DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rusch et al. (WO 2017/123840) in view of Ji et al. (WO 2011/119487).
Regarding claim 1, Rusch discloses
A pre-filled multi-dose injectable device (10, fig. 1 and pars. 0025-0030) comprising:
a stopper (100, fig. 1 and par. 0029);
a barrel (15, fig. 1 and pars. 0025-0026);
a solid lubricant (130, figs. 1-2 and par. 0029 for 130 being one or more fluoropolymer films which provide a low coefficient of friction. See also pars. 0031-0043 for the laminate payers 130) on at least one of the stopper and the barrel (see figs. 1-2 for 130 on the stopper 100), the pre-filled multi- dose injectable device being free or substantially free of a liquid lubricant (Examiner notes: see par. 0026 for barrel 15 of the device being formed of bare glass or other materials without any lubricants thereon, see par. 0029 for stopper 100 comprising one or more fluoropolymer films, not liquid lubricant. See also par. 0003 disclosing the problem with syringes comprising silicone lubricants causing inactivation or otherwise impact the efficacy of the pharmaceutical compositions and Rusch device solves that problem by using stoppers laminated with a fluoropolymer film); and
at least one formulated therapeutic (see par. 0019 for a pharmaceutical composition e.g., a drug, medicine or other therapeutic. See also pars. 0053-0060 for different therapeutic compounds/injectable drugs can be used in the device)
Rusch is silent about the at least one formulated therapeutic comprising: an active pharmacological agent; and at least one phenolic or benzyl alcohol preservative; wherein the at least one formulated therapeutic is free or substantially free of a surfactant and exhibits a turbidity increase of less than 30 nephelometric turbidity units (NTU) upon warming from 50C to 300C.
However, Ji teaches a syringe or other device being used for administration of the solution (page 38 lines 3-8) wherein the solution comprises at least one formulated therapeutic (page 2 lines 4-26 for antibody or protein or peptide in the compound) comprising: an active pharmacological agent (page 2 lines 4-26 for antibody or protein or peptide in the compound); and at least one phenolic or benzyl alcohol preservative (see page 28 lines 16-24 for preservatives including aromatic alcohols such as phenol or benzyl alcohol); wherein the at least one formulated therapeutic is free or substantially free of a surfactant (see page 1 lines 8-11 for Ji compounds being non-surfactant compounds).
Ji does not explicitly teach that the at least one formulated therapeutic exhibits a turbidity increase of less than 30 nephelometric turbidity units (NTU) upon warming from 50C to 300C. Ji only teaches turbidity resulting from aggregation is usually determined as a function of time by visual inspection or light scattering analysis (page 6 lines 19-28), not as a function of temperature. Ji teaches an example of measuring turbidity of 9 different vials at 250C at 0 hour, 4 hours, and 24 hours after the solutions are prepared and then sealed in the vials to allow to agitate at room temperature for a period of time (see page 39 line 10 to page 40 line 15 and see fig. 1). Ji also teaches turbidity being measured with different amount of protein aggregate present in solution at 0 hour, 4 hours, and 24 hours (see figs. 4 and 5). Therefore, Ji teaches the changes in turbidity of the solution being minimized and therefore, Ji solution is configured to exhibit a change in turbidity of less than 30 NTU upon warming from 50C to 300C.
It would have been obvious to one having ordinary skill in the art before the effective filling date of the claimed invention to modify Rusch device such that the device is used to deliver Ji solution to the patient, for the purpose of treating specific disorder of the patient (page 36 line 32 to page 38 line 2)
Regarding claim 2, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Ji further teaches wherein the active pharmacological agent comprises at least one of proteins, antibodies, cytokines, insulin, insulin analogs, growth hormones, growth factors, coagulation factors, proteases, kinases, phosphatases, vaccines, peptides, small interfering RNAs (siRNAs), small interfering DNAs (siDNAs), messenger RNAs (mRNAs), aptamers,orand/or a combination thereof (see page 2 lines 8-15 for the composition of matter comprising an antibody or other protein or peptide).
Regarding claim 3, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Ji further teaches wherein the at least one formulated therapeutic includes the active pharmacological agent at a concentration from about 1 mg/ml to about 200 mg/ml, from about 10 mg/ml to about 200 mg/ml, from about 20 mg/ml to about 200 mg/ml, from about 50 mg/ml to about 200 mg/ml, from about 80 mg/ml to about 200 mg/ml, from about 100 mg/ml to about 200 mg/ml, from about 120 mg/ml to about 200 mg/ml, or from about 150 mg/ml to about 200 mg/ml (see page 31 line 32 to page 32 line 12 for the concentration of the protein in the solution).
Regarding claim 4, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Ji further teaches wherein the surfactant comprises at least one of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, or a combination thereof (see page 1 lines 13-22 for polysorbates 20 and 80).
Regarding claim 5, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Ji further teaches wherein the at least one formulated therapeutic includes the surfactant at a concentration from 0 wt.% to about 0.1 wt.%, from 0 wt.% to about 0.075 wt.%, from 0 wt.% to about 0.05 wt.%, from 0 wt.% to about 0.025 wt.%, from 0 wt.% to about 0.01 wt.%, from 0 wt.% to about 0.005 wt.%, or from 0 wt.% to about 0.001 wt.% (see page 1 lines 8-11 and page 2 line 4 to page 4 line 18 for the composition of matter being free of surfactants. Therefore, the concentration of surfactants is 0 wt.%).
Regarding claim 6, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Ji further teaches wherein the at least one formulated therapeutic comprises a buffer having a pH from about 4.0 to about 9.5, from about 4.5 to about 9.0, from about 5.0 to about 8.5, from about 5.5 to about 8.0, from about 5.5 to about 7.5, from about 5.5 to about 7.0, or from about 5.5 to about 6.5 (see page 29 lines 23-30 for the pH-buffered solution at a pH from about 4-8 or about 5-7).
Regarding claim 7, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Ji further teaches wherein the at least one formulated therapeutic comprises a sugar having a concentration from 0 wt. % to about 15 wt.%, from about 0.1 wt.% to about 15 wt.%, from about 1 wt.% to about 15 wt.%, from about 1.5 wt.% to about 10 wt.%, from about 2 wt.% to about 10 wt.%, from about 3 wt.% to about 10 wt.%, or from about 5 wt.% to about 10 wt.% (see page 29 line 31 to page 30 line 11 for the concentration of sugars and sugar alcohols in the solution, see page 30 lines 12-18 for the molar ratio of protein to lyoprotectant wherein lyoprotectant includes sugar, see page 33 lines 21-28 for the amount of sugar in the liquid composition).
Regarding claim 8, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Ji further teaches wherein the at least one formulated therapeutic comprises a polyol having a concentration from 0 wt.% to about 5 wt.%, from about 0.1 wt.% to about 5 wt.%, from about 1 wt.% to about 5 wt.%, from about 1.5 wt.% to about 5 wt.%, from about 2 wt.% to about 5 wt.%, or from about 3 wt.% to about 5 wt.% (see page 27 lines 1-17 for polyol being a lyoprotectant or see page 27 line 22 to page 28 line 6 for polyol being a pharmaceutically acceptable sugar. See page 29 line 31 to page 30 line 11 for the concentration of sugars and sugar alcohols in the solution, see page 30 lines 12-18 for the molar ratio of protein to lyoprotectant wherein lyoprotectant includes sugar, see page 33 lines 21-28 for the amount of sugar in the liquid composition).
Regarding claim 9, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Ji further teaches wherein the at least one formulated therapeutic comprises an arginine salt having a concentration from 0 wt.% to about 5 wt.%, from about 0.1 wt.% to about 5 wt.%, from about 1 wt.% to about 5 wt.%, from about 1.5 wt.% to about 5 wt.%, from about 2 wt.% to about 5 wt.%, or from about 3 wt.% to about 5 wt.% (Examiner notes: see page 26 lines 13-26 for arginine being one of pharmaceutically-acceptable bases or see page 33 line 29 to page 34 line 9 for arginine being one of the additional excipients. See page 29 lines 23-30 for concentration of the bases in the solution).
Regarding claim 10, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Rusch further discloses wherein the stopper (100, fig. 1 and par. 0029) and the barrel (15, fig. 1 and pars. 0025-0026) are free or substantially free of the liquid lubricant silicone (Examiner notes: see par. 0026 for barrel 15 of the device being formed of bare glass or other materials without any lubricants thereon, see par. 0029 for stopper 100 comprising one or more fluoropolymer films, not liquid lubricant. See also par. 0003 disclosing the problem with syringes comprising silicone lubricants causing inactivation or otherwise impact the efficacy of the pharmaceutical compositions and Rusch device solves that problem by using stoppers laminated with a fluoropolymer film).
Regarding claim 11, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Rusch further discloses wherein the barrel (15, fig. 1 and pars. 0025-0026) is made of at least one of a glass material, a plastic material, a ceramic material, a metallic material, orand/or a combination thereof (see par. 0026 for 15 made of bare glass that is free or substantially free of silicone oil).
Regarding claim 12, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Ji further teaches wherein the turbidity increase is from 0 NTU to about 25 NTU, from 0 NTU to about 20 NTU, from 0 NTU to about 15 NTU, from 0 NTU to about 10 NTU, from 0 NTU to about 5 NTU, or from 0 NTU to about 1 NTU (Examiner notes: Ji does not explicitly teach that the at least one formulated therapeutic exhibits a turbidity increase as cited in claim 12. Ji only teaches turbidity resulting from aggregation is usually determined as a function of time by visual inspection or light scattering analysis (page 6 lines 19-28), not as a function of temperature. Ji teaches an example of measuring turbidity of 9 different vials at 250C at 0 hour, 4 hours, and 24 hours after the solutions are prepared and then sealed in the vials to allow to agitate at room temperature for a period of time (see page 39 line 10 to page 40 line 15 and see fig. 1). Ji also teaches turbidity being measured with different amount of protein aggregate present in solution at 0 hour, 4 hours, and 24 hours (see figs. 4 and 5). Therefore, Ji teaches the changes in turbidity of the solution being minimized and therefore, Ji solution is configured to exhibit a change in turbidity between 0 and 25 NTU).
Regarding claim 13, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Ji further teaches wherein the turbidity increase is no more than about 20 NTU, no more than about 10 NTU, no more than about 5 NTU, or no more than about 1 NTU (Examiner notes: Ji does not explicitly teach that the at least one formulated therapeutic exhibits a turbidity increase as cited in claim 13. Ji only teaches turbidity resulting from aggregation is usually determined as a function of time by visual inspection or light scattering analysis (page 6 lines 19-28), not as a function of temperature. Ji teaches an example of measuring turbidity of 9 different vials at 250C at 0 hour, 4 hours, and 24 hours after the solutions are prepared and then sealed in the vials to allow to agitate at room temperature for a period of time (see page 39 line 10 to page 40 line 15 and see fig. 1). Ji also teaches turbidity being measured with different amount of protein aggregate present in solution at 0 hour, 4 hours, and 24 hours (see figs. 4 and 5). Therefore, Ji teaches the changes in turbidity of the solution being minimized and therefore, Ji solution is configured to exhibit a change in turbidity no more than about 20 NTU).
Regarding claim 14, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Rusch further discloses wherein the solid lubricant is a low coefficient of friction layer (130, see fig. 1 and par. 0029) and the stopper comprises an elastomeric body (125, see fig. 1 and par. 0029) and the low coefficient of friction layer positioned on the elastomeric body (see fig. 1).
Regarding claim 15, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 14,
Rusch further discloses wherein the low coefficient of friction layer (130) comprises a fluoropolymer (see par. 0029).
Regarding claim 16, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 15,
Rusch further discloses wherein the fluoropolymer of the low coefficient of friction layer is an expanded fluoropolymer (see par. 0032).
Regarding claim 17, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 16,
Rusch further discloses wherein the elastomeric body (125) is at least partially imbibed into the expanded fluoropolymer of the low coefficient of friction layer (130, see fig. 2).
Regarding claim 18, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 16,
Rusch further discloses wherein the expanded fluoropolymer of the low coefficient of friction layer is pre-treated with at least one treatment of chemical etching, plasma treating, corona, and physical modification (see par. 0035).
Regarding claim 19, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 15,
Rusch further discloses wherein the fluoropolymer of the low coefficient of friction layer is an expanded polytetrafluoroethylene (ePTFE) (see pars. 0035-0036).
Regarding claim 20, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 15,
Rusch further discloses wherein the fluoropolymer of the low coefficient of friction layer comprises a composite fluoropolymer film (130, fig. 3 and par. 0036) having a barrier layer (145) and a porous layer (150), the barrier layer comprising at least one of polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), densified ePTFE, fluorinated ethylene propylene (FEP), ethylene tetrafluoroethylene (ETFE), polyvinylfluoride, polyvinylidene fluoride, perfluoropropylvinylether, perfluoroalkoxy polymers, polyethylene, polypropylene, poly (p-xylylene) (PPX), polylactic acid (PLA), poly(L-lactic acid) (PLLA), poly(D-lactic acid) (PDLA), and copolymers and combinations thereof (see par. 0036).
Regarding claim 21, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Rusch further discloses comprising a plunger rod (85, fig. 1 and par. 0029) movable in the barrel (15) and configured to move the stopper (100).
Regarding claim 22, Rusch in view of Ji discloses the pre-filled multi-dose injectable device of claim 1,
Ji further teaches wherein the at least one phenolic or benzyl alcohol preservative is selected from: a) a phenolic preservative comprising phenol, ortho-cresol, metacresol, para- cresol, propylparaben, methylparaben; b) a benzyl alcohol preservative comprising methylbenzyl alcohols; or c) any combination of the foregoing phenolic and benzyl alcohol preservatives (see page 28 lines 16-24).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. See PTO 892 form.
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/DUNG T ULSH/Examiner, Art Unit 3783