutically acceptable salt thereof, which reads on the instant peptide CPD1OH.
Dependent claims include additional variants of the peptide (claims 2 and 3) and pharmaceutical compositions comprising thereof (claims 4 and 5).
US ‘745 does not teach specifically adding one or more preservatives selected from benzoate, benzalkonium chloride, and/or benzyl alcohol, nor does it teach that the composition comprises phosphate buffer in a concentration of 5-40mM.
Norton teaches that pharmaceutical composition comprising GLP-2 fusion proteins can include preservatives such as benzoate, benzalkonium chloride and/or benzyl alcohol ([00130, 00138]) and buffers such as phosphate buffer ([00133]). Dimarchi teaches formulations of GLP-1 peptide compositions wherein a buffer such as phosphate buffer can have a strength (concentration) of at least 5mM to at least 50mM ([00226]). Therefore, it would be prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Norton and Dimarchi into US ‘745, thereby arriving at the instant invention. One skilled in the art would have a reasonable expectation of success as Norton and Dimarchi teach such preservatives and buffer can be used for similar GLP-1 and GLP-2 peptide compositions. Thus, the claims are obvious in view of US ‘745.
Claims 1 and 3-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-6, 10-12, 17-19, 21, 23-24, 27, 28, and 38-45 of U.S. Patent No. 11,395,847 B2 (‘847) in view of Norton (WO 2020086741 A1, published 4/30/2020) and Dimarchi (AU 2012273364 A1, published 1/16/2014). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 1 of US ‘ 847 recites a glucagon-like-peptide 1/glucagon-like-peptide 2 (GLP-1/GLP-2) dual agonist represented by the formula: R1—X*—U—R2, wherein: R1 is hydrogen (Hy), C1-4 alkyl, acetyl, formyl, benzoyl or trifluoroacetyl; R2 is NH2 or OH; X* is a peptide of formula I: (I) (SEQ ID NO: 3) H-X2-EG-X5-F-X7-X8-E-X10-X11-TIL-X15-X16-X17-A- X19-X20-X21-FI-X24-WL-X27-X28-X29-KIT-X33,
wherein: X2 is Aib or G; X5 is T or S; X7 is T or S; X8 is S, E or D; X10 is L, M, V or Ψ; X11 is A, N or S; X15 is D or E; X16 is G, E, A or Ψ; X17 is Q, E, K, L or Ψ; X19 is A, V or S; X20 is R, K or Ψ; X21 is D, L or E; X24 is A, N or S; X27 is I, Q, K, H or Y; X28 is Q, E, A, H, Y, L, K, R or S; X29 is H, Y or Q; X33 is D or E;
U is absent or a sequence of 1-15 residues, each, independently, selected from K, k, E, A, T, I, L and Ψ; the molecule contains one and only one Ψ, wherein Ψ is a residue of K, k, R, Orn, Dap or Dab in which the side chain is conjugated to a substituent having the formula Z1— or Z1—Z2—, wherein Z1— is CH3—(CH2)10-22—(CO)— or HOOC—(CH2)10-22—(CO)—; and
—Z2— is selected from —ZS1—, —ZS1—ZS2—, —ZS2—ZS1—, —ZS2—, —ZS3—, —ZS1—ZS3—, —ZS2—ZS3—, —ZS3—ZS1—, —ZS3—ZS2—, —ZS1—ZS2—ZS3—, —ZS1—ZS3—ZS2—, —ZS2—ZS1—ZS3—, —ZS2—ZS3—ZS1—, —ZS3—ZS1—ZS2—, —ZS3—ZS2—ZS1—, or —ZS2—ZS3—ZS2; wherein
ZS1 is isoGlu, β-Ala, isoLys, or 4-aminobutanoyl; ZS2 is -(Peg3)m-, wherein m is 1, 2, or 3; and
ZS3 is a peptide sequence of 1-6 amino acid residues independently selected from the group consisting of A, L, S, T, Y, Q, D, E, K, k, R, H, F and G; and wherein at least one of X5 and X7 is T; or a pharmaceutically acceptable salt thereof. Wherein R1 is Hy, R2 is OH, X2 is Abi, X5 is S, X7 is T, X8 is S, X10 is L, X11 is A, X15 is D, X16 is Ψ, X17 is Q, X19 is A, X20 is R, X21 is D, X24 is A, X27 is I, X28 is Q, X29 is H, and X33 is D, Ψ is HOOC—(CH2)16—(CO)—isoGlu, and U is absent reads on the instant peptide CPD1OH.
Dependent claims include additional species of the peptide (claims 2, 4-6, 10-12, 17-19, 21, 23-24, 27, 28, 38-42), a pharmaceutical composition thereof (claim 43), and methods of treating (claims 44 and 45); the instant specification indicates that the instant peptides can be used to treat weight gain and obesity (see instant Pg 32, embodiment 30).
US ‘847 does not teach specifically adding one or more preservatives selected from benzoate, benzalkonium chloride, and/or benzyl alcohol, nor does it teach that the composition comprises phosphate buffer in a concentration of 5-40mM.
Norton teaches that pharmaceutical composition comprising GLP-2 fusion proteins can include preservatives such as benzoate, benzalkonium chloride and/or benzyl alcohol ([00130, 00138]) and buffers such as phosphate buffer ([00133]). Dimarchi teaches formulations of GLP-1 peptide compositions wherein a buffer such as phosphate buffer can have a strength (concentration) of at least 5mM to at least 50mM ([00226]). Therefore, it would be prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Norton and Dimarchi into US ‘847, thereby arriving at the instant invention. One skilled in the art would have a reasonable expectation of success as Norton and Dimarchi teach such preservatives and buffer can be used for similar GLP-1 and GLP-2 peptide compositions. Thus, the claims are obvious in view of US ‘847.
Claims 1-8, 12, 14-15, and 19-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-12, and 17-25 of U.S. Patent No. 12,576,025 B2 (‘025) in view of Norton (WO 2020086741 A1, published 4/30/2020). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 1 of US ‘ 025 recites an isotonic parenteral pharmaceutical composition, comprising: a. at least about 1 mg/mL of one or more GLP-1/GLP-2 dual agonist, wherein the one or more GLP-1/GLP-2 dual agonist is Hy-H[Aib]EGSFTSELATILD[K([17-carboxy-heptadecanoyl]-isoGlu)QAARDFIAWLIQHKITD-OH (CPD10H) (SEQ ID NO: 1) or any pharmaceutically acceptable salt thereof b. about 5 mM to about 50 mM of phosphate buffer component; and c. about 190 mM to about 240 mM of one or more tonicity agent, wherein said one or more tonicity agent comprises or consists of mannitol, wherein said composition further comprises a solvent, and wherein said composition has a pH of about pH 6.0 to about pH 8.2. SEQ ID NO: 1 is identical to the instant peptide CPD1OH.
Dependent claims include species and concentrations of the compositions components (claims 2-4 and 6-12) and methods of treating (claims 17-25); the instant specification indicates that the instant peptides can be used to treat weight gain and obesity (see instant Pg 32, embodiment 30).
US ‘025 does not teach specifically adding one or more preservatives selected from benzoate, benzalkonium chloride, and/or benzyl alcohol.
Norton teaches that pharmaceutical composition comprising GLP-2 fusion proteins can include preservatives such as benzoate, benzalkonium chloride and/or benzyl alcohol ([00130, 00138]). Therefore, it would be prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Norton into US ‘025, thereby arriving at the instant invention. One skilled in the art would have a reasonable expectation of success as Norton teaches such preservatives can be used for similar GLP-2 peptide compositions. Thus, the claims are obvious in view of US ‘025.
Claims 1-8, 12-15, and 19-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 7-9, 11-13, 20, 22, and 37-42 of copending Application No. 19/236,746 (‘746 reference application; claim set filed 8/25/2025) in view of Norton (WO 2020086741 A1, published 4/30/2020). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 1 of copending Application No. ‘746 recites an isotonic parenteral pharmaceutical composition, comprising: a. at least about 1 mg/mL of one or more GLP-1/GLP-2 dual agonist, wherein the one or more GLP-1/GLP-2 dual agonist is Hy-H[Aib]EGSFTSELATILD[K([17-carboxy-heptadecanoyl]-isoGlu)]QAARDFIAWLIQHKITD-OH (CPD1OH) (SEQ ID NO: 1) or a pharmaceutically acceptable salt thereof: b. about 1mM to about 200mM of buffer component; and c. about 1mM to about 500mM of one or more tonicity agent, wherein said one or more tonicity agent comprises a non-ionic tonicity agent, wherein the non-ionic tonicity agent is mannitol, wherein said composition further comprises a solvent, and wherein said composition has a pH of about pH 6.0 to about 8.2. The CPD1OH peptide of copending Application No. ‘746 is identical to the instant peptide CPD1OH.
Dependent claims include species and concentrations of the compositions components (claims 2, 7-9, 11-13, 20, 22, and 38-42; phosphate buffer is specifically recited in claim 7) and methods of treating (claim 37); the instant specification indicates that the instant peptides can be used to treat weight gain and obesity (see instant Pg 32, embodiment 30).
Copending Application No. ‘746 does not teach specifically adding one or more preservatives selected from benzoate, benzalkonium chloride, and/or benzyl alcohol.
Norton teaches that pharmaceutical composition comprising GLP-2 fusion proteins can include preservatives such as benzoate, benzalkonium chloride and/or benzyl alcohol ([00130, 00138]). Therefore, it would be prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Norton into copending Application No. ‘746, thereby arriving at the instant invention. One skilled in the art would have a reasonable expectation of success as Norton teaches such preservatives can be used for similar GLP-2 peptide compositions. Thus, the claims are obvious in view of copending Application No. ‘746.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-8 and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 11-13, 15, 16, 19, 20, and 24-32 of copending Application No. 17/834,062 (‘062 reference application; claim set filed 5/14/2026) in view of Norton (WO 2020086741 A1, published 4/30/2020) and Dimarchi (AU 2012273364 A1, published 1/16/2014). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 1 of copending Application No. ‘062 recites a method of prophylaxis or treatment of (a) malabsorption, ulcers, short-bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, irritable bowel syndrome, pouchitis, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, mucositis induced by chemotherapy or radiation therapy, diarrhea induced by chemotherapy or radiation therapy, low grade inflammation, metabolic endotoxemia, necrotising enterocolitis, primary biliary cirrhosis, hepatitis, fatty liver disease, or gastrointestinal side-effects of inflammatory conditions in a subject in need thereof, or (b) obesity, morbid obesity, obesity-linked gallbladder disease, obesity-induced sleep apnea, inadequate glucose control, glucose tolerance, dyslipidaemia, diabetes, pre-diabetes, metabolic syndrome or hypertension in a subject in need thereof; the method comprising administering a glucagon-like-peptide 1/glucagon-like peptide 2 (GLP-1/GLP-2) dual agonist, or pharmaceutically acceptable salt thereof, to the subject, wherein the GLP-1/GLP-2 dual agonist is represented by the formula: R1—X*—U—R2, wherein: R1 is hydrogen (Hy), C1-4 alkyl, acetyl, formyl, benzoyl or trifluoroacetyl; R2 is NH2 or OH; X* is a peptide of formula I: (I) (SEQ ID NO: 3) H-X2-EG-X5-F-X7-X8-E-X10-X11-TIL-X15-X16-X17-A- X19-X20-X21-FI-X24-WL-X27-X28-X29-KIT-X33,
wherein: X2 is Aib or G; X5 is T or S; X7 is T or S; X8 is S, E or D; X10 is L, M, V or Ψ; X11 is A, N or S; X15 is D or E; X16 is G, E, A or Ψ; X17 is Q, E, K, L or Ψ; X19 is A, V or S; X20 is R, K or Ψ; X21 is D, L or E; X24 is A, N or S; X27 is I, Q, K, H or Y; X28 is Q, E, A, H, Y, L, K, R or S; X29 is H, Y or Q; X33 is D or E;
U is absent or a sequence of 1-15 residues, each, independently, selected from K, k, E, A, T, I, L and Ψ; the molecule contains one and only one Ψ, wherein Ψ is a residue of K, k, R, Orn, Dap or Dab in which the side chain is conjugated to a substituent having the formula Z1— or Z1—Z2—, wherein Z1— is CH3—(CH2)10-22—(CO)— or HOOC—(CH2)10-22—(CO)—; and
—Z2— is selected from —ZS1—, —ZS1—ZS2—, —ZS2—ZS1—, —ZS2—, —ZS3—, —ZS1—ZS3—, —ZS2—ZS3—, —ZS3—ZS1—, —ZS3—ZS2—, —ZS1—ZS2—ZS3—, —ZS1—ZS3—ZS2—, —ZS2—ZS1—ZS3—, —ZS2—ZS3—ZS1—, —ZS3—ZS1—ZS2—, —ZS3—ZS2—ZS1—, or —ZS2—ZS3—ZS2; wherein
ZS1 is isoGlu, β-Ala, isoLys, or 4-aminobutanoyl; ZS2 is -(Peg3)m-, wherein m is 1, 2, or 3; and
ZS3 is a peptide sequence of 1-6 amino acid residues independently selected from the group consisting of A, L, S, T, Y, Q, D, E, K, k, R, H, F and G; and wherein at least one of X5 and X7 is T; or a pharmaceutically acceptable salt thereof. Wherein R1 is Hy, R2 is OH, X2 is Abi, X5 is S, X7 is T, X8 is S, X10 is L, X11 is A, X15 is D, X16 is Ψ, X17 is Q, X19 is A, X20 is R, X21 is D, X24 is A, X27 is I, X28 is Q, X29 is H and X33 is D, Ψ is HOOC—(CH2)16—(CO)—isoGlu, and U is absent reads on the instant peptide CPD1OH. Further, the instant specification teaches that the instant peptides can be used to treat (a) and (b) as described above (see instant Pg 32, embodiment 30). The methods of claims 2 are also taught in the instant specification (Pg 22, “Indications,” second paragraph).
Dependent claims include species of the peptide (claims 3-7, 11-13, 15, 16, 19, 20, 24-29) and additional methods of treating (claims 2 and 30-32).
Copending Application No. ‘062 does not teach specifically adding one or more preservatives selected from benzoate, benzalkonium chloride, and/or benzyl alcohol, nor does it teach that the composition comprises phosphate buffer.
Norton teaches that pharmaceutical composition comprising GLP-2 fusion proteins can include preservatives such as benzoate, benzalkonium chloride and/or benzyl alcohol ([00130, 00138]) and buffers such as phosphate buffer ([00133]). Dimarchi teaches formulations of GLP-1 peptide compositions wherein a buffer such as phosphate buffer can have a strength (concentration) of at least 5mM to at least 50mM ([00226]). Therefore, it would be prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Norton and Dimarchi into copending Application No. ‘062, thereby arriving at the instant invention. One skilled in the art would have a reasonable expectation of success as Norton and Dimarchi teach such preservatives and buffer can be used for similar GLP-1 and GLP-2 peptide compositions. Thus, the claims are obvious in view of copending Application No. ‘062.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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