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 . 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.
Election/Restrictions
Applicants elected formulation C of table 7 in the disclosure without traverse in the reply filed on 23 July, 2024.
Claims Status
Claims 27-36 and 41-53 are pending.
Claims 27-29, 34, 35, and 41-51 have been amended.
Claims 52 and 53 are new.
Claims 31-33, 42-51, and 53 have been withdrawn from consideration due to an election/restriction requirement.
Withdrawn Rejections
The rejection of claim(s) 27-30, 34-36, and 41 under 35 U.S.C. 103 as being unpatentable over Smith et al (Pharm. Therapeut. (2016) 41(6) p357-360) in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096) is hereby withdrawn due to amendment.
The rejection of claims 27-30, 34-36, and 41 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-5 of U.S. Patent No. 12,059,452 in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096) is hereby withdrawn due to amendment.
The provisional rejection of claims 27-30, 34-36, and 41 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/795,797 (US 20230088005) in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096) is hereby withdrawn due to amendment.
The provisional rejection of claims 27-30, 34-36, and 41 on the ground of nonstatutory double patenting as being unpatentable over claims 37 and 38 of copending Application No. 17/720,993 (US 20220251172) in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096) is hereby withdrawn due to amendment.
The rejection of claims 27-30, 34-36, and 41 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,890,325 in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096) is hereby withdrawn due to amendment.
The provisional rejection of claims 27-30, 34-36, and 41 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/409,277 (US 20240139287) in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096 is hereby withdrawn due to amendment.
The rejection of claims 27-30, 34-36, and 41 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,576,950 in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096) is hereby withdrawn due to amendment.
The provisional rejection of claims 27-30, 34-36, and 41 on the ground of nonstatutory double patenting as being unpatentable over claim 36 of copending Application No. 18/149,982 (US 20240189394) in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096) is hereby withdrawn due to amendment.
The provisional rejection of claims 27-30, 34-36, and 41 on the ground of nonstatutory double patenting as being unpatentable over claim 42 of copending Application No. 18/523,645 (US 20240197835) in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096) is hereby withdrawn due to amendment.
The rejection of claims 27-30, 34-36, and 41 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-5 of U.S. Patent No. 9,884,093 in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096) is hereby withdrawn due to amendment.
The rejection of claims 27-30, 34-36, and 41 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11,253,574 in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096) is hereby withdrawn due to amendment.
The rejection of claims 27-30, 34-36, and 41 on the ground of nonstatutory double patenting as being unpatentable over claims 17-21-5 of US Patent No 12,059,452 in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096) is hereby withdrawn due to amendment.
The rejection of claims 27-30, 34-36, and 41 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of U.S. Patent No. 9,161,953 in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096) is hereby withdrawn due to amendment.
The rejection of claims 27-30, 34-36, and 41 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 7,452,966 in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096) is hereby withdrawn due to amendment.
The rejection of claims 27-30, 34-36, and 41 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 8,273,854 in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096) is hereby withdrawn due to amendment.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 27-30, 34-36, 41, and 52 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 27 and claims dependent on it has a requirement that the formulation be clear. Applicants have defined clear as transparent, does not have a cloudy or milky appearance, and does not contain visibly detectable solid particles of material (p10, 3d paragraph). Wang et al (https://www.biorxiv.org/content/10.1101/348904v1.full.pdf (2018)) states that turbidity (i.e. cloudiness) scales linearly with the path length (4th page, 3d paragraph). This means a solution that appears clear in a 50 micron capillary may appear cloudy in a 1000L reaction vessel. Nor have applicants defined a cutoff between a clear and a not clear solution.
response to applicant’s arguments
Applicants argue that the claim is not being interpreted as a whole, and that a person of skill in the art would understand what “clear” means.
Applicant's arguments filed 16 Oct, 2025 have been fully considered but they are not persuasive.
The interpretation of a claim term is based on the definition given by applicants in their disclosure. If there is no definition given, it is interpreted as it would be read by a person of ordinary skill in the art (MPEP 2111.01(I)). Applicants have given a definition, as noted in the rejection. However, the definition gives no cutoffs between clear and not clear, and does not define the test used to determine clarity; both issues that could change if a given embodiment is clear or not clear.
Applicants argue that the claim language is not being interpreted as a whole. The claim language is interpreted as applicants have defined the term. Applicants have pointed to no part of the claim or disclosure that would change the interpretation.
Applicants argue that a person of skill in the art knows what clear means. However, applicant’s definition governs the interpretation of claim language, and that definition is indefinite.
New Rejections
Claim Rejections - 35 USC § 103
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) 27-30, 34-36, 41, and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Matfin et al (J. Diabetes Sci. Technol. (2015) 9(5) p1071-1079) in view of Zapadka et al (Interface. Focus (2017) 7:20170030) and Vagenende et al (Biochemistry (2009) 48 p11084-11096).
Applicants are claiming a formulation with dulaglutide, polysorbate 80, a phenolic preservative selected from a Markush group comprising phenol, and a solvent modifier selected from a Markush group including glycerol.
Matfin et al discuss once weekly dulaglutide single dose pen usage (title). This was a study to see if patients could use the single dose pen (interpreted as a vial) to treat type 2 diabetes (p1072, 1st column, 2nd paragraph). It was determined that patients could be used safely and effectively by these patients (p1078, 1st column, 6th paragraph).
The difference between this reference and the examined claims is that this reference does not discuss the formulation used.
Zapadka et al discuss the factors affecting the stability of peptide therapeutics (title). Electrostatic interactions are known to play a role in aggregation (p7, 1st column, 5th paragraph), which is controlled by pH and ionic strength (p7, 2nd column, 1st paragraph). In addition, other decomposition mechanisms are dependent on pH (p8, 1st column, 3d paragraph). This strongly suggests optimizing pH of polypeptide formulations for stability. The most commonly used buffers are acetate, citrate, histidine, phosphate, tris, and glycine (p10, 1st column, 4th paragraph). While they may have some formulation issues, Tween 80 (another name for polysorbate 80) is often used to prevent aggregation and absorption (p10, 1st column, 6th paragraph, continues to 2nd column). Preservatives are often used; the most common ones are m-cresol, phenol, and benzyl alcohol (p10, 2nd column, 5th paragraph). Concentration of the polypeptide also plays an important role in stability, affecting aggregation kinetics (p4, 1st column, 1st paragraph). This reference discusses various components and considerations in polypeptide formulations.
Vagenende et al discuss the mechanisms of protein stabilization by glycerol (title). One of the most widely used polyols to stabilize polypeptides is glycerol, including in biopharmaceuticals (p11084, 2nd column, 2nd paragraph). This excipient reduces polypeptide flexibility, stabilizes partially unfolded intermediates, and reduces aggregation (p11084, 2nd column, 2nd paragraph). This reference discusses glycerol as a polypeptide stabilizer.
Therefore, it would be obvious to optimize the pH of the dulaglutide formulations of Matfin et al, to minimize aggregation and decomposition pathways, as discussed by Zapadka et al. As pH optimization is standard in polypeptide formulations, an artisan in this field would attempt this process with a reasonable expectation of success.
Furthermore, it would be obvious to formulate the material with Tween 80, phenol, a buffer, and glycerol to further stabilize the formulation, as discussed by both Zapadka et al and Vagenende et al. As these materials are commonly used for this purpose, an artisan in this field would add these ingredients with a reasonable expectation of success.
Matfin et al discuss dulaglutide. Zapadka et al and Vagenende et al render obvious formulating it with Tween 80 (another name for polysorbate 80), phenol, and glycerol. Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art, as this is a parameter that is routinely optimized (MPEP2144.05.II). Note that Zapadka et al states that the concentration and the ionic strength (which is dependent on buffer concentration) will both affect stability. Turbidity is particles, that is instability. The point of the optimization is to improve stability, thus, the material would reasonably be expected to be clear. Thus, the combination of references renders obvious claims 27-30, 34, and 35
Thus, the combination of references renders obvious claims 28-30, and 35.
Zapadka et al list a small number of buffers that are commonly used, including citrate. Should the optimum pH be appropriate for this buffer, it is thus obvious, rendering obvious claims 36 and 41.
Matfin et al discusses an autoinjector, which reads on a vial (a small closed or closable vessel especially for liquids, Merriam Webster online dictionary), rendering obvious claim 52.
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.
first rejection
Claims 27-30, 34-36, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-5 of U.S. Patent No. 12,059,452 in view of Zapadka et al (Interface. Focus (2017) 7:20170030), Vagenende et al (Biochemistry (2009) 48 p11084-11096), and Matfin et al (J. Diabetes Sci. Technol. (2015) 9(5) p1071-1079).
Competing claim 1 describes a fusion protein composition, while competing claims 3-5 specify an additional pharmaceutical agent, specifically dulaglutide.
The difference between the competing claims and the examined claims is that the competing claims do not specify the formulation.
Zapadka et al discuss the factors affecting the stability of peptide therapeutics (title). Electrostatic interactions are known to play a role in aggregation (p7, 1st column, 5th paragraph), which is controlled by pH and ionic strength (p7, 2nd column, 1st paragraph). In addition, other decomposition mechanisms are dependent on pH (p8, 1st column, 3d paragraph). This strongly suggests optimizing pH of polypeptide formulations for stability. The most commonly used buffers are acetate, citrate, histidine, phosphate, tris, and glycine (p10, 1st column, 4th paragraph). While they may have some formulation issues, Tween 80 (another name for polysorbate 80) is often used to prevent aggregation and absorption (p10, 1st column, 6th paragraph, continues to 2nd column). Preservatives are often used; the most common ones are m-cresol, phenol, and benzyl alcohol (p10, 2nd column, 5th paragraph). Concentration of the polypeptide also plays an important role in stability, affecting aggregation kinetics (p4, 1st column, 1st paragraph). This reference discusses various components and considerations in polypeptide formulations.
Vagenende et al discuss the mechanisms of protein stabilization by glycerol (title). One of the most widely used polyols to stabilize proteins is glycerol, including in biopharmaceuticals (p11084, 2nd column, 2nd paragraph). This excipient reduces polypeptide flexibility, stabilizes partially unfolded intermediates, and reduces aggregation (p11084, 2nd column, 2nd paragraph). This reference discusses glycerol as a polypeptide stabilizer.
Matfin et al discuss once weekly dulaglutide single dose pen usage (title). This was a study to see if patients could use the single dose pen (interpreted as a vial) to treat type 2 diabetes (p1072, 1st column, 2nd paragraph). It was determined that patients could be used safely and effectively by these patients (p1078, 1st column, 6th paragraph). Pens are shown to be easier to use than syringes, which is suggested leads to improved adherence and glycemic control (p1078, 1st column, 4th paragraph). This reference discusses using pens to administer the drug.
Therefore, it would be obvious to optimize the pH of the dulaglutide formulations of the competing claims, to reduce aggregation and decomposition pathways, as discussed by Zapadka et al. As pH optimization is standard in polypeptide formulations, an artisan in this field would attempt this process with a reasonable expectation of success.
Furthermore, it would be obvious to formulate the material with Tween 80, phenol, a buffer, and glycerol to further stabilize the formulation, as discussed by both Zapadka et al and Vagenende et al. As these materials are commonly used for this purpose, an artisan in this field would add these ingredients with a reasonable expectation of success.
Finally, it would be obvious to use the pen system of Matfin et al, as an easy way of self-administering the material. As Matfin et al states that such systems work well in other studies, an artisan in this field would attempt this device with a reasonable expectation of success.
second rejection
Claims 27-30, 34-36, and 41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/795,797 (US 20230088005) in view of Zapadka et al (Interface. Focus (2017) 7:20170030), Vagenende et al (Biochemistry (2009) 48 p11084-11096), and Matfin et al (J. Diabetes Sci. Technol. (2015) 9(5) p1071-1079)
Competing claim 1 describes a method of treating, preventing, or delaying development of a cognitive disorder in a patient, comprising administering dulaglutide.
The difference between the competing claim and the examined claims is that the competing claims do not specify the formulation.
Zapadka et al discuss the factors affecting the stability of peptide therapeutics (title). Electrostatic interactions are known to play a role in aggregation (p7, 1st column, 5th paragraph), which is controlled by pH and ionic strength (p7, 2nd column, 1st paragraph). In addition, other decomposition mechanisms are dependent on pH (p8, 1st column, 3d paragraph). This strongly suggests optimizing pH of polypeptide formulations for stability. The most commonly used buffers are acetate, citrate, histidine, phosphate, tris, and glycine (p10, 1st column, 4th paragraph). While they may have some formulation issues, Tween 80 (another name for polysorbate 80) is often used to prevent aggregation and absorption (p10, 1st column, 6th paragraph, continues to 2nd column). Preservatives are often used; the most common ones are m-cresol, phenol, and benzyl alcohol (p10, 2nd column, 5th paragraph). Concentration of the polypeptide also plays an important role in stability, affecting aggregation kinetics (p4, 1st column, 1st paragraph). This reference discusses various components and considerations in polypeptide formulations.
Vagenende et al discuss the mechanisms of protein stabilization by glycerol (title). One of the most widely used polyols to stabilize proteins is glycerol, including in biopharmaceuticals (p11084, 2nd column, 2nd paragraph). This excipient reduces polypeptide flexibility, stabilizes partially unfolded intermediates, and reduces aggregation (p11084, 2nd column, 2nd paragraph). This reference discusses glycerol as a polypeptide stabilizer.
Matfin et al discuss once weekly dulaglutide single dose pen usage (title). This was a study to see if patients could use the single dose pen (interpreted as a vial) to treat type 2 diabetes (p1072, 1st column, 2nd paragraph). It was determined that patients could be used safely and effectively by these patients (p1078, 1st column, 6th paragraph). Pens are shown to be easier to use than syringes, which is suggested leads to improved adherence and glycemic control (p1078, 1st column, 4th paragraph). This reference discusses using pens to administer the drug.
Therefore, it would be obvious to optimize the pH of the dulaglutide formulations of the competing claims, to reduce aggregation and decomposition pathways, as discussed by Zapadka et al. As pH optimization is standard in polypeptide formulations, an artisan in this field would attempt this process with a reasonable expectation of success.
Furthermore, it would be obvious to formulate the material with Tween 80, phenol, a buffer, and glycerol to further stabilize the formulation, as discussed by both Zapadka et al and Vagenende et al. As these materials are commonly used for this purpose, an artisan in this field would add these ingredients with a reasonable expectation of success.
Finally, it would be obvious to use the pen system of Matfin et al, as an easy way of self-administering the material. As Matfin et al states that such systems work well in other studies, an artisan in this field would attempt this device with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
third rejection
Claims 27-30, 34-36, and 41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 37 and 38 of copending Application No. 17/720,993 (US 20220251172) in view of Zapadka et al (Interface. Focus (2017) 7:20170030), Vagenende et al (Biochemistry (2009) 48 p11084-11096), and Matfin et al (J. Diabetes Sci. Technol. (2015) 9(5) p1071-1079).
Competing claims 37 and 38 describe a pharmaceutical composition with some product by process limitations, containing a therapeutic selected from a Markush group including dulaglutide.
The difference between the competing claims and the examined claims is that the competing claims do not specify the formulation.
Zapadka et al discuss the factors affecting the stability of peptide therapeutics (title). Electrostatic interactions are known to play a role in aggregation (p7, 1st column, 5th paragraph), which is controlled by pH and ionic strength (p7, 2nd column, 1st paragraph). In addition, other decomposition mechanisms are dependent on pH (p8, 1st column, 3d paragraph). This strongly suggests optimizing pH of polypeptide formulations for stability. The most commonly used buffers are acetate, citrate, histidine, phosphate, tris, and glycine (p10, 1st column, 4th paragraph). While they may have some formulation issues, Tween 80 (another name for polysorbate 80) is often used to prevent aggregation and absorption (p10, 1st column, 6th paragraph, continues to 2nd column). Preservatives are often used; the most common ones are m-cresol, phenol, and benzyl alcohol (p10, 2nd column, 5th paragraph). Concentration of the polypeptide also plays an important role in stability, affecting aggregation kinetics (p4, 1st column, 1st paragraph). This reference discusses various components and considerations in polypeptide formulations.
Vagenende et al discuss the mechanisms of protein stabilization by glycerol (title). One of the most widely used polyols to stabilize proteins is glycerol, including in biopharmaceuticals (p11084, 2nd column, 2nd paragraph). This excipient reduces polypeptide flexibility, stabilizes partially unfolded intermediates, and reduces aggregation (p11084, 2nd column, 2nd paragraph). This reference discusses glycerol as a polypeptide stabilizer.
Matfin et al discuss once weekly dulaglutide single dose pen usage (title). This was a study to see if patients could use the single dose pen (interpreted as a vial) to treat type 2 diabetes (p1072, 1st column, 2nd paragraph). It was determined that patients could be used safely and effectively by these patients (p1078, 1st column, 6th paragraph). Pens are shown to be easier to use than syringes, which is suggested leads to improved adherence and glycemic control (p1078, 1st column, 4th paragraph). This reference discusses using pens to administer the drug.
Therefore, it would be obvious to optimize the pH of the dulaglutide formulations of the competing claims, to reduce aggregation and decomposition pathways, as discussed by Zapadka et al. As pH optimization is standard in polypeptide formulations, an artisan in this field would attempt this process with a reasonable expectation of success.
Furthermore, it would be obvious to formulate the material with Tween 80, phenol, a buffer, and glycerol to further stabilize the formulation, as discussed by both Zapadka et al and Vagenende et al. As these materials are commonly used for this purpose, an artisan in this field would add these ingredients with a reasonable expectation of success.
Finally, it would be obvious to use the pen system of Matfin et al, as an easy way of self-administering the material. As Matfin et al states that such systems work well in other studies, an artisan in this field would attempt this device with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
fourth rejection
Claims 27-30, 34-36, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,890,325 in view of Zapadka et al (Interface. Focus (2017) 7:20170030), Vagenende et al (Biochemistry (2009) 48 p11084-11096), and Matfin et al (J. Diabetes Sci. Technol. (2015) 9(5) p1071-1079).
Competing claim 1 describes a therapeutic method using dulaglutide.
The difference between the competing claims and the examined claims is that the competing claims do not specify the formulation.
Zapadka et al discuss the factors affecting the stability of peptide therapeutics (title). Electrostatic interactions are known to play a role in aggregation (p7, 1st column, 5th paragraph), which is controlled by pH and ionic strength (p7, 2nd column, 1st paragraph). In addition, other decomposition mechanisms are dependent on pH (p8, 1st column, 3d paragraph). This strongly suggests optimizing pH of polypeptide formulations for stability. The most commonly used buffers are acetate, citrate, histidine, phosphate, tris, and glycine (p10, 1st column, 4th paragraph). While they may have some formulation issues, Tween 80 (another name for polysorbate 80) is often used to prevent aggregation and absorption (p10, 1st column, 6th paragraph, continues to 2nd column). Preservatives are often used; the most common ones are m-cresol, phenol, and benzyl alcohol (p10, 2nd column, 5th paragraph). Concentration of the polypeptide also plays an important role in stability, affecting aggregation kinetics (p4, 1st column, 1st paragraph). This reference discusses various components and considerations in polypeptide formulations.
Vagenende et al discuss the mechanisms of protein stabilization by glycerol (title). One of the most widely used polyols to stabilize proteins is glycerol, including in biopharmaceuticals (p11084, 2nd column, 2nd paragraph). This excipient reduces polypeptide flexibility, stabilizes partially unfolded intermediates, and reduces aggregation (p11084, 2nd column, 2nd paragraph). This reference discusses glycerol as a polypeptide stabilizer.
Matfin et al discuss once weekly dulaglutide single dose pen usage (title). This was a study to see if patients could use the single dose pen (interpreted as a vial) to treat type 2 diabetes (p1072, 1st column, 2nd paragraph). It was determined that patients could be used safely and effectively by these patients (p1078, 1st column, 6th paragraph). Pens are shown to be easier to use than syringes, which is suggested leads to improved adherence and glycemic control (p1078, 1st column, 4th paragraph). This reference discusses using pens to administer the drug.
Therefore, it would be obvious to optimize the pH of the dulaglutide formulations of the competing claims, to reduce aggregation and decomposition pathways, as discussed by Zapadka et al. As pH optimization is standard in polypeptide formulations, an artisan in this field would attempt this process with a reasonable expectation of success.
Furthermore, it would be obvious to formulate the material with Tween 80, phenol, a buffer, and glycerol to further stabilize the formulation, as discussed by both Zapadka et al and Vagenende et al. As these materials are commonly used for this purpose, an artisan in this field would add these ingredients with a reasonable expectation of success.
Finally, it would be obvious to use the pen system of Matfin et al, as an easy way of self-administering the material. As Matfin et al states that such systems work well in other studies, an artisan in this field would attempt this device with a reasonable expectation of success.
fifth rejection
Claims 27-30, 34-36, and 41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/409,277 (US 20240139287) in view of Zapadka et al (Interface. Focus (2017) 7:20170030), Vagenende et al (Biochemistry (2009) 48 p11084-11096), and Matfin et al (J. Diabetes Sci. Technol. (2015) 9(5) p1071-1079).
Competing claim 1 describes a therapeutic method using dulaglutide.
The difference between the competing claims and the examined claims is that the competing claims do not specify the formulation.
Zapadka et al discuss the factors affecting the stability of peptide therapeutics (title). Electrostatic interactions are known to play a role in aggregation (p7, 1st column, 5th paragraph), which is controlled by pH and ionic strength (p7, 2nd column, 1st paragraph). In addition, other decomposition mechanisms are dependent on pH (p8, 1st column, 3d paragraph). This strongly suggests optimizing pH of polypeptide formulations for stability. The most commonly used buffers are acetate, citrate, histidine, phosphate, tris, and glycine (p10, 1st column, 4th paragraph). While they may have some formulation issues, Tween 80 (another name for polysorbate 80) is often used to prevent aggregation and absorption (p10, 1st column, 6th paragraph, continues to 2nd column). Preservatives are often used; the most common ones are m-cresol, phenol, and benzyl alcohol (p10, 2nd column, 5th paragraph). Concentration of the polypeptide also plays an important role in stability, affecting aggregation kinetics (p4, 1st column, 1st paragraph). This reference discusses various components and considerations in polypeptide formulations.
Vagenende et al discuss the mechanisms of protein stabilization by glycerol (title). One of the most widely used polyols to stabilize proteins is glycerol, including in biopharmaceuticals (p11084, 2nd column, 2nd paragraph). This excipient reduces polypeptide flexibility, stabilizes partially unfolded intermediates, and reduces aggregation (p11084, 2nd column, 2nd paragraph). This reference discusses glycerol as a polypeptide stabilizer.
Matfin et al discuss once weekly dulaglutide single dose pen usage (title). This was a study to see if patients could use the single dose pen (interpreted as a vial) to treat type 2 diabetes (p1072, 1st column, 2nd paragraph). It was determined that patients could be used safely and effectively by these patients (p1078, 1st column, 6th paragraph). Pens are shown to be easier to use than syringes, which is suggested leads to improved adherence and glycemic control (p1078, 1st column, 4th paragraph). This reference discusses using pens to administer the drug.
Therefore, it would be obvious to optimize the pH of the dulaglutide formulations of the competing claims, to reduce aggregation and decomposition pathways, as discussed by Zapadka et al. As pH optimization is standard in polypeptide formulations, an artisan in this field would attempt this process with a reasonable expectation of success.
Furthermore, it would be obvious to formulate the material with Tween 80, phenol, a buffer, and glycerol to further stabilize the formulation, as discussed by both Zapadka et al and Vagenende et al. As these materials are commonly used for this purpose, an artisan in this field would add these ingredients with a reasonable expectation of success.
Finally, it would be obvious to use the pen system of Matfin et al, as an easy way of self-administering the material. As Matfin et al states that such systems work well in other studies, an artisan in this field would attempt this device with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
sixth rejection
Claims 27-30, 34-36, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,576,950 in view of Zapadka et al (Interface. Focus (2017) 7:20170030), Vagenende et al (Biochemistry (2009) 48 p11084-11096). , and Matfin et al (J. Diabetes Sci. Technol. (2015) 9(5) p1071-1079).
Competing claim 1 describes a therapeutic method using dulaglutide.
The difference between the competing claims and the examined claims is that the competing claims do not specify the formulation.
Zapadka et al discuss the factors affecting the stability of peptide therapeutics (title). Electrostatic interactions are known to play a role in aggregation (p7, 1st column, 5th paragraph), which is controlled by pH and ionic strength (p7, 2nd column, 1st paragraph). In addition, other decomposition mechanisms are dependent on pH (p8, 1st column, 3d paragraph). This strongly suggests optimizing pH of polypeptide formulations for stability. The most commonly used buffers are acetate, citrate, histidine, phosphate, tris, and glycine (p10, 1st column, 4th paragraph). While they may have some formulation issues, Tween 80 (another name for polysorbate 80) is often used to prevent aggregation and absorption (p10, 1st column, 6th paragraph, continues to 2nd column). Preservatives are often used; the most common ones are m-cresol, phenol, and benzyl alcohol (p10, 2nd column, 5th paragraph). Concentration of the polypeptide also plays an important role in stability, affecting aggregation kinetics (p4, 1st column, 1st paragraph). This reference discusses various components and considerations in polypeptide formulations.
Vagenende et al discuss the mechanisms of protein stabilization by glycerol (title). One of the most widely used polyols to stabilize proteins is glycerol, including in biopharmaceuticals (p11084, 2nd column, 2nd paragraph). This excipient reduces polypeptide flexibility, stabilizes partially unfolded intermediates, and reduces aggregation (p11084, 2nd column, 2nd paragraph). This reference discusses glycerol as a polypeptide stabilizer.
Matfin et al discuss once weekly dulaglutide single dose pen usage (title). This was a study to see if patients could use the single dose pen (interpreted as a vial) to treat type 2 diabetes (p1072, 1st column, 2nd paragraph). It was determined that patients could be used safely and effectively by these patients (p1078, 1st column, 6th paragraph). Pens are shown to be easier to use than syringes, which is suggested leads to improved adherence and glycemic control (p1078, 1st column, 4th paragraph). This reference discusses using pens to administer the drug.
Therefore, it would be obvious to optimize the pH of the dulaglutide formulations of the competing claims, to reduce aggregation and decomposition pathways, as discussed by Zapadka et al. As pH optimization is standard in polypeptide formulations, an artisan in this field would attempt this process with a reasonable expectation of success.
Furthermore, it would be obvious to formulate the material with Tween 80, phenol, a buffer, and glycerol to further stabilize the formulation, as discussed by both Zapadka et al and Vagenende et al. As these materials are commonly used for this purpose, an artisan in this field would add these ingredients with a reasonable expectation of success.
Finally, it would be obvious to use the pen system of Matfin et al, as an easy way of self-administering the material. As Matfin et al states that such systems work well in other studies, an artisan in this field would attempt this device with a reasonable expectation of success.
seventh rejection
Claims 27-30, 34-36, and 41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 36 of copending Application No. 18/149,982 (US 20240189394) in view of Zapadka et al (Interface. Focus (2017) 7:20170030), Vagenende et al (Biochemistry (2009) 48 p11084-11096), and Matfin et al (J. Diabetes Sci. Technol. (2015) 9(5) p1071-1079).
Competing claim 36 describes a therapeutic method using dulaglutide.
The difference between the competing claims and the examined claims is that the competing claims do not specify the formulation.
Zapadka et al discuss the factors affecting the stability of peptide therapeutics (title). Electrostatic interactions are known to play a role in aggregation (p7, 1st column, 5th paragraph), which is controlled by pH and ionic strength (p7, 2nd column, 1st paragraph). In addition, other decomposition mechanisms are dependent on pH (p8, 1st column, 3d paragraph). This strongly suggests optimizing pH of polypeptide formulations for stability. The most commonly used buffers are acetate, citrate, histidine, phosphate, tris, and glycine (p10, 1st column, 4th paragraph). While they may have some formulation issues, Tween 80 (another name for polysorbate 80) is often used to prevent aggregation and absorption (p10, 1st column, 6th paragraph, continues to 2nd column). Preservatives are often used; the most common ones are m-cresol, phenol, and benzyl alcohol (p10, 2nd column, 5th paragraph). Concentration of the polypeptide also plays an important role in stability, affecting aggregation kinetics (p4, 1st column, 1st paragraph). This reference discusses various components and considerations in polypeptide formulations.
Vagenende et al discuss the mechanisms of protein stabilization by glycerol (title). One of the most widely used polyols to stabilize proteins is glycerol, including in biopharmaceuticals (p11084, 2nd column, 2nd paragraph). This excipient reduces polypeptide flexibility, stabilizes partially unfolded intermediates, and reduces aggregation (p11084, 2nd column, 2nd paragraph). This reference discusses glycerol as a polypeptide stabilizer.
Matfin et al discuss once weekly dulaglutide single dose pen usage (title). This was a study to see if patients could use the single dose pen (interpreted as a vial) to treat type 2 diabetes (p1072, 1st column, 2nd paragraph). It was determined that patients could be used safely and effectively by these patients (p1078, 1st column, 6th paragraph). Pens are shown to be easier to use than syringes, which is suggested leads to improved adherence and glycemic control (p1078, 1st column, 4th paragraph). This reference discusses using pens to administer the drug.
Therefore, it would be obvious to optimize the pH of the dulaglutide formulations of the competing claims, to reduce aggregation and decomposition pathways, as discussed by Zapadka et al. As pH optimization is standard in polypeptide formulations, an artisan in this field would attempt this process with a reasonable expectation of success.
Furthermore, it would be obvious to formulate the material with Tween 80, phenol, a buffer, and glycerol to further stabilize the formulation, as discussed by both Zapadka et al and Vagenende et al. As these materials are commonly used for this purpose, an artisan in this field would add these ingredients with a reasonable expectation of success.
Finally, it would be obvious to use the pen system of Matfin et al, as an easy way of self-administering the material. As Matfin et al states that such systems work well in other studies, an artisan in this field would attempt this device with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
eighth rejection
Claims 27-30, 34-36, and 41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 42 of copending Application No. 18/523,645 (US 20240197835) in view of Zapadka et al (Interface. Focus (2017) 7:20170030), Vagenende et al (Biochemistry (2009) 48 p11084-11096), and Matfin et al (J. Diabetes Sci. Technol. (2015) 9(5) p1071-1079).
Competing claim 42 describes a therapeutic method using dulaglutide.
The difference between the competing claims and the examined claims is that the competing claims do not specify the formulation.
Zapadka et al discuss the factors affecting the stability of peptide therapeutics (title). Electrostatic interactions are known to play a role in aggregation (p7, 1st column, 5th paragraph), which is controlled by pH and ionic strength (p7, 2nd column, 1st paragraph). In addition, other decomposition mechanisms are dependent on pH (p8, 1st column, 3d paragraph). This strongly suggests optimizing pH of polypeptide formulations for stability. The most commonly used buffers are acetate, citrate, histidine, phosphate, tris, and glycine (p10, 1st column, 4th paragraph). While they may have some formulation issues, Tween 80 (another name for polysorbate 80) is often used to prevent aggregation and absorption (p10, 1st column, 6th paragraph, continues to 2nd column). Preservatives are often used; the most common ones are m-cresol, phenol, and benzyl alcohol (p10, 2nd column, 5th paragraph). Concentration of the polypeptide also plays an important role in stability, affecting aggregation kinetics (p4, 1st column, 1st paragraph). This reference discusses various components and considerations in polypeptide formulations.
Vagenende et al discuss the mechanisms of protein stabilization by glycerol (title). One of the most widely used polyols to stabilize proteins is glycerol, including in biopharmaceuticals (p11084, 2nd column, 2nd paragraph). This excipient reduces polypeptide flexibility, stabilizes partially unfolded intermediates, and reduces aggregation (p11084, 2nd column, 2nd paragraph). This reference discusses glycerol as a polypeptide stabilizer.
Matfin et al discuss once weekly dulaglutide single dose pen usage (title). This was a study to see if patients could use the single dose pen (interpreted as a vial) to treat type 2 diabetes (p1072, 1st column, 2nd paragraph). It was determined that patients could be used safely and effectively by these patients (p1078, 1st column, 6th paragraph). Pens are shown to be easier to use than syringes, which is suggested leads to improved adherence and glycemic control (p1078, 1st column, 4th paragraph). This reference discusses using pens to administer the drug.
Therefore, it would be obvious to optimize the pH of the dulaglutide formulations of the competing claims, to reduce aggregation and decomposition pathways, as discussed by Zapadka et al. As pH optimization is standard in polypeptide formulations, an artisan in this field would attempt this process with a reasonable expectation of success.
Furthermore, it would be obvious to formulate the material with Tween 80, phenol, a buffer, and glycerol to further stabilize the formulation, as discussed by both Zapadka et al and Vagenende et al. As these materials are commonly used for this purpose, an artisan in this field would add these ingredients with a reasonable expectation of success.
Finally, it would be obvious to use the pen system of Matfin et al, as an easy way of self-administering the material. As Matfin et al states that such systems work well in other studies, an artisan in this field would attempt this device with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
ninth rejection
Claims 27-30, 34-36, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-5 of U.S. Patent No. 9,884,093 in view of Zapadka et al (Interface. Focus (2017) 7:20170030), Vagenende et al (Biochemistry (2009) 48 p11084-11096), and Matfin et al (J. Diabetes Sci. Technol. (2015) 9(5) p1071-1079).
Competing claim 1 describes a fusion protein composition, while competing claims 3-5 specify a method using an additional pharmaceutical agent, specifically dulaglutide.
The difference between the competing claims and the examined claims is that the competing claims do not specify the formulation.
Zapadka et al discuss the factors affecting the stability of peptide therapeutics (title). Electrostatic interactions are known to play a role in aggregation (p7, 1st column, 5th paragraph), which is controlled by pH and ionic strength (p7, 2nd column, 1st paragraph). In addition, other decomposition mechanisms are dependent on pH (p8, 1st column, 3d paragraph). This strongly suggests optimizing pH of polypeptide formulations for stability. The most commonly used buffers are acetate, citrate, histidine, phosphate, tris, and glycine (p10, 1st column, 4th paragraph). While they may have some formulation issues, Tween 80 (another name for polysorbate 80) is often used to prevent aggregation and absorption (p10, 1st column, 6th paragraph, continues to 2nd column). Preservatives are often used; the most common ones are m-cresol, phenol, and benzyl alcohol (p10, 2nd column, 5th paragraph). Concentration of the polypeptide also plays an important role in stability,