Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on February 27, 2026, has been entered.
Election/Restrictions
Applicant’s election without traverse of Group I (i.e., claims 1-4, 7-8, 13, 16-21, 23-31, 33-34, 36-40, 42-43, 45, 48-78, 80, and 87 directed to a medical infusion pump system) in the reply filed on March 25, 2024, is acknowledged. Additionally, Applicant’s election without traverse of Species A (i.e., as a composition comprising insulin aspart at a concentration of 10-1000 U/ml, ionic zinc at a concentration of 0.5-1% by weight of zinc based on the weight of insulin aspart in the composition, citrate as the zinc binding species at a concentration of 1 mM or more having a logK with respect to zinc ion binding in the range of 4.5-12.3 at 25°C, dodecyl maltoside as the alkyl glycoside at a concentration of 10-200 mcg/ml, NaCl as a charged tonicity modifying agent at a concentration of >60 mM that is a salt formed from between a Group I metal and a mono or divalent anion, the composition has a pH in the range of 5.5-9.0, phosphate as a buffer, m-cresol as a preservative, and the composition does not contain nicotinamide, nicotinic acid and/or trepostinil); and Species B (i.e., a medical infusion pump system comprises a glucose sensor as a controller, one or more reservoirs that contains an insulin compound, and at least one cannula or needle; the system delivers the composition in pulses; the system is a closed loop system and worn on the surface of the body) in the reply filed on March 25, 2024, is acknowledged.
Please note that Species A is expanded in light of the Examiner’s search to include where the insulin compound is insulin lispro or insulin glulisine, the tonicity modifying agent includes glycerol, the pH is in the range of 7.0-7.5 or 7.6-8.0, and the alkyl glycoside concentration species is 1-1000 µg/ml or 10-400 µg/ml.
Status of Claims
Claims 1-86 were originally filed on October 1, 2020.
The amendment received on October 1, 2020, canceled claims 5-6, 9-12, 14-15, 22, 32, 35, 41, 44, 46-47, 79, 81-82, and 85; amended claims 3, 8, 13, 16-18, 21, 23-25, 28-31, 33-34, 36, 37-40, 42-43, 45, 50, 55-66, 68-69, 71-78, 80, and 83. The amendment received on March 25, 2024, added new claim 87. The amendment received on December 30, 2024, canceled claims 5, 40, and 87; amended claims 1-4, 8, 13, 16, 18-21, 23-24, 28-31, 34, 36-37, 42, 48, 50, 70, and 75; and added new claim 88. The amendment received on February 27, 2026, canceled claims 33, 37, 55, and 88; and amended claims 1, 8, 13, 16, 18-19, 23, 30-31, 34, 36, 45, 49, and 51.
Claims 1-4, 8, 13, 16-21, 23-31, 34, 36, 38-39, 42-43, 45, 48-54, 56-78, 80, 83, and 86 are currently pending and claims 1-4, 8, 13, 16-21, 23, 25-31, 34, 36, 38-39, 42-43, 45, 48-51, 56-70, 72-75, 78, and 80 are under consideration as claims 83 and 86 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, and claims 24, 52-54, 71, and 76-77 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 March 25, 2024.
Priority
The present application claims status as a 371 (National Stage) of PCT/GB2019/050985 filed April 4, 2019, and claims priority under 119(a)-(d) to British Application Nos. 1805535.0 filed on April 4, 2018; and 1807321.3 filed May 3, 2018.
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d) for British Application Nos. 1805535.0 and 1807321.3, which papers have been placed of record in the file. Please note that the British applications are in English and therefore no further action is necessary.
Response to Arguments
Applicant’s arguments, see Response, filed 2/27/26, with respect to the 112(b) rejection have been fully considered and are persuasive. The rejection of claim 70 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 has been withdrawn.
Applicant’s arguments, see Response, filed 2/27/26, with respect to the 112(d) rejection have been fully considered and are persuasive. The rejection of claim 55 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 has been withdrawn.
Applicant’s arguments, see Response, filed 2/27/26, with respect to the 103(a) rejection have been fully considered and are persuasive. The rejection of claims 1-4, 8, 13, 16-21, 23, 25-31, 33-34, 36-39, 42-43, 45, 48-51, 55-57, 59-67, 72-74, and 80 as being unpatentable over Akers et al. US Publication No. 2017/0056478 A1 published on March 2, 2017 (cited in the IDS received on 10/22/20), in view of Pillion et al. WO 2011/094632 A1 published on August 4, 2011 (cited in the IDS received on 10/22/20), alone or as evidenced by, Veterinary Internal Medicine Nursing, “The ultimate guide to calculations: how to do medical maths easily,” Veterinary Internal Medicine Nursing, available online at www.veterinaryinternalmedicinenursing.com/blog/the-ultimate-guide-to-calculations#:~:text=%E2%81%A0To%20convert%20a%20%25%20solution,the%20concentration%20in%20mg%2Fml.&text=%E2%81%A0In%20general%2C%20you%20can,1%25%20is%2010mg%2Fml, 11 pages (accessed on 6/27/24) (hereinafter “the Veterinary Internal Medicine Nursing” reference) has been withdrawn. Please note that claim 1 being amended to exclude trepostinil in the composition overcomes this rejection.
Applicant’s arguments, see Response, filed 2/27/26, with respect to the 103(a) rejection have been fully considered and are persuasive. The rejection of claims 1, 58, 75, and 78 as being unpatentable over Akers et al. US Publication No. 2017/0056478 A1 published on March 2, 2017 (cited in the IDS received on 10/22/20), in view of Pillion et al. WO 2011/094632 A1 published on August 4, 2011 (cited in the IDS received on 10/22/20), alone or as evidenced by, Veterinary Internal Medicine Nursing, “The ultimate guide to calculations: how to do medical maths easily,” Veterinary Internal Medicine Nursing, available online at www.veterinaryinternalmedicinenursing.com/blog/the-ultimate-guide-to-calculations#:~:text=%E2%81%A0To%20convert%20a%20%25%20solution,the%20concentration%20in%20mg%2Fml.&text=%E2%81%A0In%20general%2C%20you%20can,1%25%20is%2010mg%2Fml, 11 pages (accessed on 6/27/24) (hereinafter “the Veterinary Internal Medicine Nursing” reference), and further in view of Pesach et al. US 2008/0281297 A1 published on November 13, 2008 has been withdrawn.
Applicant’s arguments, see Response, filed 2/27/26, with respect to the 103(a) rejection have been fully considered and are persuasive. The rejection of claims 1 and 68 as being unpatentable over Akers et al. US Publication No. 2017/0056478 A1 published on March 2, 2017 (cited in the IDS received on 10/22/20), in view of Pillion et al. WO 2011/094632 A1 published on August 4, 2011 (cited in the IDS received on 10/22/20), alone or as evidenced by, Veterinary Internal Medicine Nursing, “The ultimate guide to calculations: how to do medical maths easily,” Veterinary Internal Medicine Nursing, available online at www.veterinaryinternalmedicinenursing.com/blog/the-ultimate-guide-to-calculations#:~:text=%E2%81%A0To%20convert%20a%20%25%20solution,the%20concentration%20in%20mg%2Fml.&text=%E2%81%A0In%20general%2C%20you%20can,1%25%20is%2010mg%2Fml, 11 pages (accessed on 6/27/24) (hereinafter “the Veterinary Internal Medicine Nursing” reference), and further in view of Medtronic, “MiniMed™ Reservoirs,” Medtronic, available online at https://shop.medtronic-diabetes.co.uk/en/pumpsupplies/reservoirs/MiniMedreservoirs, 1 page (first available 2014) has been withdrawn.
Applicant’s arguments, see Response, filed 2/27/26, with respect to the 103(a) rejection have been fully considered and are persuasive. The rejection of claims 1 and 69-70 as being unpatentable over Akers et al. US Publication No. 2017/0056478 A1 published on March 2, 2017 (cited in the IDS received on 10/22/20), in view of Pillion et al. WO 2011/094632 A1 published on August 4, 2011 (cited in the IDS received on 10/22/20), alone or as evidenced by, Veterinary Internal Medicine Nursing, “The ultimate guide to calculations: how to do medical maths easily,” Veterinary Internal Medicine Nursing, available online at www.veterinaryinternalmedicinenursing.com/blog/the-ultimate-guide-to-calculations#:~:text=%E2%81%A0To%20convert%20a%20%25%20solution,the%20concentration%20in%20mg%2Fml.&text=%E2%81%A0In%20general%2C%20you%20can,1%25%20is%2010mg%2Fml, 11 pages (accessed on 6/27/24) (hereinafter “the Veterinary Internal Medicine Nursing” reference), and further in view of DiPerna et al. US Publication No. 2013/0053816 A1 published on February 28, 2013 has been withdrawn.
Applicant’s arguments, see Response, filed 2/27/26, with respect to the 103(a) rejection have been fully considered and are persuasive. The rejection of claims 1 and 88 as being unpatentable over Akers et al. US Publication No. 2016/0166695 A1 published on June 16, 2016 (cited in the IDS received on 10/22/20), in view of Pillion et al. WO 2011/094632 A1 published on August 4, 2011 (cited in the IDS received on 10/22/20), alone or as evidenced by, Veterinary Internal Medicine Nursing, “The ultimate guide to calculations: how to do medical maths easily,” Veterinary Internal Medicine Nursing, available online at www.veterinaryinternalmedicinenursing.com/blog/the-ultimate-guide-to-calculations#:~:text=%E2%81%A0To%20convert%20a%20%25%20solution,the%20concentration%20in%20mg%2Fml.&text=%E2%81%A0In%20general%2C%20you%20can,1%25%20is%2010mg%2Fml, 11 pages (accessed on 6/27/24) (hereinafter “the Veterinary Internal Medicine Nursing” reference) has been withdrawn.
Applicant’s arguments, see Response, filed 2/27/26, with respect to the 103(a) rejection have been fully considered and are persuasive. The rejection of claims 1-4, 8, 13, 16-21, 23, 25-31, 34, 36, 38-39, 42-43, 45, 48-51, 56-70, 72-75, 78, and 80 as being unpatentable over claims 1-2, 4, 7-9, 12-17, 19-20, 22-25, 33-36, 38-43, 45-46, 48, 51-78, 80, 83-84, and 86 of copending Application No. 17/044,729 (Jezek e al. US Publication No. 2021/0113763 A1) has been withdrawn. Please note that the rejection is withdrawn given that the ‘729 claimed invention requires an insulin concentration of 400-1000 U/ml, which is higher than the instant insulin concentration of 50-200 U/ml.
Applicant’s arguments, see Response, filed 2/27/26, with respect to the 103(a) rejection have been fully considered and are persuasive. The rejection of claims 1-4, 8, 13, 16-21, 23, 25-31, 33-34, 36-39, 42-43, 45, 48-51, 55-70, 72-75, 78, 80, and 88 as being unpatentable over claims 1, 7-9, 22-27, 31, 33-36, 39, 41-44, 46, 51, and 53-56 of copending Application No. 16/610,805 (Jezek e al. US Publication No. 2020/0093894 A1) in view of Akers et al. US Publication No. 2017/0056478 A1 published on March 2, 2017 (cited in the IDS received on 10/22/20), Pesach et al. US 2008/0281297 A1 published on November 13, 2008, Medtronic, “MiniMed™ Reservoirs,” Medtronic, available online at https://shop.medtronic-diabetes.co.uk/en/pumpsupplies/reservoirs/MiniMedreservoirs, 1 page (first available 2014), and DiPerna et al. US Publication No. 2013/0053816 A1 published on February 28, 2013 has been withdrawn. Please note that the rejection is withdrawn given that ‘805 has been abandoned.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
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 19, 34, and 36 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. Claims 19 and 34 are directed to where the sodium chloride is at a concentration of >120-300 mM. It is unclear what the concentration range of NaCl is, e.g., between 120-300 mM or >120 mM, or 121-300 mM. As such, the “>” symbol renders the scope of the concentration range unclear. An ordinary skilled artisan would be unable to ascertain the metes and bounds of the presently claimed invention with respect to the concentration range for NaCl.
Please note that the Examiner is interpreting the scope of claims 19 and 34 such that the concentration range of NaCl is 121-300 mM in order to advance prosecution. Also please note that claim 36 is rejected by virtue of its dependency.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 1-4, 8, 13, 16-21, 23, 25-31, 34, 36, 38-39, 42-43, 45, 48-51, 56-70, 72-75, 78 and 80 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. WO Publication No. 2012/174478 A2 published on December 20, 2012, in view of Pillion et al. WO 2011/094632 A1 published on August 4, 2011 (cited in the IDS received on 10/22/20), alone or as evidenced by, Veterinary Internal Medicine Nursing, “The ultimate guide to calculations: how to do medical maths easily,” Veterinary Internal Medicine Nursing, available online at www.veterinaryinternalmedicinenursing.com/blog/the-ultimate-guide-to-calculations#:~:text=%E2%81%A0To%20convert%20a%20%25%20solution,the%20concentration%20in%20mg%2Fml.&text=%E2%81%A0In%20general%2C%20you%20can,1%25%20is%2010mg%2Fml, 11 pages (accessed on 6/27/24) (hereinafter “the Veterinary Internal Medicine Nursing” reference), Knopp et al., J. Diabetes Sci. Technol. 13:597-600 (2019), and Hasim et al., Children 8:18 pages (2021).
For claims 1-4, 8, 13, 16, 18-19, 23, 25-31, 34, 36, 42-43, 45, 49, 51, and 72, with respect to an aqueous liquid pharmaceutical composition comprising (i) an insulin compound selected from insulin lispro, insulin glulisine, and insulin aspart, (ii) ionic zinc, (iii) an alkyl glycoside as a non-ionic surfactant at a concentration of 10-100 mcg/ml; (iv) citrate at a concentration of 10-30 mM; and (v) a tonicity modifying agent where the insulin compound is at a concentration of 50-200 U/ml and the tonicity modifying agent is NaCl at a concentration of 100-300 mM, and where the composition does not contain trepostinil as recited in instant claim 1; with respect to where the insulin compound is insulin glulisine as recited in instant claim 2; with respect to where the insulin compound is insulin lispro or insulin lispro as recited in instant claim 3; with respect to where the insulin compound is insulin lispro or insulin aspart as recited in instant claim 4; with respect to where the insulin compound is present at a concentration of 100-200 U/ml as recited in instant claim 8; with respect to where the ionic zinc is present at a concentration of 0.5-0.75% by weight of zinc based on the weight of insulin compound in the composition as recited in instant claim 13; with respect to where the citrate is at a concentration of 20-30 mM as recited in instant claim 16; with respect to where the insulin compound is insulin aspart, the citrate is at a concentration of 15-30 mM, and the alkyl glycoside is dodecyl maltoside as recited in instant claim 18; with respect to where the NaCl is at a concentration of 120-300 mM, and citrate is at a concentration of 20-30 mM as recited in instant claim 19; with respect to where the citrate is at a concentration of 20-30 mM as recited in instant claim 23; with respect to where alkyl glycoside is dodecyl maltoside as recited in instant claims 25-27; with respect to where the alkyl glycoside is present at a concentration of 20-100 µg/ml as recited in instant claim 28; with respect to where the alkyl glycoside is present at a concentration of 50 µg/ml as recited in instant claim 29; with respect to where the alkyl glycoside is present at a concentration of 20-100 mcg/ml as recited in instant claim 30; with respect to where the alkyl glycoside is present at a concentration of 50 mcg/ml as recited in instant claim 31; with respect to where NaCl is at a concentration of 120-300 mM as recited in instant claim 34; with respect to where the sodium chloride is present at a concentration of 150 mM as recited in instant claim 36; with respect to where the system comprises a phosphate buffer as recited in instant claim 42; with respect to where the composition further comprises a preservative such as m-cresol as recited in instant claim 43; with respect to where the composition further comprises nicotinamide as recited in instant claim 45; with respect to where the citrate is at a concentration of 20-30 mM as recited in instant claim 49; with respect to where the citrate is at a concentration of 30 mM as recited in instant claim 51; and with respect to where the system is a closed-loop system as recited in instant claim 72:
Yang et al. teaches an insulin pump comprising a stable co-formulation or composition comprising a pH between or about 6.8 to 7.8 or between 7.0 to 7.6, a therapeutically effective amount of a fast-acting insulin such as insulin lispro, insulin aspart, and insulin glulisine where the insulin is present in a concentration ranging from 10 U/ml to 1000 U/ml or 50 U/ml to 500 U/ml, a hyaluronan-degrading enzyme in an amount sufficient to render the composition super-fast acting, NaCl at a concentration between or about 50 mM to 200 mM or about 120-200 mM, an anti-microbially effective amount of a preservative or mixture of preservatives such as m-cresol, and one or more stabilizing agents such as an amino acid or derivative thereof, an amine, a sugar, a polyol, a salt or a surfactant (See Yang, pg. 3, last paragraph; pg. 4, last paragraph to pg. 5, 1st paragraph; pg. 10, 1st to last paragraph; pg. 12, 2nd paragraph; pg. 13, 2nd paragraph; pg. 21, 2nd paragraph; pg. 24, last paragraph; pg. 25, 3rd paragraph; pg. 67, 3rd paragraph; pg. 69, last paragraph; pg. 99, 2nd paragraph; pg. 100, 2nd and last paragraph; pg. 102, last paragraph; pg. 102, last paragraph to pg. 103, 1st and last paragraph; pg. 114, last paragraph to pg. 116, 2nd paragraph; pg. 120, last paragraph to pg. 121, 1st paragraph; pg. 122, 1st paragraph; pg. 122, last paragraph to pg. 123, 1st paragraph; pg. 125, last paragraph; pg. 130, 2nd paragraph to pg. 131, 1st paragraph; pg. 132, 2nd paragraph; pg. 136, 3rd paragraph; pg. 137, 1st and last paragraph; pg. 141, 1st paragraph; claims 1, 5, 26, 28, 33, 36, 39, 156). The surfactant is generally non-ionic such as polypropylene glycol, PEG, glycerin, sorbitol, poloxamer or polysorbate as a stabilizing agent is present in a % of mass concentration (w/v) in the formulation where the amount is between about 0.005% to 1.0% (See Yang, pg. 13, last paragraph to pg. 14, 1st paragraph; pg. 20, 3rd paragraph; pg. 100, last paragraph to pg. 101, 1st paragraph; pg. 137, 2nd to pg. 138, 2nd paragraph; claims 44-47). The stable co-formulation further comprises a sufficient amount of buffering agent such as citrate and phosphate to maintain the pH range of about 6.8 to 7.8 or about 6.5 to 7.5 (See Yang, pg. 5, 1st paragraph; pg. 11, 1st paragraph; pg. 21, last paragraph to pg. 22, 1st paragraph; pg. 69, last paragraph; pg. 99, 2nd to 3rd paragraph; pg. 122, 1st paragraph; pg. 133, 3rd to last paragraph; claims 4, 13, 29) where the buffering agent is present in a concentration between about 1 mM to 100 mM, or 10 mM to 50 mM, or 20 mM to 40 mM (See Yang, pg. 11, 1st paragraph; pg. 100, 2nd paragraph; pg. 134, 1st paragraph; claim 31). Yang et al. also teaches where the stable co-formulation comprises zinc at a concentration between about 0.001 to 0.1 mg per 100 units of insulin (mg/100U) (See Yang, pg. 15, 2nd paragraph; pg. 141, 1st paragraph; claims 56-57), further comprises a nicotinic compound such as nicotinamide (See Yang, pg. 15, 3rd paragraph; pg. 146, 2nd paragraph; claims 58-59). To avoid instability of the insulin and a hyaluronan-degrading enzyme, Yang et al. teaches that several parameters must be balanced to optimize compatibility in a co-formulation (See Yang, pg. 71, last paragraph). The required balance of preservatives, salt (e.g., NaCl), pH stabilizer(s), and/or buffer to retain acceptable levels of hyaluronan degrading enzyme activity and insulin solubility and activity (See Yang, pg. 71, last paragraph). Yang et al. found that conditions of high NaCl, e.g., 200 mM, and low pH, e.g., pH of 6.8, can be present in co-formulations of continuous subcutaneous infusion resulted in stable co-formulations at elevated temperatures (See Yang, pg. 118, 2nd paragraph; pg. 131, 2nd paragraph).
The stable co-formulation or composition can be formulated for delivery using a continuous subcutaneous insulin infusion containing a small infuser or pump (See Yang, pg. 19, 1st paragraph; pg. 45, 2nd paragraph; pg. 116, last paragraph; pg. 117, last paragraph; pg. 121, 1st paragraph; pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph; claim 152). Moreover, the stable co-formulation or composition can be formulated for delivery using a reservoir for a pump or a closed loop system (See Yang, pg. 18, last paragraph to pg. 19, 3rd paragraph; pg. 24, 1st paragraph; pg. 119, last paragraph; pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph; claim 151). Yang et al. defines a closed loop system as an integrated system for providing continuous glycemic control that contain a mechanism for measuring blood glucose, a mechanism for delivering one or more compositions including an insulin composition, and a mechanism for determining the amount of insulin needed to be delivered to achieve glycemic control (See Yang, pg. 36, last paragraph to pg. 37, 1st paragraph; pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph).
Thus, the teachings of Yang satisfies the claim limitations with respect to an infusion pump system comprising a pump and a reservoir comprising a composition comprising (i) an insulin compound selected from insulin lispro, insulin aspart, and insulin glulisine, (ii) ionic zinc, (iii) a surfactant, (iv) citrate as a buffer, and (v) NaCl thereby necessarily constituting a tonicity modifying agent as recited in instant claims 1-4 and 18; the claim limitation with respect to where the system comprises a phosphate buffer as recited in instant claim 42; the claim limitation with respect to where the composition further comprises a preservative such as m-cresol as recited in instant claim 43; the claim limitation with respect to where the composition further comprises nicotinamide as recited in instant claim 45; and the claim limitation with respect to where the system is an closed-loop system as recited in instant claim 72.
With respect to pharmaceutical composition being an aqueous liquid pharmaceutical composition, Yang et al. teaches that a liquid formulation can be kept for days, weeks, months or years prior to administration to a subject under varied temperatures (See Yang, pg. 43, 3rd paragraph). Yang et al. teaches that a composition refers to any mixture where it can be a solution, suspension, liquid, powder, paster, aqueous, non-aqueous or any combination thereof (See Yang, pg. 59, 4th paragraph). Fluid refers to any composition that can flow including aqueous mixtures (See Yang, pg. 61, 4th paragraph). In liquid form, the pharmaceutical preparations and be provided as a concentrated preparation to be diluted to a therapeutically effective concentration before use (See Yang, pg. 94, last paragraph; pg. 119, 3rd paragraph). Alternatively, the pharmaceutical preparations can be presented in lyophilized form for reconstitution with water before use (See Yang, pg. 95, 1st paragraph; pg. 119, 3rd paragraph). Moreover, Yang et al. teaches that the formulations can includes carriers such as diluents, adjuvants, excipients or vehicles with which the formulation is administered where such pharmaceutical carriers include sterile liquids such as water and oils (See Yang, pg. 105, 2nd paragraph; pg. 146, 3rd paragraph). Water is a typical carrier when the pharmaceutical composition is administered intravenously (See Yang, pg. 105, 2nd paragraph; pg. 146, 3rd paragraph). Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions (See Yang, pg. 105, 2nd paragraph; pg. 146, 3rd paragraph). Pharmaceutically acceptable carriers used in parenteral preparations include aqueous vehicles such as sterile water for injection and isotonic dextrose injection (See Yang, pg. 105, 3rd paragraph; pg. 146, last paragraph to pg. 147, 1st paragraph). Thus, the teachings of Yang et al. satisfy the claim limitation with respect to where the pharmaceutical composition is an aqueous liquid pharmaceutical composition as recited in instant claim 1.
With respect to the concentration of the insulin compound, as discussed supra, Yang et al. teaches that the concentration of the insulin compound is present in a concentration ranging from 10 U/ml to 1000 U/ml or 50 U/ml to 500 U/ml (See Yang, pg. 64, Table 2; pg. 123, 1st paragraph) thereby overlapping with the claimed insulin compound concentration range of 50-200 U/ml as recited in instant claim 1; and overlapping with the claimed insulin compound concentration ranges of 100-200 U/ml as recited in instant claim 8. MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses 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) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%". The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.) Moreover, the Federal Circuit found that a prima facie case existed where a claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms and the prior art taught that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." In re Geisler, 116 F.3d 1465, 1469-82, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). Therefore, the claimed insulin concentration range would have been obvious to one of ordinary skill in the art since the prior art insulin range (i.e., 10 U/ml to 1000 U/ml or 50 U/ml to 500 U/ml) overlaps with the claimed insulin concentration range (i.e., 50-200 U/ml as recited in instant claim 1; and 100-200 U/ml as recited in instant claim 8).
Additionally, and/or alternatively, the concentration of the insulin in the pharmaceutical composition is clearly a result specific parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal concentration of the insulin in the composition needed to achieve the desired results. Thus, an ordinary skilled artisan would have been motivated to adjust the concentration of the insulin in light of the teachings of Yang et al. because an ordinary skilled artisan would have been able to utilize the teachings of Yang et al. to obtain various concentration parameters with a reasonable expectation of success. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of the concentration of the insulin in the pharmaceutical composition would have been obvious at the time of applicant's invention. Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, because the combined teachings of the prior art are fairly suggestive of the claimed invention.
With respect to the ionic zinc concentration, as discussed supra, Yang et al. teaches where the stable co-formulation comprises, e.g., 0.005 mg/100U up to 0.1 mg/100U (See Yang, pg. 15, 2nd paragraph; pg. 141, 1st paragraph; claims 56-57). Yang et al. teaches where zinc ions are included in insulin formations, in particular, to insulin aspart formulations, to promote and stabilize hexamer formation (See Yang, pg. 65, last paragraph; pg. 111, last paragraph). As such, zinc is included in the co-formulations as a stabilizer for insulin hexamers (See Yang, pg. 141, 1st paragraph). Generally, it is known that 1U of insulin equates to 0.0347 mg of anhydrous insulin as evidenced by Knopp et al. (See Knopp, pg. 598, col. 1, 2nd paragraph; Table 1). As such, 100U of insulin equates to 3.47 mg. When calculating zinc as a % wt based on the wt of insulin, the % wt ranges from about 0.0288 wt% to about 2.88 wt% (i.e., (0.001/3.47) x 100 = 0.0288; and (0.1/3.47) x 100 = 2.88). Therefore, the ionic zinc wt% taught by Yang et al. overlaps with the instantly claimed zinc wt% range of 0.5-1 wt% as recited in instant claim 1, and 0.5-0.75 wt% as recited in instant claim 13.
MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses 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) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%". The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.) Moreover, the Federal Circuit found that a prima facie case existed where a claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms and the prior art taught that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." In re Geisler, 116 F.3d 1465, 1469-82, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). Therefore, the claimed zinc concentration range would have been obvious to one of ordinary skill in the art since the prior art zinc range (i.e., 0.0288 wt% to 2.88 wt%) overlaps with the claimed zinc concentration range (i.e., 0.5-1 wt% as recited in instant claim 1, and 0.5-0.75 wt% as recited in instant claim 13).
Additionally and/or alternatively, the wt% of the ionic zinc in the pharmaceutical composition is clearly a result specific parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal wt% of the ionic zinc in the composition needed to achieve the desired results. Thus, an ordinary skilled artisan would have been motivated to adjust the wt% of the ionic zinc in light of the teachings of Yang et al., for stabilizing a pharmaceutical insulin composition, because an ordinary skilled artisan would have been able to utilize the teachings of Yang et al. to obtain various concentration parameters with a reasonable expectation of success. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of the wt% of the ionic zinc in the pharmaceutical composition would have been obvious at the time of applicant's invention. Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, because the combined teachings of the prior art are fairly suggestive of the claimed invention.
With respect to where the pharmaceutical composition comprises an alkyl glycoside as a non-ionic surfactant such as dodecyl maltoside, as discussed supra, Yang et al. teaches that a surfactant can be included in the pharmaceutical composition. However, Yang et al. does not expressly teach that an alkyl glycoside is one of the surfactants to be included.
Pillion et al. teaches a pharmaceutical composition including at least one insulin analog and an absorption increasing amount of an alkyl glycoside (See Pillion specification, [0010], [0023]). Pillion et al. also teaches that the at least one insulin analog can be a fast acting insulin analog such as lispro, aspart and glulisine (See Pillion specification, [0023]), and alkyl glycoside has an alkyl chain including between 10 to 16 carbons such as dodecyl-β-d-maltoside and dodecyl-α-maltoside (See Pillion specification, [0010]-[0011], [0025]) thereby constituting where the alkyl glycoside is dodecyl maltoside (DDM) as recited in instant claims 25-27. The inclusion of an alkyl glycoside in the composition results in the composition exhibiting exemplary pharmacokinetic and pharmacodynamic profiles of the insulins in treatment of diseases such as diabetes (See Pillion specification, [0019]). More specifically, Pillion et al. teaches that DDM has been shown to stabilize protein formulations and increase their effective shelf-life thereby serving a dual role by acting as an absorption-enhancing agent and stabilizing the insulin compositions (See Pillion specification, [0077]). Therefore, the teachings of Pillion et al. suggest adding DDM as an alkyl glycoside, which necessarily constitutes a non-ionic surfactant given that it is a species of non-ionic surfactant, to a pharmaceutical composition comprising an insulin compound such as lispro, aspart or glulisine in order to stabilize the composition, increase the shelf-life of the composition, and enhance absorption of insulin into the patient’s blood. Thus, the teachings of Pillion et al. suggest the claim limitations with respect to where DDM is present as an alkyl glycoside as recited in instant claims 1, 18, and 25-27.
With respect to the concentration of the alkyl glycoside, as discussed supra, Yang et al. teaches that the pharmaceutical composition can comprise one or more stabilizing agents such as a surfactant (See Yang, claims 44-47). The surfactant is present in a % of mass concentration (w/v) in the formulation where the amount is between about 0.005% to 1.0% (See Yang, claims 44-47). However, Yang et al. does not expressly teach that the surfactant is an alkyl glycoside where the concentration unit in µg/ml.
As discussed supra for claim 1, Pillion et al. suggests adding an alkyl glycoside such as DDM to a pharmaceutical insulin composition in order to improve stability of the composition, increase the composition’s shelf-life, and increase absorption of the insulin into the patient’s blood once administered. Moreover, Pillion et al. exemplified 0.125% of an alkyl glycoside, e.g., as demonstrating superior properties (See Pillion specification, [0081]). At a concentration of 0.25% or 0.50% of the alkyl glycoside, slightly more insulin absorption was observed, but at a concentration of 0.06% less absorption was observed (See Pillion specification, [0072]) thereby suggesting that the alkyl glycoside concentration be above 0.06%. However, Pillion et al. examined nasal administration and not subcutaneous or continuous infusion administration (See Pillion specification, [0072]-[0073]). Moreover, Pillion et al. does not expressly teach the concentration unit in µg/ml.
The Veterinary Internal Medicine Nursing reference evidences that in general, you can add 1 decimal place to the percentage of the medication so every 1% is 10 mg/ml (See Veterinary Internal Medicine Nursing reference, pg. 3, 6th paragraph). As such, when converting the surfactant range taught by Yang et al. to µg/ml, the surfactant range would be 0.05 mg/ml to 10 mg/ml, which then is converted into 50 µg/ml to 10,000 µg/ml. With respect to the amounts of alkyl glycoside taught by Pillion et al., it is noted that 0.125% would equate to 1.25 mg/ml or 1250 µg/ml and 0.06% would equate to 0.6 mg/ml or 600 µg/ml.
It is noted that the concentration ranges taught by Pillion et al. lie within the large range taught by Yang et al. Thus, the concentration range taught by Yang overlaps with the instantly claimed concentration ranges as recited in instant claims 1 and 28-29. MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses 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) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%". The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.) Moreover, the Federal Circuit found that a prima facie case existed where a claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms and the prior art taught that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." In re Geisler, 116 F.3d 1465, 1469-82, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). Therefore, the claimed alkyl glycoside concentration range would have been obvious to one of ordinary skill in the art since the prior art surfactant range (i.e., 50 µg/ml to 10,000 µg/ml as taught by Akers) overlaps with the claimed alkyl glycoside concentration range (i.e., 10 µg/ml to 100 µg/ml as recited in instant claim 1; 20 µg/ml to 100 µg/ml as recited in instant claims 28 and 30; 50 µg/ml as recited in instant claims 29 and 31).
Additionally and/or alternatively, the concentration of the alky glycoside in the pharmaceutical composition is clearly a result specific parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal concentration of the alkyl glycoside in the composition needed to achieve the desired results. Thus, an ordinary skilled artisan would have been motivated to adjust the concentration of the alkyl glycoside in light of the teachings of Yang et al. and Pillion et al., for stabilizing a pharmaceutical insulin composition as a surfactant, because an ordinary skilled artisan would have been able to utilize the teachings of Yang et al. and Pillion et al.to obtain various concentration parameters with a reasonable expectation of success. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of the concentration of the alkyl glycoside in the pharmaceutical composition would have been obvious at the time of applicant's invention. Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, because the combined teachings of the prior art are fairly suggestive of the claimed invention.
With respect to the concentration of citrate, as discussed supra, the stable co-formulation further comprises a sufficient amount of buffering agent such as citrate and phosphate to maintain the pH range of about 6.8 to 7.8 or about 6.5 to 7.5 (See Yang, pg. 133, 3rd to last paragraph; claims 4, 13, 29) where the buffering agent is present in a concentration between about 1 mM to 100 mM, or 10 mM to 50 mM, or 20 mM to 40 mM (See Yang, pg. 134, 1st paragraph; claim 31).
Thus, the teachings of Yang et al. suggest a citrate concentration that overlaps with the claimed citrate concentration ranges as recited in instant claims 1, 16, 18-19, 23, 49, and 51. MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses 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) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%". The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.) Moreover, the Federal Circuit found that a prima facie case existed where a claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms and the prior art taught that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." In re Geisler, 116 F.3d 1465, 1469-82, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). Therefore, the claimed citrate concentration range would have been obvious to one of ordinary skill in the art since the prior art citrate range (i.e., about 1 mM to 100 mM, or 10 mM to 50 mM, or 20 mM to 40 mM) overlaps with the claimed citrate concentration range (i.e., 10-30 mM as recited in instant claim 1; 20-30 mM as recited in instant claim 16; 15-30 mM as recited in instant claim 18; 20-30 mM as recited in instant claim 19; 20-30 mM as recited in instant claim 23; 20-30 mM as recited in instant claim 49; and 30 mM as recited in instant claim 51).
Additionally and/or alternatively, the concentration of citrate in the pharmaceutical composition is clearly a result specific parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal concentration of the citrate in the composition needed to achieve the desired results. Thus, an ordinary skilled artisan would have been motivated to adjust the concentration of citrate in light of the teachings of Yang et al., because an ordinary skilled artisan would have been able to utilize the teachings of Yang et al. to obtain various concentration parameters with a reasonable expectation of success. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of the concentration of citrate in the pharmaceutical composition would have been obvious at the time of applicant's invention. Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, because the combined teachings of the prior art are fairly suggestive of the claimed invention.
With respect to the concentration of NaCl, as discussed supra, Yang et al. teaches that the composition contains NaCl at a concentration between or about 50 mM to 200 mM or about 120-200 mM (See Yang, pg. 102, last paragraph to pg. 103, 1st paragraph; pg. 121, last paragraph; pg. 130, last paragraph to pg. 131, 1st paragraph). Thus, the teachings of Yang et al. suggest a NaCl concentration that overlaps with the claimed NaCl concentration ranges as recited in instant claims 1, 19, 34, or 36. MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses 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) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%". The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.) Moreover, the Federal Circuit found that a prima facie case existed where a claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms and the prior art taught that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." In re Geisler, 116 F.3d 1465, 1469-82, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). Therefore, the claimed NaCl concentration range would have been obvious to one of ordinary skill in the art since the prior art NaCl range (i.e., about 50 mM to 200 mM or about 120-200 mM) overlaps with the claimed NaCl concentration range (i.e., 100-300 mM as recited in instant claim 1; 120-300 mM as recited in instant claims 19 and 34; and 150 mM as recited in instant claim 36).
Additionally and/or alternatively, the concentration of NaCl in the pharmaceutical composition is clearly a result specific parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal concentration of the NaCl in the composition needed to achieve the desired results. Thus, an ordinary skilled artisan would have been motivated to adjust the concentration of NaCl in light of the teachings of Yang et al., because an ordinary skilled artisan would have been able to utilize the teachings of Yang et al. to obtain various concentration parameters with a reasonable expectation of success. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of the concentration of NaCl in the pharmaceutical composition would have been obvious at the time of applicant's invention. Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, because the combined teachings of the prior art are fairly suggestive of the claimed invention.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the teachings of Yang et al. by substituting a surfactant with DDM at a concentration of 50 µg/ml to 10,000 µg/ml in an aqueous liquid pharmaceutical composition comprising insulin lispro, aspart, or glulisine as an insulin compound at a concentration of 50-500 U/ml, ionic zinc at a concentration of 0.0288 wt% to 2.88 wt%, citrate at a concentration of about 10-50 mM, and NaCl at a concentration of about 120-200 mM where the composition is contained in a medical infusion pump system in order to improve the stability of the composition, to increase the shelf-life of the composition, and to increase the absorption of the insulin into the patient’s blood once the composition is administered. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because pharmaceutical compositions comprising insulin and DDM as an alkyl glycoside were known to improve the stability of the composition, to increase the shelf-life of the composition, and to increase the absorption of the insulin into the patient’s blood once the composition is administered as taught by Pillion et al.
One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the aqueous liquid pharmaceutical composition of Yang et al. comprises insulin lispro, aspart, or glulisine as an insulin compound at a concentration of 50-500 U/ml, ionic zinc at a concentration of 0.0288 wt% to 2.88 wt%, citrate at a concentration of about 10-50 mM, NaCl at a concentration of about 120-200 mM, and a surfactant as a stabilizing agent at a concentration of about 50 mcg/ml to 10,000 mcg/ml where the composition is administered a patient via a medical infusion pump system. Therefore, substituting DDM as the surfactant in the aqueous liquid pharmaceutical composition would support the improvement of the composition’s stability, the increased composition’s shelf-life, and the increased absorption of the insulin the composition into the patient’s blood once administered via the pump of the system by constituting the simple substitution of one known element for another to obtain predictable results and/or some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant under KSR.
For claim 1, with respect to where the medical infusion pump system comprises a pump and a reservoir comprises a pharmaceutical composition for delivery by means of the pump to a mammal:
As discussed supra and below for claim 68, Yang et al. teaches that the stable co-formulation can be formulated for continuous subcutaneous insulin infusion (See Yang, pg. 3, 3rd paragraph; pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph). The stable co-formulations can be formulated for delivery using a vial, syringe, pen, reservoir for a pump or a closed loop system (See Yang, pg. 18, last paragraph; pg. 24, 1st paragraph; pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph). In a particular example, the stable co-formulations are formulated for delivery using a continuous subcutaneous insulin infusion that is provided by a closed loop system (See Yang, pg. 19, 1st paragraph; pg. 24, 1st paragraph; pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph). Thus, the teachings of Yang et al. satisfy the claim limitations with respect to an infusion pump system comprising a pump and a reservoir comprising the pharmaceutical composition for delivery by means of the pump as recited in instant claim 1.
However, the Examiner would like to remind Applicants that the preamble recites a medical infusion pump system, and while the use of a descriptive clause, i.e. “for the delivery …,” when referring to the contemplated use (i.e. “intended use”) of a claimed compound is proper, it is not a limitation and thus of no significance in determining the patentability thereof over the prior art, please refer to In re Thomas (CCPA 1949) 178 F2d 412, 84 USPQ 132. Therefore, the teachings of Yang et al. satisfy the intended use recited in instant claim 1.
For claims 17, 48, and 50, with respect to where the composition is substantially free of EDTA and any other zinc binding species having a logK with respect to zinc ion binding of more than 12.3 at 25°C:
Yang et al. teaches that the stable co-formulation contains an anti-microbially effective amount of a preservative or mixture of preservatives where the preservative can be phenol, m-cresol, EDTA, etc. (See Yang, pg. 25, 3rd paragraph). Although Yang et al. teaches that EDTA can be included in the co-formulation, Yang et al. does not require EDTA in the co-formulation. As such, the stable co-formulation taught by Yang would necessarily be substantially free of EDTA. Although Yang et al. teaches that the co-formulation can contain citrate and a preservative such as phenol or m-cresol, these agents encompassed in the instant composition. Thus, it would necessarily follow that there are no other zinc binding species including those having a logK with respect to zinc ion binding of more than 12.3 at 25°C.
Additionally and/or alternatively, MPEP 2112-2112.02 states that when a reference discloses all the limitations of a claim except for a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate or render obvious the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, Yang et al. teaches that the pharmaceutical composition contains citrate and a preservative such as phenol or m-cresol as a zinc binding species. Plus, Yang et al. does not require any chelating agents such as EDTA in the co-formulation.
The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not applicants’ pharmaceutical composition differs, and if so to what extent, from the pharmaceutical composition disclosed in Yang et al. The cited art taken as a whole demonstrates a reasonable probability that the pharmaceutical composition of Yang et al. is either identical or sufficiently similar to the claimed pharmaceutical composition that whatever differences exist are not patentably significant. Therefore, with the showing of the reference, the burden of establishing novelty or non-obviousness by objective evidence is shifted to the Applicants.
Merely because a function of a pharmaceutical composition is not expressly disclosed in a reference does not make the known pharmaceutical composition patentable. The new pharmaceutical compositions possess inherent functions which might not be displayed in the tests used in Yang et al. Accordingly, the disclosure of Yang et al. is a sufficient basis that the pharmaceutical composition is substantially free of EDTA and any other zinc binding species having a logK with respect to zinc ion binding of more than 12.3 at 25°C.
In the alternative, even if the claimed pharmaceutical composition is not identical to the Yang’s pharmaceutical composition with regard to some unidentified functions, the differences between that which is disclosed and that which is claimed are considered to be so slight that the Yang’s pharmaceutical composition is likely to necessarily possess the same functions of the claimed pharmaceutical composition particularly in view of the similar characteristics which they have been shown to share (i.e., containing citrate, and a preservative such as phenol or m-cresol with no added EDTA). Thus, the claimed pharmaceutical composition would have been obvious to those of ordinary skill in the art under the meaning of USC 103. Accordingly, the claimed invention as a whole was at least prima facie obvious, especially in the absence of sufficient, clear, and convincing evidence to the contrary. Thus, the teachings of Yang et al. satisfy the claim limitation with respect to where the composition is substantially free of EDTA and any other zinc binding species having a logK with respect to zinc ion binding of more than 12.3 at 25°C as recited in instant claims 17, 48, and 50.
For claim 20, with respect to where the source of the citrate is citric acid as recited in instant claim 20:
Yang et al. does not expressly teach that the source of the citrate is citric acid. However, the source or derivation of citrate constitutes a product-by-process limitation. Regarding product-by-process claims, the Federal Circuit has found that "[e]ven through product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim in the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." See MPEP 2113 and In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Furthermore, the Federal Circuit found that “[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes.” See MPEP 2113 and Amgen, Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340, 1370 n 14, 92 USPQ2d 1289, 1312, n 14 (Fed. Cir. 2009). In the instant case, the pharmaceutical composition in the system in claim 1 requires citrate, and thus, the source that citrate is obtained from or derived from is not a structural limitation of the claimed pharmaceutical composition. All that a prior art reference needs to show is the product of the process, i.e., citrate in this case. Thus, it is not necessary for Yang et al. to teach that the source of citrate is citric acid as such a limitation does not impart structure to the claimed pharmaceutical composition. Therefore, the teachings of Yang et al. satisfy the claim limitation as recited in instant claim 20.
For claim 21, with respect to where the molar ratio of ionic zinc to citrate is 1:3 to 1:175:
As discussed supra, Yang et al. teaches where the stable co-formulation comprises zinc at a concentration between about 0.001 to 0.1 mg per 100 units of insulin (mg/100U), e.g., 0.005 mg/100U up to 0.1 mg/100U (See Yang, pg. 15, 2nd paragraph; pg. 141, 1st paragraph; claims 56-57). As such, converting the concentration of zinc to molarity, the zinc concentration ranges from 0.0153 mM (i.e., zinc: 0.001 mg = 0.000001 g; MW of zinc = 65.38 g/mol; zinc molarity is 0.000001/65.38 =1.53 x 10-8 mol x 1000 = 1.53 x 10-5 mmol; assuming 100U is in 1 ml or 0.001 L, then (1.53 x 10-5)/0.001 = about 0.0153 mM) to 1.53 mM (same calculation but zinc is converted to 0.0001 g). Moreover, Yang et al. teaches that the stable co-formulation further comprises a sufficient amount of buffering agent such as citrate and phosphate to maintain the pH range of about 6.8 to 7.8 or about 6.5 to 7.5 (See Yang, pg. 133, 3rd to last paragraph; claims 4, 13, 29) where the buffering agent is present in a concentration between about 1 mM to 100 mM, or 10 mM to 50 mM, or 20 mM to 40 mM (See Yang, pg. 134, 1st paragraph; claim 31). Thus, the molar ratio of zinc to citrate equates to (0.0153 mM to 1.53 mM) of zinc to (10 mM to 50 mM) of citrate, or a range of about 1:6.54 (i.e., 10/1.53) to about 1:3268 (i.e., 50/0.0153). Thus, the molar ratio taught by Yang et al. overlaps with the instantly claimed molar ratio range between ionic zinc and citrate as claimed in instant claim 21. MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses 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) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%". The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.) Moreover, the Federal Circuit found that a prima facie case existed where a claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms and the prior art taught that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." In re Geisler, 116 F.3d 1465, 1469-82, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). Therefore, the claimed molar ratio range between ionic zinc and citrate would have been obvious to one of ordinary skill in the art since the prior art molar ratio range (i.e., about 1:6.54 (i.e., 10/1.53) to about 1:3268 (i.e., 50/0.0153)) overlaps with the claimed molar ratio range (i.e., 1:3 to 1:175).
For claim 38, with respect to where the composition is substantially isotonic:
Yang et al. teaches that the co-formulations can include a tonicity modifier such as NaCl to produce a solution with a desired osmolarity (See Yang, pg. 139, 3rd paragraph). The co-formulations have an osmolarity of between about 245 mOsm/kg to 305 mOsm/kg with a specific embodiment of 275 mOsm/kg (See Yang, pg. 139, 3rd paragraph). As evidenced by Hasim et al., the osmolality of an isotonic solution is equal to or close to that of plasma (275–295 mOsm/kg) (See Hasim, pg. 2, 2nd paragraph). As such, the osmolarity taught by Yang et al. correlates to where the stable insulin co-formulation is substantially isotonic. Thus, the teachings of Yang et al. satisfy the claim limitation as recited in instant claim 38.
For claim 39, with respect to where the pH of the composition is in the range of 5.5 to 9.0:
Yang et al. teaches that the pH of the composition is or about between 6.5 to 7.8, or 6.8 to 7.8, or 6.8 to 7.2 (See Yang, pg. 99, 2nd paragraph; pg. 122, 1st paragraph; pg. 132, 2nd paragraph; claim 153). Thus, the teachings of Yang satisfy the claim limitation with respect to the pH which lies inside the claimed pH range as recited in instant claim 39. MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses 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) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%". The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.) Moreover, the Federal Circuit found that a prima facie case existed where a claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms and the prior art taught that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." In re Geisler, 116 F.3d 1465, 1469-82, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). Therefore, the claimed pH range of the composition would have been obvious to one of ordinary skill in the art since the claimed range (i.e., 5.5 to 9.0 as recited in instant claim 39) overlaps with the prior art pH range of the composition (i.e., about 6.8 to about 7.2).
For claims 56-57, with respect to where the absorption of insulin compound into the blood stream of the mammal after administration using the system is bioequivalent to a standard composition com6rising the insulin compound at a concentration of 100 U/ml as recited in instant claim 56; and with respect to where the glycose reduction response caused by administration of a given amount of insulin compound to the mammal using the system is bioequivalent to a standard composition comprising the insulin compound at a concentration of 100 U/ml as recited in instant claim 57:
Yang et al. teaches that insulin activity can be assessed using methods and assays known in the art (See Yang, pg. 191, last paragraph). For example, the ability of an insulin, including insulin compositions and co-formulations, to act as a therapeutic agent can be assessed in vitro and in vivo (See Yang, pg. 191, last paragraph). The ability of insulin to stimulate glucose uptake or effect any other of its typical metabolic outcomes can be assessed in vitro (See Yang, pg. 192, 2nd paragraph). To measure insulin-stimulated glucose uptake, adipocytes are incubated with labeled glucose such as a radiolabel (See Yang, pg. 192, 2nd paragraph). The incorporated radioactivity is then measured to determine the amount of glucose uptake in the presence or absence of insulin (See Yang, pg. 192, 2nd paragraph). In vivo studies using diabetic or healthy animal models or human subjects can be performed to assess the therapeutic activity of insulin including insulin compositions and co-formulations (See Yang, pg. 192, 3rd paragraph). Insulin can be administered to animal models of diabetes to assess the effects on blood glucose levels, circulating insulin levels, and HbA1c (See Yang, pg. 192, 3rd paragraph). As such, Yang et al. teaches tests in order to determine the glucose reduction response of the suggested co-formulation of Yang in view of Pillon. However, Yang does not compare the glucose reduction response relative to a standard insulin composition. Furthermore, as discussed supra for claim 1, Pillion et al. demonstrates that insulin absorption is increased with the inclusion of an alkyl glycoside. However, Pillion et al. does not compare the insulin absorption relative to a standard insulin composition.
Additionally and/or alternatively, MPEP 2112-2112.02 states that when a reference discloses all the limitations of a claim except for a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate or render obvious the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, Yang et al. teaches tests including assays in order to evaluate and determine the glucose reduction response. Plus, Pillion et al. examined and found that when an alkyl glycoside is added to an insulin compound, insulin absorption is increased.
The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not the applicants’ pharmaceutical composition differs, and if so to what extent, from the pharmaceutical composition disclosed in Yang et al. and Pillion et al. The cited art taken as a whole demonstrates a reasonable probability that the pharmaceutical composition of Yang et al. and/or Pillion et al. is either identical or sufficiently similar to the claimed the pharmaceutical composition that whatever differences exist are not patentably significant. Therefore, with the showing of the reference, the burden of establishing novelty or non-obviousness by objective evidence is shifted to the Applicants.
Merely because a function of a pharmaceutical composition is not expressly disclosed in a reference does not make the known pharmaceutical composition patentable. The new pharmaceutical compositions possess inherent functions which might not be displayed in the tests used in Yang et al. and Pillion et al. Accordingly, the disclosures of Yang et al. and Pillion et al. are a sufficient basis that the pharmaceutical composition exhibits the bioequivalent properties recited in instant claims 56-57.
In the alternative, even if the pharmaceutical composition is not identical to Yang’s and/or Pillion’s pharmaceutical composition with regard to some unidentified functions, the differences between that which is disclosed and that which is claimed are considered to be so slight that Yang’s and/or Pillion’s pharmaceutical composition is likely to necessarily possess the same functions of the claimed pharmaceutical composition particularly in view of the similar characteristics which they have been shown to share. Thus, the ionic strength of the claimed pharmaceutical composition would have been obvious to those of ordinary skill in the art under the meaning of USC 103. Accordingly, the claimed invention as a whole was at least prima facie obvious, especially in the absence of sufficient, clear, and convincing evidence to the contrary. Thus, the teachings of Yang et al. and Pillion e al. satisfy the claim limitation with respect to the functional properties as recited in instant claims 56-57.
For claims 58 and 78, with respect to where the system comprises a controller for controlling the dose and frequency of administration of composition to the mammal as recited in instant claim 58; and with respect to where the system further comprises a glucose sensor and control means to direct the pump to deliver a dose of insulin compound based on information received from the glucose sensor as recited in instant claim 78:
As discussed supra, Yang et al. defines a closed loop system as an integrated system for providing continuous glycemic control that contain a mechanism for measuring blood glucose, a mechanism for delivering one or more compositions including an insulin composition, and a mechanism for determining the amount of insulin needed to be delivered to achieve glycemic control (See Yang, pg. 36, last paragraph to pg. 37, 1st paragraph; pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph). Typically, closed loop systems contain a glucose sensor, an insulin delivery device such as an insulin pump, and a controller that receives information from the glucose sensor and provides commands to the insulin delivery device (See Yang, pg. 37, 1st paragraph; pg. 168, 1st paragraph; pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph). The commands can be generated by software in the controller (See Yang, pg. 37, 1st paragraph; pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph). The software typically includes an algorithm to determine the amount of insulin required to be delivered to achieve glycemic control based upon the blood glucose levels detected by the glucose sensor or anticipated by the user (See Yang, pg. 37, 1st paragraph; pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph). Thus, the teachings of Yang et al. satisfy the claim limitations as recited in instant claims 58 and 78.
However, it is unnecessary for Yang et al. to teach the limitations with respect to where the controller is for controlling the dose and frequency of administration of the composition to a mammal as recited in instant claim 58 and a controller (i.e., control means) to direct the pump to deliver a dose of insulin compound based on information received from the glucose sensor as recited in claim 78 because the intended uses of the controller and/or glucose sensor in the medical infusion pump system do not state a condition that is material to patentability or provide a structural limitation that would further limit the claimed medical infusion pump system. The court has found that the determination of whether clauses such as “wherein” and “whereby" is a limitation in a claim is dependent on the specific facts of the case. If the “wherein" or “whereby” clause limits a process claim where the clause gives meaning and purpose to the manipulative steps, it should be given patentable weight. However, the court also found (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” In the instant case, claims 58 and 78 require the structure a controller and a glucose sensor, but the intended uses of the controller and/or glucose sensor in the medical infusion pump system (i.e., controlling the dose and frequency of administration of the composition to a mammal; and/or to direct the pump to deliver a dose of insulin compound based on information received from the glucose sensor) are intended results of the claimed controller and/or glucose sensor in the medical infusion pump system that gives little meaning and purpose to the structure of the claimed controller and/or glucose sensor in the medical infusion pump system. Accordingly, claims 58 and 78 recite an intended result that does not render material to patentability to the claimed medical infusion pump system.
For claims 59-67, 73-74, and 80, with respect to where the pump delivers the insulin compound in the composition to the mammal at a set basal rate which is 0.1-20 U/hr as recited in instant claim 59; with respect to where the pump delivers the composition in pulses as recited in instant claim 60; with respect to where the pulses have a pulse volume of 0.001-1 µL as recited in instant claim 61; with respect to where each pulse delivers 0.001-1 U insulin compound as recited in instant claim 62; with respect to where each pulse delivers 0.05-50 ng alkyl glycoside as recited in instant claim 63; with respect to where the ratio between the dose of insulin compound delivered (U) and the pulse volume (µL) is at least 0.4:1 as recited in instant claim 64; with respect to where the pump delivers 10-1000 pulses per hour as recited in instant claim 65; with respect to where the pump delivers the insulin compound in the composition to the mammal in a bolus dose as recited in instant claim 66; with respect to where the bolus dose is 1-100 U as recited in instant claim 67; with respect to where the system is worn on the surface of the body as recited in instant claim 73; with respect to where the system is worn on the surface of the body for 1 day or more as recited in instant claim 74; and with respect to where the system administers the composition subcutaneously to the mammal as recited in instant claim 80:
Yang et al. teaches that the stable co-formulation can be formulated for continuous subcutaneous insulin infusion (CSII) (See Yang, pg. 3, 3rd paragraph; pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph). As discussed supra and below for claim 68, the stable co-formulations can be formulated for delivery using a vial, syringe, pen, reservoir for a pump or a closed loop system (See Yang, pg. 18, last paragraph; pg. 24, 1st paragraph; pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph). In a particular example, the stable co-formulations are formulated for delivery using a continuous subcutaneous insulin infusion that is provided by a closed loop system (See Yang, pg. 19, 1st paragraph; pg. 24, 1st paragraph; pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph). Moreover, Yang et al. teaches that the CSII therapy is associated with continuous infusion of formulations by a pump or other device that is worn outside and near to the body for 24 hours a day for 2 to 3 days (See Yang, pg. 154, 3rd paragraph). Thus, the teachings of Yang et al. satisfy where the insulin composition is part of an infusion pump system comprising a pump and a reservoir for subcutaneous administration and is worn on the surface of the body.
However, it is unnecessary for Yang et al. to teach the limitations recited in claims 59-67, 73-74, and 80 because the intended uses of the pump in the medical infusion pump system do not state a condition that is material to patentability or provide a structural limitation that would further limit the claimed medical infusion pump system. The court has found that the determination of whether clauses such as “wherein” and “whereby" is a limitation in a claim is dependent on the specific facts of the case. If the “wherein" or “whereby” clause limits a process claim where the clause gives meaning and purpose to the manipulative steps, it should be given patentable weight. However, the court also found (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” In the instant case, the intended uses of the pump in the medical infusion pump system (i.e., delivering the composition at a set basal rate or in a bolus dose; and/or the composition in pulses; and/or wearing the system on the surface of the body; and/or administering the composition subcutaneously to a mammal) is an intended result of the claimed pump in the medical infusion pump system that gives little meaning and purpose to the structure of the claimed pump in the medical infusion pump system. Accordingly, claims 59-67, 73-74, and 80 recite an intended result that does not render material to patentability to the claimed medical infusion pump system.
For claim 68, with respect to where the reservoir has a total of up to 3 ml:
Yang et al. teaches that the stable co-formulations can be formulated for multi-dose administration where the volume of the stable co-formulations can be between about 0.5 ml to 50 ml, 1 ml to 10 ml, or 3 ml to 10 ml (See Yang, pg. 18, last paragraph; pg. 24, 1st paragraph; pg. 95, 2nd paragraph; pg. 119, last paragraph). As discussed supra, the stable co-formulations can be formulated for delivery using a vial, syringe, pen, reservoir for a pump or a closed loop system (See Yang, pg. 18, last paragraph; pg. 24, 1st paragraph). In a particular example, the stable co-formulations are formulated for delivery using a continuous subcutaneous insulin infusion that is provided by a closed loop system (See Yang, pg. 19, 1st paragraph; pg. 24, 1st paragraph; pg. 167, last paragraph). Although Yang et al. teaches the volume is of the co-formulation and not the reservoir, since Yang et al. teaches that the co-formulation is formulated for multi-dose administration via a reservoir for a pump, it would necessarily follow that the volume of the co-formulation would correspond to the volume of a reservoir. Thus, the teachings of Yang et al. suggest the claim limitation with respect to where the reservoir has a total volume of up to 3 ml because the volume taught by Yang et al. overlaps with the claimed volume as recited in instant claim 68.
MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses 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) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%". The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.) Moreover, the Federal Circuit found that a prima facie case existed where a claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms and the prior art taught that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." In re Geisler, 116 F.3d 1465, 1469-82, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). Therefore, the claimed volume range of the reservoir would have been obvious to one of ordinary skill in the art since the claimed range (i.e., up to 3 ml as recited in instant claim 68) overlaps with the prior art volume range (i.e., between about 0.5 ml to 50 ml, 1 ml to 10 ml, or 3 ml to 10 ml).
For claims 69-70, with respect to where the system comprises one or more further reservoirs as recited in instant claim 69; and with respect to where the one or more further reservoirs comprise an aqueous liquid pharmaceutical composition comprising an insulin compound as an active ingredient as recited in instant claim 70:
As discussed supra, Yang et al. teaches in a particular example, the stable co-formulations are formulated for delivery using a continuous subcutaneous insulin infusion that is provided by a closed loop system (See Yang, pg. 19, 1st paragraph; pg. 24, 1st paragraph; pg. 167, last paragraph) pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph). The insulin delivery devices typically contain at least one disposable reservoir containing an insulin formulation, a pump (including any controls, software, processing modules and/or batteries) and a disposable infusion set including a cannula or needle for subcutaneous injection and a tube connecting the cannula or needle to the insulin reservoir (See Yang, pg. 167, last paragraph; pg. 168, 2nd paragraph). As such, Yang et al. teaches that the insulin delivery system can contain more than one reservoir (i.e., at least one) where each would contain an insulin formulation. Thus, the teachings of Yang et al. satisfy the claim limitations as recited instant claims 69-70.
For claim 75, with respect to where the system comprises at least one cannula or needle in fluid communication with the pump or the at least one reservoir for subcutaneously infusing the insulin compound into the mammal:
As discussed supra, Yang et al. teaches in a particular example, the stable co-formulations are formulated for delivery using a continuous subcutaneous insulin infusion that is provided by a closed loop system (See Yang, pg. 19, 1st paragraph; pg. 24, 1st paragraph; pg. 167, last paragraph) pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph. Moreover, Yang et al. teaches that the CSII therapy is associated with continuous infusion of formulations by a pump or other device that is worn outside and near to the body for 24 hours a day for 2 to 3 days (See Yang, pg. 154, 3rd paragraph). Yang et al. also teaches that the insulin formulation or co-formulation is injected through a needle into the abdominal wall or thigh, which injection can be controlled by a programmed pump so that the insulin formulation or co-formulation is infused continuously (See Yang, pg. 154, 3rd paragraph; pg. 167, last paragraph to pg. 169, 2nd paragraph; pg. 170, last paragraph to pg. 176, 1st paragraph). Thus, the teachings of Yang et al. satisfy the claim limitation where the system comprises a needle that is in fluid communication with the pump for subcutaneously infusing the insulin composition into a subject as recited in instant claim 75.
However, it is unnecessary for Yang et al. to teach the limitation recited in claim 75 because the intended use of the needle in fluid communication with the pump in the medical infusion pump system does not state a condition that is material to patentability or provide a structural limitation that would further limit the claimed medical infusion pump system. The court has found that the determination of whether clauses such as “wherein” and “whereby" is a limitation in a claim is dependent on the specific facts of the case. If the “wherein" or “whereby” clause limits a process claim where the clause gives meaning and purpose to the manipulative steps, it should be given patentable weight. However, the court also found (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” In the instant case, the intended use of the needle in fluid communication with the pump in the medical infusion pump system (i.e., subcutaneously infusing the insulin composition into the mammal) is an intended result of the claimed needle in fluid communication with the pump in the medical infusion pump system that gives little meaning and purpose to the structure of the claimed needle in fluid communication with the pump in the medical infusion pump system. Accordingly, claim 75 recites an intended result that does not render material to patentability to the claimed medical infusion pump system.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments with respect to claims 1-4, 8, 13, 16-21, 23, 25-31, 34, 36, 38-39, 42-43, 45, 48-51, 56-70, 72-75, 78 and 80 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. However, the Examiner will address any argument as it pertains to the new 103(a) rejection supra.
In response to Applicant’s argument, i.e., non-ionic surfactants are not predictably interchangeable in pharmaceutical compositions (See Applicant’s Response received on 2/27/26, pg. 16-18), it is found unpersuasive. It is noted that this argument is merely the argument of counsel and is unsupported by evidence or declarations of those skilled in the art. Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See M.P.E.P. § 2129 and § 2144.03 for a discussion of admissions as prior art. Counsel's arguments cannot take the place of objective evidence. In re Schulze, 145 USPQ 716 (CCPA 1965); In re Cole, 140 USPQ 230 (CCPA 1964); and especially In re Langer, 183 USPQ 288 (CCPA 1974). See M.P.E.P. § 716.01(c) for examples of attorney statements that are not evidence and that must be supported by an appropriate affidavit or declaration. In the instant case, as discussed in the rejection supra, both Yang and Pillion seek to improve the stability and pharmacokinetic properties of fast-acting insulin compositions. Simply because Yang does not expressly teach alkyl glycosides as non-ionic surfactants does not per se preclude a finding of obviousness, especially given that Pillon expressly demonstrates improved stability and pharmacokinetic properties of fast-acting insulin compositions. Applicants are invited to provide evidence to support the argument that an ordinary skilled artisan would not substitute the surfactant of Yang with the surfactant of Pillon without a reasonable expectation of success knowing that alkyl glycosides demonstrated improved stability and pharmacokinetic properties in fast-acting insulin compositions. Applicants are respectfully reminded that the standard for predictability is one of a reasonable expectation of success of not an absolute expectation of success. Pursuant to MPEP 2143.02(II), obviousness does not require absolute predictability, however, at least some degree of predictability is required. Evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness. In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976). Thus, without evidence to the contrary, the Examiner maintains that an ordinary skilled artisan would substitute an alkyl glycoside of Pillion as a non-ionic surfactant of Yang.
Moreover, as stated in the Action mailed on 3/31/25, Pillion teaches that the insulin composition can be administered via CSF administration route, which constitutes an injection. Applicants have not provided any evidence that alkyl glycosides would unexpectedly be added to parenteral insulin compositions. However, assuming arguendo that alkyl glycosides are not approved for parenteral formulations, it is noted that the fact that an alkyl glycoside has not been approved by the FDA, alone without additional evidence, does not per se correlate to nonobviousness. Utilizing such a rationale would arguably preclude any new inventions that have not already been approved from patent protection. Therefore, contrary to Applicant’s argument, irrespective of whether an alkyl glycoside has been approved for use in parenteral formulations, an ordinary skilled artisan would be motivated to substitute an alkyl glycoside as the surfactant in light of the advantageous properties found by Pillion in fast-acting insulin compositions.
Accordingly, the rejection of the claimed invention are maintained as Applicant’s argument is found unpersuasive.
Double Patenting
Applicant is advised that should claim 16 be found allowable, claim 23 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 8, 13, 16-21, 23, 25-31, 34, 36, 38-39, 42-43, 45, 48-51, 56-70, 72-75, 78, and 80 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-51 of US Patent No. 12,527,845 B2 (Gerring e al.) in view of Yang et al. WO Publication No. 2012/174478 A2 published on December 20, 2012.
‘845 claims:
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(See ‘845 claims 1, 7, 15-17, 26-27, 36, 38-39, 41, 44-45, and 51-52 thereby corresponding to issued claims 1, 5, 8-10, 18-19, 22-27, and 32-33, respectively). As such, the ‘845 claimed invention constitutes the instant medical pump system comprising a pump and a reservoir comprising the instant aqueous liquid pharmaceutical composition including the instant insulin compound at a concentration overlapping with the instant concentration range, ionic zinc at a concentration identical to the instant concentration, citrate as a zinc binding species at a concentration overlapping with the instant concentration range that is derived from citric acid, an alkyl glycoside at a concentration overlapping with the instant concentration range, NaCl as a charged tonicity modifier at a concentration identical to the instant concentration, at a pH that overlaps with the instantly claimed pH range, and where the molar ratio of ionic zinc to citrate is identical to the instantly claimed range as recited in instant claims 1-4, 8, 13, 16, 18-21, 23, 28-29, 30-31, 34, 36, 39, 42-43, 45, 49, and 51. ‘845 claims where the alkyl glycoside is dodecyl maltoside (See ‘845, claims 13-15) thereby satisfying instant claims 18 and 25-27. ‘845 claims where the concentration of EDTA present is less than 0.1 mM thereby constituting the instant limitation where the composition is substantially free of EDTA (note: instant definition is EDTA less than 0.1 mM at instant pg. 11) thereby satisfying the claim limitations as recited in instant claim 17, 48, and 50. ‘845 claims where the osmolarity of the formulation ranges from about 250-500 mOsM/L (See ‘845) thereby encompassing where the formulation is substantially isotonic as recited in instant claim 38. Thus, the ‘845 claimed invention renders obvious instant claims 1-4, 8, 13, 16, 17-21, 23, 25-29, 30-31, 34, 36, 38-39, 42-43, 45, and 48-51.
Although ‘845 does not claim the properties and/or intended uses as recited in instant claims 1, 56-57, 59-67, 73-74, and 80, these properties and/or intended uses are not structural limitations of the instant system, and thus, is of no significance to the patentability to the instantly claimed system. Moreover, given the ‘845 claimed formulation renders obvious the instant composition, it would necessarily follow that the ‘845 claimed formulation would exhibit the instantly claimed properties. Thus, the ‘845 claimed invention also renders obvious the properties and/or intended uses as recited in instant claims 1, 56-57, 59-67, 73-74, and 80.
With respect to instant claims 58, 68-70, 72, 75, and 78, please see discussion of Yang et al. supra. Given that ‘845 claims a medical device comprising a pump and reservoir, an ordinary skilled artisan would be motivated to include the device structures as recited in instant claims 58, 68-70, 72, 75, and 78 with a reasonable expectation of success because medical insulin infusion pump systems were well known to contain such structural components. Therefore, the ‘845 claimed invention is not patentably distinct from the instant invention.
Claims 1-4, 8, 13, 16-21, 23, 25-31, 34, 36, 38-39, 42-43, 45, 48-51, 56-70, 72-75, 78, and 80 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6, 10-12, 14-16, 25-26, 35-36, 38-41, 43, 47, 51, and 55-58 of copending Application No. 16/610,826 (US Publication No. 2020/0093895 A1) in view of Yang et al. WO Publication No. 2012/174478 A2 published on December 20, 2012.
‘826 claims:
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(See ‘826, claims 1-2, 6, 11-12, 35, 38-41, 43, and 55-56). As such, the ‘826 claimed invention constitutes the instant aqueous liquid pharmaceutical composition including the instant insulin compound at a concentration overlapping with the instant concentration range, ionic zinc at a concentration identical to the instant concentration, citrate as a zinc binding species at a concentration overlapping with the instant concentration range, an alkyl glycoside at a concentration overlapping with the instant concentration range, NaCl as a charged tonicity modifier at a concentration identical to the instant concentration, at a pH that overlaps with the instantly claimed pH range, where the composition is isotonic, and where the molar ratio of ionic zinc to citrate overlaps with the instantly claimed range as recited in instant claims 1-4, 8, 13, 16, 18-19, 21, 23, 28-29, 30-31, 34, 36, 38-39, 42-43, 45, 49, and 51. ‘826 claims where the alkyl glycoside is dodecyl maltoside (See ‘826, claims 15-16) thereby satisfying instant claims 18 and 25-27. ‘826 claims where the concentration of EDTA present is less than 0.3 mM thereby overlapping with the amount of EDTA encompassed by the instant composition (note: instant definition is EDTA less than 0.1 mM at instant pg. 11) thereby satisfying the claim limitations as recited in instant claim 17, 48, and 50. Thus, the ‘826 claimed invention renders obvious instant claims 1-4, 8, 13, 16, 17-21, 23, 25-29, 30-31, 34, 36, 38-39, 42-43, 45, and 48-51.
Although ‘826 does not claim the properties and/or intended uses as recited in instant claims 1, 56-57, 59-67, 73-74, and 80, these properties and/or intended uses are not structural limitations of the instant system, and thus, is of no significance to the patentability to the instantly claimed system. Moreover, given the ‘826 claimed formulation renders obvious the instant composition, it would necessarily follow that the ‘826 claimed formulation would exhibit the instantly claimed properties. Thus, the ‘826 claimed invention also renders obvious the properties and/or intended uses as recited in instant claims 1, 56-57, 59-67, 73-74, and 80.
With respect to the system limitations as recited in instant claims 1, 58, 68-70, 72, 75, and 78, please see discussion of Yang et al. supra. Thus, an ordinary skilled artisan would be motivated to administer the ‘826 claimed formulation in a medical infusion pump system including the device structures as recited in instant claims 1, 58, 68-70, 72, 75, and 78 with a reasonable expectation of success because medical insulin infusion pump systems were well known to contain such structural components. Therefore, the ‘826 claimed invention is not patentably distinct from the instant invention.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4, 8, 13, 16-21, 23, 25-31, 34, 36, 38-39, 42-43, 45, 48-51, 56-70, 72-75, 78, and 80 are provisionally rejected 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, 57, 68-71, and 73-74 of copending Application No. 17/916,504 (US Publication No. 2023/0181675 A1) in view of Yang et al. WO Publication No. 2012/174478 A2 published on December 20, 2012.
‘504 claims:
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(See ‘504, claims 1, 10-11, 13, 17-19, 22-23, 26, 34, 36, 40, 44-46, 48-49, and 51). As such, the ‘504 claimed invention constitutes the instant aqueous liquid pharmaceutical composition including the instant insulin compound at a concentration identical to the instant concentration range, ionic zinc at a concentration identical to the instant concentration, citrate as a zinc binding species at a concentration overlapping with the instant concentration range that is derived from citric acid, an alkyl glycoside at a concentration overlapping with the instant concentration range, NaCl as a charged tonicity modifier, at a pH that overlaps with the instantly claimed pH range, and where the molar ratio of ionic zinc to citrate identical to the instantly claimed range as recited in instant claims 1-4, 8, 13, 16, 18-19, 20-21, 23, 28-29, 30-31, 38-39, 42-43, 45, 49, and 51. ‘504 claims where the osmolarity of the formulation ranges from about 250-500 mOsM/L (See ‘504 claim 44) thereby encompassing where the formulation is substantially isotonic as recited in instant claim 38. ‘504 claims where the alkyl glycoside is dodecyl maltoside (See ‘504, claim 23 and 26) thereby satisfying instant claims 18 and 25-27. ‘504 claims where the concentration of a citrate binding species present is less than 0.1 mM such as EDTA thereby constituting being substantially free of EDTA (note: instant definition is EDTA less than 0.1 mM at instant pg. 11) thereby satisfying the claim limitations as recited in instant claim 17, 48, and 50. Thus, the ‘504 claimed invention renders obvious instant claims 1-4, 8, 13, 16, 17-21, 23, 25-29, 30-31, 38-39, 42-43, 45, and 48-51.
Although ‘504 does not claim the concentration at which NaCl is present as recited in instant claims 1, 19, 34, and 36 for the NaCl concentration, please see discussion of Yang et al. supra. Thus, an ordinary skilled artisan would be motivated with a reasonable expectation of success to include NaCl in the insulin composition at a concentration ranging from 100-300 mM given that stable insulin formulations were known to contain NaCl in such a concentration range as a stabilizer.
Although ‘504 does not claim the properties and/or intended uses as recited in instant claims 1, 56-57, 59-67, 73-74, and 80, these properties and/or intended uses are not structural limitations of the instant system, and thus, is of no significance to the patentability to the instantly claimed system. Moreover, given the ‘504 claimed formulation renders obvious the instant composition, it would necessarily follow that the ‘504 claimed formulation would exhibit the instantly claimed properties. Thus, the ‘504 claimed invention also renders obvious the properties and/or intended uses as recited in instant claims 1, 56-57, 59-67, 73-74, and 80.
With respect to the system limitations as recited in instant claims 1, 58, 68-70, 72, 75, and 78, please see discussion of Yang et al. supra. Thus, an ordinary skilled artisan would be motivated to administer the ‘504 claimed formulation in a medical infusion pump system including the device structures as recited in instant claims 1, 58, 68-70, 72, 75, and 78 with a reasonable expectation of success because medical insulin infusion pump systems were well known to contain such structural components. Therefore, the ‘504 claimed invention is not patentably distinct from the instant invention.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4, 8, 13, 16-21, 23, 25-31, 34, 36, 38-39, 42-43, 45, 48-51, 56-70, 72-75, 78, and 80 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 7, 11, 14-15, 17, 20-22, 24, 26, 32-35, 39, 44, 49-50, 70-71, 73, of copending Application No. 19/416,930 (US Publication No. 2026/0102473 A1) in view of Yang et al. WO Publication No. 2012/174478 A2 published on December 20, 2012.
‘930 claims:
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(See ‘930 claims 1, 3, 7, 11, 15, 17, 22, 24, 26, 34-35, 39, 44, and 50). As such, the ‘930 claimed invention constitutes the instant medical pump system comprising a pump and a reservoir comprising an aqueous liquid pharmaceutical composition including the instant insulin compound at a concentration overlapping with the instant concentration range, ionic zinc at a concentration identical to the instant concentration, citrate as a zinc binding species at a concentration overlapping with the instant concentration range, an alkyl glycoside at a concentration overlapping with the instant concentration range, NaCl as a charged tonicity modifier at a concentration overlapping with the instant concentration range, at a pH that overlaps with the instantly claimed pH range, where the composition is isotonic, and where the molar ratio of ionic zinc to citrate identical to the instantly claimed range as recited in instant claims 1-4, 8, 13, 16, 18-19, 20-21, 23, 28-29, 30-31, 38-39, 42-43, 45, 49, and 51. ‘930 claims where the alkyl glycoside is dodecyl maltoside (See ‘930, claim 21-22) thereby satisfying instant claims 18 and 25-27. ‘930 claims where the composition is substantially free of EDTA thereby satisfying the claim limitations as recited in instant claim 17, 48, and 50. Thus, the ‘930 claimed invention renders obvious instant claims 1-4, 8, 13, 16, 17-21, 23, 25-29, 30-31, 38-39, 42-43, 45, and 48-51.
Although ‘930 does not claim the properties and/or intended uses as recited in instant claims 1, 56-57, 59-67, 73-74, and 80, these properties and/or intended uses are not structural limitations of the instant system, and thus, is of no significance to the patentability to the instantly claimed system. Moreover, given the ‘930 claimed formulation renders obvious the instant composition, it would necessarily follow that the ‘930 claimed formulation would exhibit the instantly claimed properties. Thus, the ‘930 claimed invention also renders obvious the properties and/or intended uses as recited in instant claims 1, 56-57, 59-67, 73-74, and 80.
With respect to the system limitations as recited in instant claims 58, 68-70, 72, 75, and 78, please see discussion of Yang et al. supra. Thus, an ordinary skilled artisan would be motivated to administer the ‘930 claimed formulation in a medical infusion pump system including the device structures as recited in instant claims 58, 68-70, 72, 75, and 78 with a reasonable expectation of success because medical insulin infusion pump systems were well known to contain such structural components. Therefore, the ‘930 claimed invention is not patentably distinct from the instant invention.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant’s arguments with respect to claims 1-4, 8, 13, 16-21, 23, 25-31, 34, 36, 38-39, 42-43, 45, 48-51, 56-70, 72-75, 78, and 80 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THEA D' AMBROSIO whose telephone number is (571)270-1216. The examiner can normally be reached M-F 11:00 to 8:00 pm.
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654
Prosecution Insights