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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/19/25 has been entered.
Response to Amendment
Applicant amended claims 30, 41, and 52, and canceled claims 40 and 51. Claims 30, 32-33, 35-39, 41, 43-44, 46-50, 52, 54-55, and 57-62 are currently pending.
Response to Affidavit/Declaration
The Declaration under 37 CFR 1.132 filed 12/19/25 is insufficient to overcome the rejections of claims 30, 32-33, 37, 40-41, 43-44, 48, 51-52, 54-55, and 60-62 based upon 35 U.S.C. 103 as unpatentable over Mitidieri in view of Rakesh, in further view of Devouassoux, and in further view of Inoue as set forth in the last Office action because there is insufficient data for allowing one of ordinary skill in the art to determine a trend in the data that proves the allegation of unexpected stability properties of the formulation across a concentration range corresponding to the claimed “therapeutically effective amount”.
The Declaration presents stability data over time for antioxidant free formulations of 0.128 mg/ml or 0.064 mg/ml norepinephrine in 5% dextrose (¶6-10, Tables 1-4). The Declaration concludes that the 0.128 mg/ml norepinephrine formulation is not stable, and therefore not suitable as a therapeutic, and that the 0.064 mg/ml norepinephrine formulation is stable, and therefore is suitable as a therapeutic (¶11). Because the Cope Declaration only provides stability data for two concentrations, 0.064 mg/mL and 0.128 mg/mL, one of ordinary skill in the art would not necessarily be able to determine a trend in the data which would cause them to come to the conclusion that 0.128 mg/mL is the maximum concentration of a “therapeutically effective amount of a ready-to-use, stable norepinephrine formulation” in 5% dextrose as argued by applicant.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Response to Arguments
Applicant’s arguments, see pages 9-16 of Applicant’s Remarks, filed 12/19/25, with respect to the rejections of claims 30, 32-33, 35-41, 43-44, 46-52, 54-55, and 57-62 under 35 U.S.C. 103 as being unpatentable over Mitidieri in view of Rakesh, in further view of Devouassoux, and in further view of Inoue have been fully considered and are not persuasive. In light of the amendments to require that the dextrose has a concentration of about 5%, new grounds of rejection have been made as indicated below.
Applicant argues, see pages 9-10, that the phrase “therapeutically effective amount” “refers to an amount of a pharmaceutical formulation … which is sufficient to treat or mitigate a condition, for example, to control blood pressure of an individual in acute hypotensive states”, referencing ¶0039 of the present specification. However, based on the present specification, the scope of the phrase “therapeutically effective amount” is not just limited to amounts sufficient for treating or mitigating acute hypotensive states, as discussed in ¶0039 of the present specification, but it also includes amounts of formulation comprising norepinephrine sufficient to serve as an adjunct in treating conditions such as cardiac arrest and/or profound hypotension, as discussed in ¶0040 of the present specification.
Applicant further argues, see page 10, that the phrase “therapeutically effective amount” is known in the art as being administered with a specific low concentration needed for treating a patient having acute hypotension, referencing evidentiary references. While the provided evidentiary references do demonstrate that norepinephrine formulations provided to a patient in concentrations between 0.016 to 0.128 mg/mL are examples of therapeutically effective amounts, the scope of the phrase “therapeutically effective amount” is not limited to those specific concentrations. Any amount of formulation with a concentration capable of treating or mitigating acute hypotensive states or serving as an adjunct in treating conditions such as cardiac arrest and/or profound hypotension fits within the scope of the phrase “therapeutically effective amount” as defined in ¶0039-0040, even if it is outside of the range or examples defined in the evidentiary references provided by applicant.
Applicant further argues, see pages 10-14, that the Cope Declaration filed 12/19/25 demonstrates that the limitation “therapeutically effective amount of a ready-to-use, stable norepinephrine formulation” excludes higher concentrations of 0.128 mg/mL in 5% dextrose due to their instability. However, the Cope Declaration includes stability tests of 0.128 mg/mL norepinephrine in 5% dextrose at pHs of 3.7 and 3.9 (¶7-8, Table 1) and stability tests of 0.064 mg/mL norepinephrine in 5% dextrose at pHs of 3.4-3.9 (¶9-10, Tables 2-4). The Cope Declaration indicates that the lower concentration of 0.064 mg/mL norepinephrine in 5% dextrose was stable, while the higher concentration of 0.128 mg/mL norepinephrine in 5% dextrose was not stable (¶11). Because the Cope Declaration only provides stability data for two concentrations, 0.064 mg/mL and 0.128 mg/mL, one of ordinary skill in the art would not necessarily be able to determine a trend in the data which would cause them to come to the conclusion that 0.128 mg/mL is the maximum concentration of a “therapeutically effective amount of a ready-to-use, stable norepinephrine formulation” in 5% dextrose as argued by applicant. At most, from the data provided in the Cope Declaration, an artisan would be able to conclude that 0.128 mg/mL norepinephrine in 5% dextrose would not be stable, and would therefore not be a ”therapeutically effective amount of a ready-to-use, stable norepinephrine formulation”.
Applicant further argues, see pages 14-15, that the norepinephrine formulation in 5% dextrose but not sodium chloride demonstrates surprising stability features that are unexpected based on Mitidieri in view of Rakesh. Applicant argues that while Rakesh may teach embodiments in which dextrose and sodium chloride are used interchangeably in norepinephrine formulations, Rakesh teaches norepinephrine formulations which include an antioxidant, and that therefore the combined teachings of Mitidieri and Rakesh would not lead one of ordinary skill in the art to have an expectation of success that an antioxidant free norepinephrine formulation using dextrose to the exclusion of sodium chloride would be stable. However, Mitidieri teaches process conditions to control the dissolved oxygen level and pH of the formulation, which are used to prepare antioxidant free norepinephrine formulations with stability at least equal to that of formulations including antioxidants (Mitidieri: ¶0028 and 0038-0048). Because the process conditions taught by Mitidieri result in the stability of the low concentration norepinephrine formulation, one of ordinary skill in the art could have modified the formulation of Mitidieri to use any of the aqueous tonicity adjusting agents taught by Rakesh with a reasonable expectation that they would not affect the stability of the formulation, even in the absence of an antioxidant.
Applicant further argues, see pages 15-16, that the Cope Declaration demonstrates that low concentrations of 0.064 mg/mL norepinephrine in 5% dextrose showed unexpected stability that could not have been predicted based on the combined teachings of Mitidieri and Rakesh. However, Mitidieri discloses stable norepinephrine formulations with concentrations from 0.04 to 0.2 mg/mL (¶0097-0099), which includes concentrations below the concentration ceiling alleged by applicant. Furthermore, as discussed above, Mitidieri attributes the stability of the antioxidant free, low concentration norepinephrine formulations to specific process conditions used to prepare the formulations with controlled, low dissolved oxygen levels and a controlled pH (¶0028 and 0038-0048). Therefore, based on the combined teachings of Mitidieri and Rakesh, one of ordinary skill in the art would have a reasonable expectation that low concentration norepinephrine formulations with dextrose instead of sodium chloride would be stable due to controlling the dissolved oxygen levels and pH, even at or below the concentrations indicated by the Cope Declaration. Therefore, the stability properties at low concentrations of 0.064 mg/mL are not unexpected based on the teachings of at least Mitidieri and Rakesh with respect to the norepinephrine formulation.
Additionally, as discussed below, by storing the low concentration norepinephrine formulation suggested by Mitidieri in view of Rakesh and in further view of Rowe in a packaging system including an oxygen scavenger like the packaging system of the claimed method and suggested by Devouassoux, one of ordinary skill in the art would expect the stability of the stored formulation to be high due to the action of the oxygen scavenger further reducing the dissolved oxygen levels in the formulation (Devouassoux: ¶0060-0062) in a manner which is independent of the composition of the formulation.
Applicant’s arguments, see pages 16-18 of Applicant’s Remarks, with respect to the rejections of claims 35-36, 46-47, and 57-58 under 35 U.S.C. 103 as obvious over Mitidieri in view of Rakesh, in further view of Devouassoux, in further view of Inoue, and in further view of Babrowicz; of claims 38, 49, and 59 as obvious over Mitidieri in view of Rakesh, in further view of Devouassoux, in further view of Inoue, and in further view of Farmer; and of claims 39 and 50 as obvious over Mitidieri in view of Rakesh, in further view of Devouassoux, in further view of Inoue, and in further view of McDorman have been fully considered. As discussed above, in light of the amendments to the independent claims to require that the dextrose has a concentration of about 5%, new grounds of rejection have been made as indicated below.
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.
Claims 30, 32-33, 37, 40-41, 43-44, 48, 51-52, 54-55, and 60-62 are rejected under 35 U.S.C. 103 as being unpatentable over Mitidieri et al. (US 2017/0049720 A1) in view of Rakesh et al. (US 2016/0058715 A1), in further view of Rowe (“Dextrose” Handbook of Pharmaceutical Excipients 2009, pp. 222-225), in further view of Devouassoux et al. (US 2014/0262883 A1), and in further view of Inoue et al. (US 2001/0008686 A1).
Regarding claims 30, 41, and 52, Mitidieri discloses a method of treating hypotension in a subject in need thereof (¶0034-0036: “a method of treatment for restoring and/or keeping physiological pressure levels” includes treating hypotension), the method comprising: administering to a subject a therapeutically effective amount of the ready-to-use, stable norepinephrine formulation by intravenous infusion (¶0034-0036; please note, Mitidieri refers to noradrenaline, which is another name for norepinephrine), wherein the ready-to-use, stable norepinephrine formulation is not diluted prior to infusion (¶0033-0036: the norepinephrine solution has a low concentration making it injectable, and therefore ready-to-use without dilution), and wherein the subject has hypotension (¶0034-0035), wherein the ready-to-use, stable norepinephrine formulation retains at least about 90% of an initial activity as measured by an initial and a final amount of R-norepinephrine present in the formulation after storage for at least 120 days at 25°C (¶0063-0073, 0097-0099: the titer of noradrenaline remains above 90%, while the enantiomer, d-noradrenaline, concentration remains always lower than 10% after 6 months of storage at 25°C or 3 months at 40°C). With respect to claim 30, Mitidieri further discloses that the ready-to-use, stable norepinephrine formulation comprises norepinephrine (¶0063), and is free of an antioxidant (¶0063); wherein the norepinephrine is in the form of norepinephrine bitartrate monohydrate (¶0031). With respect to claim 41, Mitidieri further discloses that the ready-to-use, stable norepinephrine formulation consists essentially of norepinephrine (¶0063), optionally hydrochloric acid and/or sodium hydroxide as pH adjusters (¶0050), and is free of an antioxidant (¶0063); wherein the norepinephrine is in the form of norepinephrine bitartrate monohydrate (¶0031). With respect to claim 52, Mitidieri further discloses that the ready-to-use, stable norepinephrine formulation consists of norepinephrine (¶0063: sodium chloride as an excipient is optional), optionally hydrochloric acid and/or sodium hydroxide as pH adjusters (¶0050), and is free of an antioxidant (¶0063); wherein the norepinephrine is in the form of norepinephrine bitartrate monohydrate (¶0031).
Claims 30, 41, and 52 recite that the norepinephrine formulation has a pH between 3.5 and 3.9. The claimed pH range overlaps the pH range of 3.2 to 3.6 taught by Mitidieri to aid with avoiding racemization and oxidation of norepinephrine (¶0027-0029; ¶0050-0052). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Mitidieri so that the formulation has a pH between 3.5 and 3.9 in order to avoid racemization and oxidation of the norepinephrine as taught by Mitidieri. Please see MPEP §2144.05(I).
Mitidieri discloses the optional use of sodium chloride as an excipient, in contrast to the claimed invention’s use of about 5% dextrose and the exclusion of sodium chloride from the formulation. Mitidieri does not disclose the claimed elements of the packaged, sealed container system carrying the ready-to-use, stable norepinephrine formulation, or that the method includes obtaining a packaged, sealed container system. Furthermore, while Mitidieri discloses the intravenous infusion of a ready-to-use, stable norepinephrine formulation to restore or keep physiological pressure levels, and therefore discloses the treatment of hypotension, Mitidieri is silent with respect to acute hypotension in particular as claimed.
Rakesh teaches a ready-to-administer parenteral dosage form of norepinephrine (Abstract) comprising, among other things, an aqueous tonicity adjusting agent for adjusting the osmolality of the norepinephrine formulation (¶0018, lines 12-26). Rakesh teaches that the aqueous tonicity adjusting agent may be sodium chloride, potassium chloride, calcium chloride, mannitol, glycerol, sorbitol, propylene glycol, dextrose, sucrose, and mixtures thereof (¶0018, lines 13-26). Therefore, for the problem of adjusting the osmolality of the norepinephrine solution, Rakesh teaches a finite number of identified, predictable aqueous tonicity adjusting agents. One of ordinary skill in the art could have pursued any of these agents with a reasonable expectation of appropriately adjusting the tonicity of the norepinephrine formulation because Rakesh teaches embodiments in which they are interchangeably used (¶0035-0037). Furthermore, Mitidieri teaches process conditions to control the dissolved oxygen level and pH of the formulation, which are used to prepare antioxidant free norepinephrine formulations with stability at least equal to that of formulations including antioxidants (Mitidieri: ¶0028 and 0038-0048). Because the process conditions taught by Mitidieri result in the stability of the low concentration norepinephrine formulation, one of ordinary skill in the art could have modified the formulation of Mitidieri to use any of the aqueous tonicity adjusting agents taught by Rakesh with a reasonable expectation that they would not affect the stability of the formulation, even in the absence of an antioxidant. Rakesh further teaches that norepinephrine is useful for treating acute hypotension (¶0004). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method disclosed by Mitidieri so that the norepinephrine formulation is used to treat patients with acute hypotension and comprises dextrose and does not comprise sodium chloride. Please see MPEP §2143(I)(E).
Mitidieri in view of Rakesh are silent with respect to the dextrose concentration.
Rowe teaches that dextrose is widely used in pharmaceutical formulations as a tonicity adjusting agent (Pages 222-223: Section 7), that dextrose solutions of about 5% w/v are isosmotic with serum (Pages 223-224: Sections 10 and 17), and that the dextrose concentration should be limited to 5% to prevent local vein irritation following intravenous administration (Page 224: Section 14). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method suggested by Mitidieri in view of Rakesh so that the dextrose has a concentration of about 5% in order to prevent local vein irritation following intravenous administration as taught by Rowe.
Mitidieri in view of Rakesh and in further view of Rowe is silent with respect to the claimed packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation and the claimed elements thereof.
Devouassoux teaches a packaged, sealed container system (Figs. 1 and 2; ¶0003 and 0017-0018) which may be used for storage of a norepinephrine formulation (¶0008 and 0069-0073) comprising a primary container with the formulation inside it (Figs. 1a-d and 2, feat. 3; ¶0017-0018 and 0040-0046), a secondary container, which may be a bag or pouch, with the primary container inside it (¶0047-0054), and an oxygen scavenger in the secondary container (¶0055-0056) and in fluid communication with the contents of the primary container (¶0037-0038). Devouassoux teaches that such a packaging system with an oxygen scavenger advantageously allows the dissolved oxygen in the formulation to be reduced to extremely low levels (¶0060-0062) and maintained at extremely low levels for long periods of time (¶0063), which enables the long term storage of oxygen sensitive pharmaceuticals like norepinephrine (¶0003 and 0007-0008). Devouassoux further teaches that the primary container may be an intravenous bag (¶0040-0042). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the methods suggested by Mitidieri in view of Rakesh and in further view of Rowe so that it comprises obtaining a packaged, sealed container system for stable storage of a ready-to-use, stable, norepinephrine formulation, wherein the package, sealed container system comprises i) a primary container comprising the ready-to-use, stable norepinephrine formulation, wherein the primary container is an intravenous bag; ii) a secondary container, wherein the primary container is disposed between and enclosed by the secondary container; and iii) an oxygen scavenger enclosed by the secondary container and in fluid communication with the contents of the primary container in order to reduce the dissolved oxygen in the formulation to extremely low levels and maintain those low levels for long periods of time as taught by Devouassoux.
Devouassoux, and therefore Mitidieri in view of Rakesh, in further view of Rowe, and in further view of Devouassoux, teaches that the secondary container may be a bag or pouch, but is does not disclose the construction of the bag or pouch.
Inoue teaches a medical container packaging bag (Fig. 4, feat. B; ¶0060) comprising a first flexible sheet layer, a second flexible sheet layer, and a seal disposed along a common peripheral edge of the first and second flexible sheet layers (Fig. 4; ¶0057 and 0060) for enclosing a medical container (Fig. 4, feat. A1) for enclosing a medical container containing a medicinal (Fig. 4, feat. A1). Inoue further teaches that the base film (Fig. 4, feat. B1) of the packaging bag (B) has high gas barrier properties in order to prevent the degradation of the medicinal (¶0061-0062). As discussed above, Mitidieri in view of Rakesh, in further view of Rowe, and in further view of Devouassoux discloses the elements of claim 30, except for those pertaining to the structure of the secondary container, and Inoue teaches the structure of the secondary container. Therefore, the prior art includes each element claimed, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference. One of ordinary skill in the art could have combined the elements as claimed because Inoue teaches a secondary container with the claimed structure enclosing a medical container between its first and second flexible sheet layer (Fig. 4), and would have recognized that enclosing the primary container of Mitidieri in view of Rakesh, in further view of Rowe, and in further view of Devouassoux in a secondary container with the structure taught by Inoue would have the predictable results of preventing the degradation of the norepinephrine formulation because Devouassoux discloses that the secondary container should prevent oxygen ingress, i.e. the secondary container should have oxygen barrier properties (Devouassoux: ¶0047-0050) and Inoue teaches a secondary container with the claimed structure (Inoue: Fig. 4, feat. B) which has high gas barrier properties for preventing degradation (¶0061-0062). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method suggested by Mitidieri in view of Rakesh, in further view of Rowe, and in further view of Devouassoux so that the secondary container comprises a first flexible sheet layer, an opposing second flexible sheet layer, and a seal disposed along a common peripheral edge of the first and second sheet layer as taught by Inoue. Please see MPEP §2143(I)(A).
Regarding claims 32, 43, and 54, Mitidieri in view of Rakesh, in further view of Rowe, in further view of Devouassoux, and in further view of Inoue suggests the methods of claims 30, 41, and 52, respectively. Devouassoux further teaches that liquids degassed by nitrogen bubbling may have a residual oxygen level of up to approximately 400 ppb (¶0060), and that the oxygen scavenger may remove up to about 4000 ppb of oxygen per month from the liquid drug (¶0061) in order to establish and maintain a substantially oxygen free environment for at least 12 months (Fig. 9; ¶0063) such that the liquid drug is stable at 25°C for at least 12 months (¶0072). Therefore, Mitidieri in view of Rakesh, in further view of Rose, in further view of Devouassoux, and in further view of Inoue further suggests that the ready-to-use, stable norepinephrine formulation has a dissolved oxygen level of less than 0.5 ppm after storage for at least 150 days at 25°C.
Regarding claims 33, 44, and 55, Mitidieri in view of Rakesh, in further view of Rowe, in further view of Devouassoux, and in further view of Inoue suggests the methods of claims 30, 41, and 52, respectively. Devouassoux further teaches that liquids degassed by nitrogen bubbling may have a residual oxygen level of up to approximately 400 ppb (¶0060), and that the oxygen scavenger may remove up to about 4000 ppb of oxygen per month from the liquid drug (¶0061) in order to establish and maintain a substantially oxygen free environment for at least 12 months (Fig. 9; ¶0063) such that the liquid drug is stable at 25°C for at least 12 months (¶0072). Therefore, Mitidieri in view of Rakesh, in further view of Rose, in further view of Devouassoux, and in further view of Inoue further suggests that the ready-to-use, stable norepinephrine formulation has a dissolved oxygen level of less than 0.5 ppm after storage for at least 180 days at 25°C.
Regarding claims 37 and 48, Mitidieri in view of Rakesh, in further view of Rowe, in further view of Devouassoux, and in further view of Inoue suggests the methods of claims 30 and 41, respectively. Devouassoux further teaches that the secondary packaging may be made from coextruded films incorporating a metal foil to reduce the oxygen permeability (¶0048-0050). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the methods suggested by Mitidieri in view of Rakesh, in further view of Rowe, in further view of Devouassoux, and in further view of Inoue so that the first flexible sheet layer comprises a coextruded film including a metal foil to reduce the oxygen permeability of the secondary packaging as taught by Devouassoux.
Regarding claims 60-62, Mitidieri in view of Rakesh, in further view of Rowe, in further view of Devouassoux, and in further view of Inoue suggests the methods of claims 30, 41, and 52. As discussed above, Mitidieri teaches a pH range of 3.2 to 3.6 to aid with avoiding racemization and oxidation of norepinephrine (¶0027-0029; ¶0050-0052). The claimed pH range of 3.6 to 3.8 of claims 60-62 overlaps the prior art range taught by Mitidieri because both the claimed range and prior art range include a pH of 3.6. Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed inventions to modify the methods suggested by Mitidieri in view of Rakesh, in further view of Rowe, in further view of Devouassoux, and in further view of Inoue so that the ready-to-use, stable norepinephrine formulation has a pH of 3.6 to 3.8 in order to avoid racemization and oxidation of the norepinephrine as taught by Mitidieri. Please see MPEP §2144.05(I).
Claims 35-36, 46-47, and 57-58 are rejected under 35 U.S.C. 103 as being unpatentable over Mitidieri et al. (US 2017/0049720 A1) in view of Rakesh et al. (US 2016/0058715 A1), in further view of Rowe (“Dextrose” Handbook of Pharmaceutical Excipients 2009, pp. 222-225), in further view of Devouassoux et al. (US 2014/0262883 A1), in further view of Inoue et al. (US 2001/0008686 A1), and in further view of Babrowicz et al. (US 2010/0256590 A1).
Regarding claims 35, 46, and 57, Mitidieri in view of Rakesh, in further view of Rowe, in further view of Devouassoux, and in further view of Inoue suggests the methods of claims 30, 41, and 52, respectively. Devouassoux further teaches that the primary container may be an intravenous bag for intravenous administration (¶0040-0042), but is silent with respect to the intravenous bag having a single administration port.
Babrowicz teaches a multilayer film and medical solutions pouches formed therefrom (Abstract). Babrowicz teaches that the medical solution container (Fig. 2, feat. 30; ¶0057) may comprise a single port (60; ¶0059) which is attachable to a standard intravenous device and/or administration set, and may serve a dual role for introducing the medical solution into the container and then releasing it for administration to the patient at the desired time (¶0059). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the invention to modify the methods suggested by Mitidieri in view of Rakesh, in further view of Rowe, in further view of Devouassoux, and in further view of Inoue so that the primary container has a single port, the single port comprising an administration port for delivering the ready-to-use, stable norepinephrine formulation to a patient so that the primary container is attachable to standard intravenous devices and/or administration sets as taught by Babrowicz.
Regarding claims 36, 47, and 58, Mitidieri in view of Rakesh, in further view of Rowe, in further view of Devouassoux, and in further view of Inoue suggests the methods of claims 30, 41, and 52, respectively. Devouassoux teaches that the primary container may be an IV bag or pouch (¶0040-0042), but is silent with respect to the construction of the bag or pouch.
Babrowicz teaches a multilayer film and medical solutions pouches formed therefrom (Abstract). Babrowicz teaches a coextruded multilayer film (¶0055) comprising an inner polypropylene heat seal layer (Fig. 1, feat. 14; ¶0033) and an outer polyamide composite layer (Fig. 1, feat. 16; ¶0024-0029) which can be formed into a pouch by mating two films such that the heat seal layers are brought into contact and providing heat to the peripheral edges of the films (¶0033, 0057, and 0058). Babrowicz teaches that pouches made of such a film may be sterilized via autoclaving without the formation of foam in the solution held by the pouch (¶0018). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the methods suggested by Mitidieri in view of Rakesh, in further view of Rowe, in further view of Devouassoux, and in further view of Inoue so that the primary container is a plastic IV bag comprising a third flexible sheet layer, an opposing fourth flexible sheet layer, and a primary container seal disposed along a common peripheral edge of the third and fourth flexible sheet layers, and wherein the third and the fourth flexible sheet layers are coextruded film laminates comprising a polypropylene layer as taught by Babrowicz so that the primary container may be sterilized via autoclaving without the formation of foam in the norepinephrine solution.
Claims 38, 49, and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Mitidieri et al. (US 2017/0049720 A1) in view of Rakesh et al. (US 2016/0058715 A1), in further view of Rowe (“Dextrose” Handbook of Pharmaceutical Excipients 2009, pp. 222-225), in further view of Devouassoux et al. (US 2014/0262883 A1), in further view of Inoue et al. (US 2001/0008686 A1), and in further view of Farmer et al. (US 6,613,036 B1).
Regarding claims 38, 49, and 59, Mitidieri in view of Rakesh, in further view of Rowe, in further view of Devouassoux, and in further view of Inoue suggests the methods of claims 30, 41, and 52, respectively, but do not disclose that the opposing second flexible sheet layer comprises a transparent coextruded film configured to allow visual inspection into the secondary container, and is colored to protect the ready-to-use, stable norepinephrine formulation from light.
Farmer teaches a light protective container for a light-sensitive fluid including a container for the fluid (Fig. 1, feat. 12) and a colored sleeve (Fig. 1, feat. 14; Abstract). Farmer teaches that the sleeve substantially covers the container (Col. 5, lines 62 – Col. 6, line 5) and is made of a colored translucent material in order to allow for visual inspection of the container while protecting the contents from harmful light (Col. 7, lines 7-42). Farmer teaches that visual inspection can be used to ensure that the fluid is clean and free of particulates and precipitates (Col. 1, lines 15-32). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the methods suggested by Mitidieri in view of Rakesh, in further view of Rowe, in further view of Devouassoux, and in further view of Inoue so that the second opposing flexible sheet layer comprises a transparent coextruded film configured to allow visual inspection into the secondary container and is colored to protect the ready-to-use, stable norepinephrine formulation from light as taught by Farmer so that the norepinephrine formulation can be inspected for cleanliness and a lack of particulates while protecting it from undesirable photochemical degradation.
Claims 39 and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Mitidieri et al. (US 2017/0049720 A1) in view of Rakesh et al. (US 2016/0058715 A1), in further view of Rowe (“Dextrose” Handbook of Pharmaceutical Excipients 2009, pp. 222-225), in further view of Devouassoux et al. (US 2014/0262883 A1), in further view of Inoue et al. (US 2001/0008686 A1), and in further view of McDorman (US 2013/0327677 A1).
Regarding claims 39 and 50, Mitidieri in view of Rakesh, in further view of Rowe, in further view of Devouassoux, and in further view of Inoue suggests the methods of claims 30 and 41, respectively, but do not disclose the water transmission rate of any component of the secondary container.
McDorman teaches a packaging system for preserving a nonoxygenated hemoglobin based therapeutic agent (Abstract). McDorman teaches that protecting therapeutic agents against oxygen and moisture is important for preserving their therapeutic properties (¶0004 and 0005). McDorman teaches that the packaging system comprises a secondary overwrap for protecting the primary package (¶0009), and that the secondary overwrap has a water vapor transmission rate o f0.0007 g/100 in2/day (approximately 0.0124 g/m2/day). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the methods suggested by Mitidieri in view of Rakesh, in further view of Rowe, in further view of Devouassoux, and in further view of Inoue so that the second flexible sheet layer has a water transmission rate of less than 3.0 g/m2/day as taught by McDorman in order to maintain the therapeutic properties of the norepinephrine formulation.
Conclusion
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/ARJUNA P CHATRATHI/Examiner, Art Unit 3781
/SARAH AL HASHIMI/Supervisory Patent Examiner, Art Unit 3781