DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
The amendments and arguments filed 7/30/25 are acknowledged. Claims 5-6, 10-12, 14-15, 17-19, 22, 26-33, 37, 44, 47, 49-50, 53-57, 79, 81-82, and 85 are cancelled. Claims 1, 3, 8-9, 13, 16, 20-21, 23, 34, 39-41, 51-52, 60-61, 64, 68, 70, 78 are amended. Claims 1-4, 7-9, 13, 16, 20-21, 23-25, 34-36, 38-43, 45-46, 48, 51-52, 58-78, 80, 83-84, and 86 are pending.
Claim 86 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 3, 21, 26-32, 76 and 77 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/7/24.
Claims 1-2, 4, 7-9, 13, 16, 20, 23-25, 34-36, 38-43, 45-46, 48, 51-52, 58-75, 78, 80, and 83-84 are currently under consideration for patentability under 37 CFR 1.104.
Information Disclosure Statement
The information disclosure statement filed on 7/30/25 has been considered. A signed copy is enclosed.
Objections Withdrawn
The objection to the abstract is withdrawn in light of Applicant’s amendments thereto.
The objection to claim 1 because of the following informalities: the claim lacks appropriate punctuation to separate the clauses is withdrawn in light of Applicant’s amendments thereto.
The objection to claim 1 because of the following informalities: the term “the said pump” contains the redundant terms “the said” is withdrawn in light of Applicant’s amendments thereto.
The objection to claim 70 and 71 because of the following informalities: the phrase “wherein one or more further reservoirs” should be amended to read “wherein the one or more further reservoirs” is withdrawn in light of Applicant’s amendments thereto.
Claim Rejections Withdrawn
The rejection of claims 1-2, 4, 7-9, 13, 16, 20, 23-25, 34-36, 38-43, 45-46, 48, 51-52, 58-75, 78, 80, and 83 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of Applicant’s amendments thereto. The rejection of claims 12, 14-15, 17, 19, 22, 33, and 53-57 is rendered moot by cancellation of the claims.
The rejection of claims 55-57 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is rendered moot by cancellation of the claims.
The rejection of claim(s) 1-2, 4, 7-9, 13, 16, 20, 34-36, 38-43, 45-46, 48, 51-52, 58, 60, 66-67, 73-75, 78, 80, and 83 under 35 U.S.C. 102(a)(1) as being anticipated by Gerring et al (WO 2017/191464 A1; filed 5/5/17; published 11/9/17) is withdrawn in light of Applicant’s amendments thereto. The rejection of claims 12, 14-15, 17, 19, 22, 33, and 53-57 is rendered moot by cancellation of the claims.
The rejection of claim(s) 1-2, 4, 7-9, 13, 16, 20, 23-25, 34-36, 38-43, 45-46, 48, 51-52, 58-75, 78, 80, and 83 under 35 U.S.C. 103 as being unpatentable over Akers et al (US 2016/0166695 A1) in view of Pillon et al (US 2012/0035103 A1) and Maggio (J. Excipients and Food Chem., 2012, 3(2), 45-53) and further in view of SSED for MiniMed 670G system (published 9/28/16; downloaded from https://www.accessdata.fda.gov/cdrh_docs/pdf16/p160017b.pdf) is withdrawn in light of Applicant’s amendments thereto. The rejection of claims 12, 14-15, 17, 19, 22, 33, and 53-57 is rendered moot by cancellation of the claims.
Claim Rejections Maintained
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.
The rejection of claims 1-2, 4, 7-9, 13, 16, 20, 34-36, 38-43, 46, 51-52, 58-75, 78, 80, and 83-84 on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11,278,624 in view of SSED for MiniMed 670G system (published 9/28/16; downloaded from https://www.accessdata.fda.gov/cdrh_docs/pdf16/p160017b.pdf) is maintained. The rejection of claims 12, 14-15, 17, 19, 22, 33, and 53-57 is rendered moot by cancellation of the claims. Although the claims at issue are not identical, they are not patentably distinct from each other.
The examined claims are summarized above.
The reference patent claims teach an aqueous liquid pharmaceutical formulation comprising an insulin analogue at a concentration of 100-1000 U/ml, ionic zinc at a concentration of 0.25-1% by weight of zinc based on the weight of the insulin analogue in the formulation, citrate as a chelating agent at a concentration of 10-50 mM and polysorbate 80 at a concentration of 0.05-0.5 mg/ml, wherein fewer than 20 particles are detectable in the formulation after 8 weeks at 30° C. using the method described in the 2.9.20 European Pharmacopoeia Monograph (see e.g. claim 1). The insulin can be insulin aspart or insulin glulisine (see e.g. claim 2 and 3). The zinc can be present at a concentration of 0.35-0.75% by weight of zinc based on the weight of insulin analogue in the formulation (see e.g. claim 5). The polysorbate can be present at a concentration of 0.3-0.5 mg/ml or 300-500 μg/ml (see e.g. claim 23). The composition can comprise a tonicity modifying agent such as glycerol (see e.g. claims 10 and 11). The reference patent does not teach concentration specifically less than 10 mM of chloride, but choosing a suitable concentration is considered as an optimizable parameter and therefore it is obvious.
The reference patent teaches same components in the formulation and the ionic strength is expected to be less than 40 mM. The ionic strength can be calculated from several ways, if applicants think the cited formula is critical or novel, then applicants need to explain, otherwise this limitation is redundant, absent evidence to the contrary.
The reference patent teaches that the pH can be 7.6-8.0 (see e.g. claim 15). The composition can have a preservative such as phenol (see e.g. claim 17).
Regarding the limitations of instant claims 55-57, the claimed limitations are inherent functional properties of a formulation having the same components and concentrations as the instant claims.
Regarding treating diabetes, the reference patent teaches treatment of diabetes mellitus in a subject (see e.g. claim 19).
Generally, differences in concentrations of components of a formulation will not support the patentability of subject matter encompassed by the prior art, or in this case the reference patent. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Alter, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
Based on the above established facts from the cited reference patent, it appears that all the claimed elements, e.g., applicants individual components in the composition etc., were known in the reference patent, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art. Furthermore, the concentrations of the reference patent overlaps for formulation components with the instant claimed ranges. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed composition with a reasonable expectation of success. The motivation to combine the components into the claimed formulation can arise from the expectation that the reference patent elements will perform their expected functions to achieve their expected results when combined for their commonly known purpose. See MPEP 2144.07.
The reference patent does not teach the use of a pump system with the features of the instant claims.
SSED from the FDA teaches the MiniMed 670G system, which is used for insulin bolus doses for management of Type I diabetes mellitus (see e.g. page 1).
SSED teaches that the system can be programmed to automatically adjust delivery of basal insulin based on continuous glucose monitor sensor glucose values (see e.g. page 1).
SSED teaches that glucose is monitored by The Guardian Sensor (see e.g. page 2). The pump is compatible with paradigm reservoirs which can hold 3 mL volume reservoirs (see e.g. page 7).
SSED teaches that the system is a closed loop system (see e.g. page 2).
The instant specification indicates that the MiniMed 670G system is a traditional tethered pump is worn in a pocket or clipped to a belt and uses a fine tubing to connect the pump to the cannula. The pump body contains buttons that allow programming the insulin delivery at a slow, continuous (basal) rate as well as in supplemental (bolus) doses before meals or suspending the insulin infusion, if necessary (see instant specification page 4). The MiniMed pump can deliver insulin subcutaneously (see e.g. SSED page 3). The MiniMed system is automated, indicating that the device has a control for delivering dosing (see e.g. SSED page 69). Further, instant specification Example 9 indicates that the MiniMed system meets the limitations of the claims (see e.g. instant specification age 54).
It would have been obvious to one with ordinary skill in the art, at the time of the invention, to use a pump such as the MiniMed pump to deliver the formulation of the reference patent because the Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The SSED document demonstrates the known use of pumps for continuous subcutaneous delivery of insulin. The MiniMed pump can be programmed to automatically calculate the insulin dose, based on information received from the glucose monitor, to achieve glycemic control throughout the day and night. The MiniMed pump can deliver the formulation of the reference patent without alterations to components or functions. Further, the advantages of automatic adjustment of insulin delivery, and continuous glucose monitoring to identify correct insulin dosing provides motivation for one of skill in the art to use the MiniMed pump with the formulation of the reference patent. Thus, the combination of references as described above provided a prima facie case of obviousness, absent convincing evidence to the contrary.
The provisional rejection of claims 1-2, 4, 7-9, 13, 16, 20, 23-25, 34-36, 38-43, 45-46, 48, 51-52, 58-75, 78, 80, and 83-84 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7, 11, 14-17, 19-27, 30, 34, 36, 38-39, 41, 44-47, 49-52, 70-73, 76-83 of copending Application No. 16/337,706 (reference application) in view of SSED for MiniMed 670G system (published 9/28/16; downloaded from https://www.accessdata.fda.gov/cdrh_docs/pdf16/p160017b.pdf) is maintained. The rejection of claims 12, 14-15, 17, 19, 22, 33, and 53-57 is rendered moot by cancellation of the claims. Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The examined claims are summarized above.
The copending application claims an aqueous liquid pharmaceutical formulation comprising:(i) an insulin compound selected from the group consisting of insulin lispro, insulin glulisine, insulin aspart, insulin glargine, and recombinant human insulin, (ii) ionic zinc,(iii) a zinc binding species at a concentration of 1- 60 mM and having a logK with respect to zinc ion binding in the range 4.5-12.3 at 25 °C, and(iv) an alkyl glycoside at a concentration of 10-200 μg/ml, and() a charged tonicity modifier at a concentration of 100-300 mM; wherein the formulation concentration of the zinc binding species having a logK with respect to zinc ion binding of more than 12.3 at 25 °C is less than 0.1 mM; and wherein the formulation is for subcutaneous or intramuscular administration, but the formulation is not for administration by intranasal delivery (see e.g. claim 1). The insulin can be insulin lispro, insulin glulisine, or recombinant human insulin (see e.g. claim 3). The insulin compound can have a concentration of 50-300 U/ml (see e.g. claim 7). The ionic zinc is present at a concentration of 0.05-1%, by weight of zinc based on the weight of insulin compound in the formulation (see e.g. claim 11). The zinc binding species can be citrate, pyrophosphate, aspartate, glutamate, cysteine, cystine, glutathione, ethylenediamine, histidine, DETA and TETA (see e.g. claim 14). The source of the citrate can be citric acid (see e.g. claim 16). The molar ratio of ionic zinc to zinc binding can be 1:3 to 1:175 (see e.g. claim 17). .
The zinc binding species can be at a concentration of 1 - 60 mM and has a logK with respect to zinc ion binding in the range 4.5-10 at 25 °C (see e.g. claim 19). .
The alkyl glycoside is selected from the group: dodecyl maltoside, dodecyl glucoside, octyl glucoside, octyl maltoside, decyl glucoside, decyl maltoside, decyl glucopyranoside, tridecyl glucoside,tridecyl maltoside, tetradecyl glucoside, tetradecyl maltoside, hexadecyl glucoside, hexadecyl maltoside, sucrose monooctanoate, sucrose monodecanoate, sucrose monododecanoate, sucrose monotridecanoate, sucrose monotetradecanoate, and sucrose monohexadecanoate (see e.g. claim 21). The alkyl glycoside is present at a concentration of 20-200 μg/ml (see e.g. claim 24).The pH is in the range 7.0 to 7.5 or 7.6 to 8.0 (see e.g. claim 36).The formulation can comprise a phosphate buffer (see e.g. claim 38. The formulation can comprise at least one preservative selected from the group: phenol, m-cresol, chlorocresol, benzyl alcohol, propylparaben, methylparaben, benzalkonium chloride, and benzethonium chloride (see e.g. claim 39). The formulation can comprise nicotinamide (see e.g. claim 41). The citrate is present in the formulation at a concentration of 10-30 mM (see e.g. claim 45) or 30-50 mM (see e.g. claim 47). The reference claims are further drawn to a method of treatment of diabetes mellitus which comprises administering to a subject in need thereof an effective amount of the formulation (see e.g. claim 49). The claims further recite an injection device for single or multiple uses comprising a container with doses, and a pump for automatic or remote operation (see e.g. claims 51-52). The formulation can be administered with another agent such as amylin analogue or GLP-1 agonist (see e.g. claim 72). The alkyl glycoside is present at a concentration of 20-200 μg/ml (see e.g. claim 74).The formulation is for subcutaneous administration (see e.g. claim 76). The insulin composition is at a concentration of 100-200 U/ml (see e.g. claim 78).
Generally, differences in concentrations of components of a formulation will not support the patentability of subject matter encompassed by the prior art, or in this case the reference application. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Alter, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
Based on the above established facts from the cited reference patent, it appears that all the claimed elements, e.g., individual components in the composition etc., were known in the reference application, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art. Furthermore, the concentrations of the reference claims overlaps for formulation components with the instant claimed ranges. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed composition with a reasonable expectation of success. The motivation to combine the components into the claimed formulation can arise from the expectation that the reference application elements will perform their expected functions to achieve their expected results when combined for their commonly known purpose. See MPEP 2144.07.
The reference application does not teach the use of a pump system with the features of the instant claims.
SSED from the FDA teaches the MiniMed 670G system, which is used for insulin bolus doses for management of Type I diabetes mellitus (see e.g. page 1).
SSED teaches that the system can be programmed to automatically adjust delivery of basal insulin based on continuous glucose monitor sensor glucose values (see e.g. page 1).
SSED teaches that glucose is monitored by The Guardian Sensor (see e.g. page 2). The pump is compatible with paradigm reservoirs which can hold 3 mL volume reservoirs (see e.g. page 7).
SSED teaches that the system is a closed loop system (see e.g. page 2).
The instant specification indicates that the MiniMed 670G system is a traditional tethered pump is worn in a pocket or clipped to a belt and uses a fine tubing to connect the pump to the cannula. The pump body contains buttons that allow programming the insulin delivery at a slow, continuous (basal) rate as well as in supplemental (bolus) doses before meals or suspending the insulin infusion, if necessary (see instant specification page 4). The MiniMed pump can deliver insulin subcutaneously (see e.g. SSED page 3). The MiniMed system is automated, indicating that the device has a control for delivering dosing (see e.g. SSED page 69). Further, instant specification Example 9 indicates that the MiniMed system meets the limitations of the claims (see e.g. instant specification age 54).
It would have been obvious to one with ordinary skill in the art, at the time of the invention, to use a pump such as the MiniMed pump to deliver the formulation of the reference application because the Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The SSED document demonstrates the known use of pumps for continuous subcutaneous delivery of insulin. The MiniMed pump can be programmed to automatically calculate the insulin dose, based on information received from the CGM, to achieve glycemic control throughout the day and night. The MiniMed pump can deliver the formulation of the reference patent without alterations to components or functions. Further, the advantages of automatic adjustment of insulin delivery, and continuous glucose monitoring to identify correct insulin dosing provides motivation for one of skill in the art to use the MiniMed pump with the formulation of the reference application. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
The provisional rejection of claims 1-2, 4, 7-9, 13, 16, 20, 23-25, 34-36, 38-43, 45-46, 48, 51-52, 58-75, 78, 80, and 83-84 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-7, 10-11, 15-22, 24-26, 34-36, 38-42, 44-45, 47, 50-51, 69-85, 88-95 of copending Application No. 16/337,730 (reference application) in view of SSED for MiniMed 670G system (published 9/28/16; downloaded from https://www.accessdata.fda.gov/cdrh_docs/pdf16/p160017b.pdf) is maintained. The rejection of claims 12, 14-15, 17, 19, 22, 33, and 53-57 is rendered moot by cancellation of the claims. Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The examined claims have been summarized above.
The copending application claims an aqueous liquid pharmaceutical formulation comprising:(i) an insulin compound selected from the group consisting of insulin lispro, insulin glulisine, insulin aspart, insulin glargine, and recombinant human insulin, (ii) ionic zinc at a concentration of 0.5-1% based on weight of insulin compound ,(iii) a zinc binding species at a concentration of 1- 60 mM and having a logK with respect to zinc ion binding in the range 4.5-12.3 at 25 °C, and(iv) an alkyl glycoside at a concentration of 10-200 μg/ml, wherein the formulation contains less than 8mM chloride and has less than 0.1 mM of any zinc binding species with a logK of more than 12.3. (see e.g. claim 1). The ionic strength can be calculated with the same formula as the instant claims (see e.g. claim 2). The insulin can be insulin aspart (see e.g. claim 7). The insulin compound can have a concentration of 500-1000 U/ml (see e.g. claim 10). The zinc binding species can be citrate, pyrophosphate, aspartate, glutamate, cysteine, cystine, glutathione, ethylenediamine, histidine, DETA and TETA (see e.g. claim 15). The source of the citrate can be citric acid (see e.g. claim 16). The molar ratio of ionic zinc to zinc binding can be 1:3 to 1:175 (see e.g. claim 20).
The alkyl glycoside is selected from the group: dodecyl maltoside, dodecyl glucoside, octyl glucoside, octyl maltoside, decyl glucoside, decyl maltoside, decyl glucopyranoside, tridecyl glucoside,tridecyl maltoside, tetradecyl glucoside, tetradecyl maltoside, hexadecyl glucoside, hexadecyl maltoside, sucrose monooctanoate, sucrose monodecanoate, sucrose monododecanoate, sucrose monotridecanoate, sucrose monotetradecanoate, and sucrose monohexadecanoate (see e.g. claim 24). The alkyl glycoside is present at a concentration of 20-200 μg/ml (see e.g. claim 34).The pH is in the range 7.0 to 7.5 or 7.6 to 8.0 (see e.g. claim 42).The formulation can have a tonicity modifying agent such as glycerol (see e.g. claims 36 and 38). The formulation can comprise a phosphate buffer (see e.g. claim 44). The formulation can comprise at least one preservative selected from the group: phenol, m-cresol, chlorocresol, benzyl alcohol, propylparaben, methylparaben, benzalkonium chloride, and benzethonium chloride (see e.g. claim 45). The formulation can be administered with another agent such as amylin analogue or GLP-1 agonist (see e.g. claim 71). The formulation is for subcutaneous administration (see e.g. claim 92).
The copending specification teaches that the formulation can be used to treat diabetes mellitus (see e.g. page 1 and 6 of the copending specification). The Federal Circuit has held that obviousness-type double patenting exists for method claims that simply claim the disclosed use of a composition in the specification. See Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010). The instant application and the copending application are not divisional applications resulting from restriction, and therefore no protection under the provisions of 35 USC 121.
Generally, differences in concentrations of components of a formulation will not support the patentability of subject matter encompassed by the prior art, or in this case the reference application. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Alter, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
Based on the above established facts from the cited reference patent, it appears that all the claimed elements, e.g., individual components in the composition etc., were known in the reference application, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art. Furthermore, the concentrations of the reference claims overlaps for formulation components with the instant claimed ranges. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed composition with a reasonable expectation of success. The motivation to combine the components into the claimed formulation can arise from the expectation that the reference application elements will perform their expected functions to achieve their expected results when combined for their commonly known purpose. See MPEP 2144.07.
The reference application does not teach the use of a pump system with the features of the instant claims.
SSED from the FDA teaches the MiniMed 670G system, which is used for insulin bolus doses for management of Type I diabetes mellitus (see e.g. page 1).
SSED teaches that the system can be programmed to automatically adjust delivery of basal insulin based on continuous glucose monitor sensor glucose values (see e.g. page 1).
SSED teaches that glucose is monitored by The Guardian Sensor (see e.g. page 2). The pump is compatible with paradigm reservoirs which can hold 3 mL volume reservoirs (see e.g. page 7).
SSED teaches that the system is a closed loop system (see e.g. page 2).
The instant specification indicates that the MiniMed 670G system is a traditional tethered pump is worn in a pocket or clipped to a belt and uses a fine tubing to connect the pump to the cannula. The pump body contains buttons that allow programming the insulin delivery at a slow, continuous (basal) rate as well as in supplemental (bolus) doses before meals or suspending the insulin infusion, if necessary (see instant specification page 4). The MiniMed pump can deliver insulin subcutaneously (see e.g. SSED page 3). The MiniMed system is automated, indicating that the device has a control for delivering dosing (see e.g. SSED page 69). Further, instant specification Example 9 indicates that the MiniMed system meets the limitations of the claims (see e.g. instant specification age 54).
It would have been obvious to one with ordinary skill in the art, at the time of the invention, to use a pump such as the MiniMed pump to deliver the formulation of the reference application because the Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The SSED document demonstrates the known use of pumps for continuous subcutaneous delivery of insulin. The MiniMed pump can be programmed to automatically calculate the insulin dose, based on information received from the CGM, to achieve glycemic control throughout the day and night. The MiniMed pump can deliver the formulation of the reference application without alterations to components or functions. Further, the advantages of automatic adjustment of insulin delivery, and continuous glucose monitoring to identify correct insulin dosing provides motivation for one of skill in the art to use the MiniMed pump with the formulation of the reference application. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
The provisional rejection of claims 1-2, 4, 7-9, 16, 23-25, 34-35, 39-43, 46, 48, 58-75, 78, 80, and 83-84 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6, 10-12, 14-16, 25-31, 35-36, 38-41, 43, 47, 55-61, and 65 of copending Application No. 16/610,826 (reference application) in view of SSED for MiniMed 670G system (published 9/28/16; downloaded from https://www.accessdata.fda.gov/cdrh_docs/pdf16/p160017b.pdf) is maintained. The rejection of claims 12, 14-15, 17, 19, 22, 33, and 53-57 is rendered moot by cancellation of the claims. Although the claims at issue are not identical, they are not patentably distinct from each other
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The examined claims are summarized above.
The copending application claims an aqueous liquid pharmaceutical formulation comprising:(i) an insulin compound selected from the group consisting of insulin lispro, insulin aspart, and recombinant human insulin, (ii) ionic zinc at a concentration of 0.5-1% weight of zinc based on weight of insulin,(iii) a zinc binding species at a concentration of 1mM or more and having a logK with respect to zinc ion binding in the range 4.5-10.0 at 25 °C, a (iv) a zinc binding species at less than 0.3 mM, having a logK with respect to zinc ion binding of more than12.3 at 25 °C, and (v) an alkyl glycoside at a concentration of 10-200 μg/ml. The insulin compound can have a concentration of 10-1000 U/ml (see e.g. claim 7). The zinc binding species in the range of 4.5-10 at 25 °C can be citrate (see e.g. claim 10), and can have a concentration of 1-50 mM (see e.g. claim 12).
The alkyl glycoside is selected from the group: dodecyl maltoside, dodecyl glucoside, octyl glucoside, octyl maltoside, decyl glucoside, decyl maltoside, decyl glucopyranoside, tridecyl glucoside,tridecyl maltoside, tetradecyl glucoside, tetradecyl maltoside, hexadecyl glucoside, hexadecyl maltoside, sucrose monooctanoate, sucrose monodecanoate, sucrose monododecanoate, sucrose monotridecanoate, sucrose monotetradecanoate, and sucrose monohexadecanoate (see e.g. claim 15). The alkyl glycoside is present at a concentration of 10-100 μg/ml (see e.g. claim 24).The formulation can comprise a tonicity modifier such as sodium chloride (see e.g. claims 31 and 36). The formulation can be isotonic (see e.g. claim 39). The pH is in the range 5.5 to 9.0 (see e.g. claim 40).The formulation can comprise a phosphate buffer (see e.g. claim 38. The formulation can comprise at least one preservative selected from the group: phenol, m-cresol, chlorocresol, benzyl alcohol, propylparaben, methylparaben, benzalkonium chloride, and benzethonium chloride (see e.g. claim 41). The formulation can comprise nicotinamide (see e.g. claim 43). The molar ratio of ionic zinc to citrate is 1:3 to 1:500 (see e.g. claim 56).
The reference claims are further drawn to a method of treatment of diabetes mellitus which comprises administering to a subject in need thereof an effective amount of the formulation (see e.g. claim 47).
Generally, differences in concentrations of components of a formulation will not support the patentability of subject matter encompassed by the prior art, or in this case the reference application. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Alter, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
Based on the above established facts from the cited reference patent, it appears that all the claimed elements, e.g., individual components in the composition etc., were known in the reference application, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art. Furthermore, the concentrations of the reference claims overlaps for formulation components with the instant claimed ranges. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed composition with a reasonable expectation of success. The motivation to combine the components into the claimed formulation can arise from the expectation that the reference application elements will perform their expected functions to achieve their expected results when combined for their commonly known purpose. See MPEP 2144.07.
The reference application does not teach the use of a pump system with the features of the instant claims.
SSED from the FDA teaches the MiniMed 670G system, which is used for insulin bolus doses for management of Type I diabetes mellitus (see e.g. page 1).
SSED teaches that the system can be programmed to automatically adjust delivery of basal insulin based on continuous glucose monitor sensor glucose values (see e.g. page 1).
SSED teaches that glucose is monitored by The Guardian Sensor (see e.g. page 2). The pump is compatible with paradigm reservoirs which can hold 3 mL volume reservoirs (see e.g. page 7).
SSED teaches that the system is a closed loop system (see e.g. page 2).
The instant specification indicates that the MiniMed 670G system is a traditional tethered pump is worn in a pocket or clipped to a belt and uses a fine tubing to connect the pump to the cannula. The pump body contains buttons that allow programming the insulin delivery at a slow, continuous (basal) rate as well as in supplemental (bolus) doses before meals or suspending the insulin infusion, if necessary (see instant specification page 4). The MiniMed pump can deliver insulin subcutaneously (see e.g. SSED page 3). The MiniMed system is automated, indicating that the device has a control for delivering dosing (see e.g. SSED page 69). Further, instant specification Example 9 indicates that the MiniMed system meets the limitations of the claims (see e.g. instant specification age 54).
It would have been obvious to one with ordinary skill in the art, at the time of the invention, to use a pump such as the MiniMed pump to deliver the formulation of the reference application because the Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The SSED document demonstrates the known use of pumps for continuous subcutaneous delivery of insulin. The MiniMed pump can be programmed to automatically calculate the insulin dose, based on information received from the CGM, to achieve glycemic control throughout the day and night. The MiniMed pump can deliver the formulation of the reference patent without alterations to components or functions. Further, the advantages of automatic adjustment of insulin delivery, and continuous glucose monitoring to identify correct insulin dosing provides motivation for one of skill in the art to use the MiniMed pump with the formulation of the reference application. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
The provisional rejection of claims 1-2, 4, 7-9, 13, 16, 20, 23-25, 34-36, 38-43, 45-46, 48, 51-52, 58-75, 78, 80, and 83-84 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 8, 13, 16-21, 23-31, 33-34, 36-39, 42-43, 45, 48-78, 80, 83, and 88 of copending Application No. 17/044,706 (reference application) is maintained. The rejection of claims 12, 14-15, 17, 19, 22, 33, and 53-57 is rendered moot by cancellation of the claims. Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The examined claims are summarized above.
The copending application claims a medical infusion pump system comprising a pump and a reservoir comprising an aqueous liquid pharmaceutical formulation comprising:(i) an insulin compound selected from the group consisting of insulin lispro, insulin aspart, and insulin glulisine, (ii) ionic zinc at a concentration of 0.5-1% weight of zinc based on weight of insulin,(iii) an alkyl glycoside at a concentration of 10-100 μg/ml (iv) citrate at a concentration of 10-60 mM, and (v) a tonicity modifying agent (see e.g. claim 1). The insulin compound can have a concentration of 50-200 U/ml or 500-1000 U/ml (see e.g. claim 7). The tonicity modifying agent can have a concentration of 100-300 mM and can be sodium chloride (see e.g. claim 1). The source of the citrate can be citric acid (see e.g. claim 20). The molar ratio of ionic zinc to citrate can be 1:30 to 1:175 (see e.g. claim 21). The alkyl glycoside can be dodecyl maltoside (see e.g. claim 25). The tonicity modifying agent can be glycerol (see e.g. claim 31). The ionic strength can be calculated with the same formula as the instant claims (see e.g. claim 37). The composition can be isotonic (see e.g. claim 38). The pH is in the range 5.5 to 9.0 (see e.g. claim 39).The formulation can comprise a phosphate buffer (see e.g. claim 42). The formulation can comprise at least one preservative selected from the group: phenol, m-cresol, chlorocresol, benzyl alcohol, propylparaben, methylparaben, benzalkonium chloride, and benzethonium chloride (see e.g. claim 43). The formulation can comprise nicotinamide (see e.g. claim 45). The composition can be substantially free of EDTA (see e.g. claim 48). The same comparison regarding bioequivalence to a standard composition can be made as in the instant claims (see e.g. claims 55-57). The pump can have a controller, the same basal rate and same pulse volumes and frequency as the instant claims (see e.g. claims 58-68). The pump can have additional reservoirs with additional active agents (see e.g. claims 68-71). The pump can been closed or open loop, worn on the surface of the body, and can have a needle or cannula in fluid communication with the pump or reservoir (see e.g. claims 72-77). The pump can comprise a glucose sensor (see e.g. claim 78). The administration can be subcutaneous (see e.g. claim 80).
The reference claims are further drawn to a method of treatment of diabetes mellitus which comprises administering to a subject in need thereof an effective amount of the formulation (see e.g. claim 83).
The reference claims differ from the instant claims because the reference claims specific component species and narrower ranges of concentrations. The instant application recites broader genera of components with wider ranges of concentrations. Therefore, the reference application claims species of the instant claims, and while the scope of the claim sets overlap, it is not identical.
Generally, differences in concentrations of components of a formulation will not support the patentability of subject matter encompassed by the prior art, or in this case the reference application. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Alter, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
Based on the above established facts from the cited reference patent, it appears that all the claimed elements, e.g., individual components in the composition etc., were known in the reference application, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art. Furthermore, the concentrations of the reference claims overlaps for formulation components with the instant claimed ranges. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed composition with a reasonable expectation of success. The motivation to combine the components into the claimed formulation can arise from the expectation that the reference application elements will perform their expected functions to achieve their expected results when combined for their commonly known purpose. See MPEP 2144.07.
The provisional rejection of claims 1-2, 4, 7-9, 16, 23-25, 34-35, 39-43, 46, 48, 58-75, 78, 80, and 83-84 on the ground of nonstatutory double patenting as being unpatentable over claims 3, 6, 9-11, 13-19, 21-23, 25-27, 29, 34, 36-37, 39-40, 43-46, 48-49, 51, 54-55, 57, 68-71 of copending Application No. 17/916,504 (reference application) in view of SSED for MiniMed 670G system (published 9/28/16; downloaded from https://www.accessdata.fda.gov/cdrh_docs/pdf16/p160017b.pdf) is maintained. The rejection of claims 12, 14-15, 17, 19, 22, 33, and 53-57 is rendered moot by cancellation of the claims. Although the claims at issue are not identical, they are not patentably distinct from each other
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The examined claims are summarized above.
The copending application claims a method of treating a human subject suffering from diabetes mellitus by administering an aqueous liquid pharmaceutical formulation comprising:(i) an insulin analogue (ii) ionic zinc (iii) citrate, with the formulation being substantially free of a zinc binding species having a logK with respect to zinc ion binding above 12.3 at 25 °C, wherein the administration is by subcutaneous infusion at a dose of 0.3 U/kg (see e.g. claim 3, 6, and 9). The insulin can be insulin aspart (see e.g. claim 10). The insulin can be present at 50-200 U/ml (see e.g. claim 13). The ionic zinc is present at more than 0.5% by weight of zinc compared to insulin analogue (see e.g. claim 15-17). The source of the citrate can be citric acid (see e.g. claim 18). The citrate can be present at a concentration of 1-50 mM (see e.g. claim 19). The formulation can have a non-ionic surfactant that can be an alkyl glycoside, and the alkyl glycoside is selected from the group: dodecyl maltoside, dodecyl glucoside, octyl glucoside, octyl maltoside, decyl glucoside, decyl maltoside, decyl glucopyranoside, tridecyl glucoside,tridecyl maltoside, tetradecyl glucoside, tetradecyl maltoside, hexadecyl glucoside, hexadecyl maltoside, sucrose monooctanoate, sucrose monodecanoate, sucrose monododecanoate, sucrose monotridecanoate, sucrose monotetradecanoate, and sucrose monohexadecanoate (see e.g. claim 22-23). The alkyl glycoside is present at a concentration of 1-1000 μg/ml (see e.g. claim 24).The formulation can comprise a tonicity modifier such as glycerol (see e.g. claims 36 and 37). The ionic strength can be calculated using the same formula as the instant claims (see e.g. claim 43). The formulation can be isotonic (see e.g. claim 44). The pH is in the range 5.5 to 9.0 (see e.g. claim 45 and 46). The formulation can comprise a phosphate buffer (see e.g. claim 48). The formulation can comprise at least one preservative selected from the group: phenol, m-cresol, chlorocresol, benzyl alcohol, propylparaben, methylparaben, benzalkonium chloride, and benzethonium chloride (see e.g. claim 49). The formulation can comprise nicotinamide (see e.g. claim 51). The formulation can comprise an additional agent (see e.g. claim 55). The composition can be administered as a bolus (see e.g. claim 71).
Generally, differences in concentrations of components of a formulation will not support the patentability of subject matter encompassed by the prior art, or in this case the reference application. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Alter, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
Based on the above established facts from the cited reference patent, it appears that all the claimed elements, e.g., individual components in the composition etc., were known in the reference application, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art. Furthermore, the concentrations of the reference claims overlaps for formulation components with the instant claimed ranges. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed composition with a reasonable expectation of success. The motivation to combine the components into the claimed formulation can arise from the expectation that the reference application elements will perform their expected functions to achieve their expected results when combined for their commonly known purpose. See MPEP 2144.07.
The reference application does not teach the use of a pump system with the features of the instant claims.
SSED from the FDA teaches the MiniMed 670G system, which is used for insulin bolus doses for management of Type I diabetes mellitus (see e.g. page 1).
SSED teaches that the system can be programmed to automatically adjust delivery of basal insulin based on continuous glucose monitor sensor glucose values (see e.g. page 1).
SSED teaches that glucose is monitored by The Guardian Sensor (see e.g. page 2). The pump is compatible with paradigm reservoirs which can hold 3 mL volume reservoirs (see e.g. page 7).
SSED teaches that the system is a closed loop system (see e.g. page 2).
The instant specification indicates that the MiniMed 670G system is a traditional tethered pump is worn in a pocket or clipped to a belt and uses a fine tubing to connect the pump to the cannula. The pump body contains buttons that allow programming the insulin delivery at a slow, continuous (basal) rate as well as in supplemental (bolus) doses before meals or suspending the insulin infusion, if necessary (see instant specification page 4). The MiniMed pump can deliver insulin subcutaneously (see e.g. SSED page 3). The MiniMed system is automated, indicating that the device has a control for delivering dosing (see e.g. SSED page 69). Further, instant specification Example 9 indicates that the MiniMed system meets the limitations of the claims (see e.g. instant specification age 54).
It would have been obvious to one with ordinary skill in the art, at the time of the invention, to use a pump such as the MiniMed pump to deliver the formulation of the reference application because the Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The SSED document demonstrates the known use of pumps for continuous subcutaneous delivery of insulin. The MiniMed pump can be programmed to automatically calculate the insulin dose, based on information received from the CGM, to achieve glycemic control throughout the day and night. The MiniMed pump can deliver the formulation of the reference patent without alterations to components or functions. Further, the advantages of automatic adjustment of insulin delivery, and continuous glucose monitoring to identify correct insulin dosing provides motivation for one of skill in the art to use the MiniMed pump with the formulation of the reference application. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
The provisional rejection of claim 1-2, 4, 7-9, 16, 34-35, 39-43, 46, 58-75, 78, 80, and 83-84 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 8-9, 13-15, 19-34 of copending Application No. 18/750,669 (reference application) in view of SSED for MiniMed 670G system (published 9/28/16; downloaded from https://www.accessdata.fda.gov/cdrh_docs/pdf16/p160017b.pdf) is maintained. The rejection of claims 12, 14-15, 17, 19, 22, 33, and 53-57 is rendered moot by cancellation of the claims. Although the claims at issue are not identical, they are not patentably distinct from each other
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The examined claims are summarized above.
The copending application claims an aqueous liquid pharmaceutical formulation comprising:(i) an insulin analogue such as insulin aspart (ii) ionic zinc at a concentration of 0.25-1% by weight of zinc compared to weight of insulin analogue (iii) citrate at a concentration of 10-50 mM; (iv) polysorbate 80 at a concentration of 1-500μg/ml, (see e.g. claim 1-4). The source of the citrate can be citric acid (see e.g. claim 13). The composition can have a tonicity modifier such as glycerol (see e.g. claim 21-22). The formulation can be isotonic (see e.g. claim 23). The pH is in the range 7.6-8.0 (see e.g. claim 26). The formulation can comprise at least one preservative selected from the group: phenol, m-cresol, chlorocresol, benzyl alcohol, propylparaben, methylparaben, benzalkonium chloride, and benzethonium chloride (see e.g. claim28). The ionic strength can be calculated from several ways, if applicants think the cited formula is critical or novel, then applicants need to explain, otherwise this limitation is redundant, absent evidence to the contrary. Regarding the limitations of instant claims 55-57, the claimed limitations are inherent functional properties of a formulation having the same components and concentrations as the instant claims.
The reference claims are further drawn to a method of treatment of diabetes mellitus which comprises administering to a subject in need thereof an effective amount of the formulation (see e.g. claim 30).
Generally, differences in concentrations of components of a formulation will not support the patentability of subject matter encompassed by the prior art, or in this case the reference application. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Alter, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
Based on the above established facts from the cited reference patent, it appears that all the claimed elements, e.g., individual components in the composition etc., were known in the reference application, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art. Furthermore, the concentrations of the reference claims overlaps for formulation components with the instant claimed ranges. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed composition with a reasonable expectation of success. The motivation to combine the components into the claimed formulation can arise from the expectation that the reference application elements will perform their expected functions to achieve their expected results when combined for their commonly known purpose. See MPEP 2144.07.
The reference application does not teach the use of a pump system with the features of the instant claims.
SSED from the FDA teaches the MiniMed 670G system, which is used for insulin bolus doses for management of Type I diabetes mellitus (see e.g. page 1).
SSED teaches that the system can be programmed to automatically adjust delivery of basal insulin based on continuous glucose monitor sensor glucose values (see e.g. page 1).
SSED teaches that glucose is monitored by The Guardian Sensor (see e.g. page 2). The pump is compatible with paradigm reservoirs which can hold 3 mL volume reservoirs (see e.g. page 7).
SSED teaches that the system is a closed loop system (see e.g. page 2).
The instant specification indicates that the MiniMed 670G system is a traditional tethered pump is worn in a pocket or clipped to a belt and uses a fine tubing to connect the pump to the cannula. The pump body contains buttons that allow programming the insulin delivery at a slow, continuous (basal) rate as well as in supplemental (bolus) doses before meals or suspending the insulin infusion, if necessary (see instant specification page 4). The MiniMed pump can deliver insulin subcutaneously (see e.g. SSED page 3). The MiniMed system is automated, indicating that the device has a control for delivering dosing (see e.g. SSED page 69). Further, instant specification Example 9 indicates that the MiniMed system meets the limitations of the claims (see e.g. instant specification age 54).
It would have been obvious to one with ordinary skill in the art, at the time of the invention, to use a pump such as the MiniMed pump to deliver the formulation of the reference application because the Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The SSED document demonstrates the known use of pumps for continuous subcutaneous delivery of insulin. The MiniMed pump can be programmed to automatically calculate the insulin dose, based on information received from the CGM, to achieve glycemic control throughout the day and night. The MiniMed pump can deliver the formulation of the reference patent without alterations to components or functions. Further, the advantages of automatic adjustment of insulin delivery, and continuous glucose monitoring to identify correct insulin dosing provides motivation for one of skill in the art to use the MiniMed pump with the formulation of the reference application. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
The provisional rejection of claims 1-2, 4, 7-9, 13, 20, 23-25, 34-36, 38-43, 45-46, 48, 51-52, 58-75, 78, 80, and 83-84 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7, 22-24, 26, 31, 34-36, 38, 41-44 and 51 of copending Application No. 19/009,689 (reference application) in view of SSED for MiniMed 670G system (published 9/28/16; downloaded from https://www.accessdata.fda.gov/cdrh_docs/pdf16/p160017b.pdf) is maintained. The rejection of claims 12, 14-15, 17, 19, 22, 33, and 53-57 is rendered moot by cancellation of the claims. Although the claims at issue are not identical, they are not patentably distinct from each other
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The examined claims are summarized above.
The copending application claims an aqueous liquid pharmaceutical formulation comprising: An aqueous liquid pharmaceutical formulation comprising (i) an insulin compound, (ii) ionic zinc, (iii) a nicotinic compound (iv) a non-ionic surfactant; and (v) a salt selected from the salts formed between Group 1 metals and a mono or divalent anion (see e.g. claim 1). The insulin compound can be insulin aspart (see e.g. claim 3). The insulin can be present in a concentration of 10-1000 U/ml (see e.g. claim 6). The nicotinic compound can be nicotinamide (see e.g. claim 7). The non-ionic surfactant can be an alkyl glycoside (see e.g. claim 10), such as dodecyl maltoside (see e.g. claim 11). The surfactant can be present at a concentration of 10-100 μg/ml (see e.g. claim 21). The zinc can be present at a concentration of 0.05% or more by weight of the zinc compared to insulin compound (see e.g. claim 29). The composition can have a tonicity modifier such as glycerol (see e.g. claim 31-33). The formulation can be isotonic (see e.g. claim 34). The pH is in the range 5.5-9.0 (see e.g. claim 35). The formulation can comprise at least one preservative selected from the group: phenol, m-cresol, chlorocresol, benzyl alcohol, propylparaben, methylparaben, benzalkonium chloride, and benzethonium chloride (see e.g. claims 37-38). The ionic strength can be calculated from several ways, if applicants think the cited formula is critical or novel, then applicants need to explain, otherwise this limitation is redundant, absent evidence to the contrary. Regarding the limitations of instant claims 55-57, the claimed limitations are inherent functional properties of a formulation having the same components and concentrations as the instant claims.
The reference claims are further drawn to a method of treatment of diabetes mellitus which comprises administering to a subject in need thereof an effective amount of the formulation (see e.g. claim 41). The reference claims further recite an injection device for single or multiple uses with an injection needle (see e.g. claim 43). The reference claims further recite a medical device comprising a reservoir with a pump for automatic or remote operation to administer the formulation (see e.g. claim 44).
Generally, differences in concentrations of components of a formulation will not support the patentability of subject matter encompassed by the prior art, or in this case the reference application. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Alter, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
Based on the above established facts from the cited reference patent, it appears that all the claimed elements, e.g., individual components in the composition etc., were known in the reference application, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art. Furthermore, the concentrations of the reference claims overlaps for formulation components with the instant claimed ranges. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed composition with a reasonable expectation of success. The motivation to combine the components into the claimed formulation can arise from the expectation that the reference application elements will perform their expected functions to achieve their expected results when combined for their commonly known purpose. See MPEP 2144.07.
The reference application does not teach the use of a pump system with the features of the instant claims.
SSED from the FDA teaches the MiniMed 670G system, which is used for insulin bolus doses for management of Type I diabetes mellitus (see e.g. page 1).
SSED teaches that the system can be programmed to automatically adjust delivery of basal insulin based on continuous glucose monitor sensor glucose values (see e.g. page 1).
SSED teaches that glucose is monitored by The Guardian Sensor (see e.g. page 2). The pump is compatible with paradigm reservoirs which can hold 3 mL volume reservoirs (see e.g. page 7).
SSED teaches that the system is a closed loop system (see e.g. page 2).
The instant specification indicates that the MiniMed 670G system is a traditional tethered pump is worn in a pocket or clipped to a belt and uses a fine tubing to connect the pump to the cannula. The pump body contains buttons that allow programming the insulin delivery at a slow, continuous (basal) rate as well as in supplemental (bolus) doses before meals or suspending the insulin infusion, if necessary (see instant specification page 4). The MiniMed pump can deliver insulin subcutaneously (see e.g. SSED page 3). The MiniMed system is automated, indicating that the device has a control for delivering dosing (see e.g. SSED page 69). Further, instant specification Example 9 indicates that the MiniMed system meets the limitations of the claims (see e.g. instant specification age 54).
It would have been obvious to one with ordinary skill in the art, at the time of the invention, to use a pump such as the MiniMed pump to deliver the formulation of the reference application because the Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The SSED document demonstrates the known use of pumps for continuous subcutaneous delivery of insulin. The MiniMed pump can be programmed to automatically calculate the insulin dose, based on information received from the CGM, to achieve glycemic control throughout the day and night. The MiniMed pump can deliver the formulation of the reference patent without alterations to components or functions. Further, the advantages of automatic adjustment of insulin delivery, and continuous glucose monitoring to identify correct insulin dosing provides motivation for one of skill in the art to use the MiniMed pump with the formulation of the reference application. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Applicant’s Arguments
Applicant argues:
1. Applicant has requested that the obviousness-type double patenting rejections be held in abeyance until the rejections are no longer provisional and the claims are otherwise deemed allowable.
Applicant’s arguments have been fully considered and are not persuasive for the following reasons:
Applicant is reminded that a request for a rejection to be held in abeyance does not “distinctly and specifically points out the supposed errors in the examiner’s action” as required under 37 CFR 1.111. See MPEP 714.02. Further, a rejection under double patenting precludes the identification of allowable subject matter. Applicant has not filed a terminal disclaimer, and the claims remain rejected for reasons set forth above.
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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).
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/ANDREA K MCCOLLUM/Examiner, Art Unit 1674
/BRIAN GANGLE/Primary Examiner, Art Unit 1645