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 .
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 Arguments
Applicant’s arguments, see pages 10-18 of Applicant’s Remarks, filed 09/14/26, with respect to the rejections of claims 30, 32-33, 35-39, 41, 43-44, 48, 52, 54-55, and 60-62 under 35 U.S.C. 103 as unpatentable over Mitidieri in view of Rakesh, in further view of Rose, in further view of Devouassoux, and in further view of Inoue, of claims 35-36, 46-47, and 57-58 in further view of Babrowicz, of claims 38, 49, and 59 in further view of Farmer, and of claims 39 and 50 in further view of McDorman have been fully considered and are not persuasive.
Applicant argues, see pages 11-14, that the term “therapeutically effective amount” as used in claim 30, 41, and 52 is specific to an acute hypotensive state, that the highest therapeutically effective amount (0.128 mg/ml) is not stable in the claimed formulation and is therefore administering formulations with 0.128 mg/ml norepinephrine is not within the scope of the claimed invention, and that the claimed methods include administering norepinephrine formulations at concentrations of 0.016 mg/ml, 0.032 mg/ml, and 0.064 mg/ml. Applicant further argues that Mitidieri only discloses norepinephrine formulations with a concentration between 0.04 mg/ml and 0.2 mg/ml with sodium chloride without differentiating the stability behavior of formulations at specific concentrations within this range, and does not teach or suggest formulations with 0.016 mg/ml or 0.032 mg/ml. However, even if the claimed limitation of a ready-to-use, stable norepinephrine formulation comprising/consisting essentially of/consisting of a therapeutically effective amount of norepinephrine is limited to formulations with a norepinephrine concentration of 0.016 mg/ml, 0.032 mg/ml, or 0.064 mg/ml, the 0.064 mg/ml concentration lies within the 0.04 mg/ml to 0.20 mg/ml concentration range of the antioxidant free norepinephrine formulation disclosed by Mitidieri. Although Mitidieri discloses stable formulations with a concentration between 0.04 mg/ml to 0.20 mg/ml which use sodium chloride as an excipient, Rakesh and Rowe suggest that 5% dextrose is a conventional excipient for pharmaceutical formulations, especially norepinephrine formulations, which would provide one of ordinary skill in the art an expectation of success at using dextrose instead of sodium chloride, which renders the claimed norepinephrine formulation obvious. Furthermore, by incorporating such a formulation into the packaging system of Devouassoux, which may substantially eliminate the dissolved oxygen and therefore eliminate or reduce one route of oxidative degradation, one of ordinary skill in the art would expect the stability of a ready to use, stable norepinephrine formulation comprising a therapeutically effective amount of norepinephrine to be further enhanced.
Applicant further argues, see pages 13-14, that the demonstrated unexpected results of the instability of 0.128 mg/ml norepinephrine in 5% dextrose would not lead one of ordinary skill in the art to expect that a therapeutically effective amount of 0.064 mg/ml in 5% dextrose would be stable. However, as discussed above, Rakesh and Rowe suggest that 5% dextrose is a conventional excipient for pharmaceutical formulations, especially norepinephrine formulations, which would provide one of ordinary skill in the art an expectation of success at using dextrose instead of sodium chloride, with concentrations in the range disclosed by Mitidieri including 0.064 mg/ml, which renders the claimed norepinephrine formulation obvious. Furthermore, by incorporating such a formulation into the packaging system of Devouassoux, which may substantially eliminate the dissolved oxygen and therefore eliminate or reduce one route of oxidative degradation, one of ordinary skill in the art would expect the stability of a ready to use, stable norepinephrine formulation comprising a therapeutically effective amount of norepinephrine to be further enhanced.
Applicant further argues, see page 14, that the process described in Mitidieri for making a stable antioxidant free norepinephrine formulation is specific to vials or ampoules, not the claimed IV bag. However, the process described by Mitidieri involves using inert gas to remove as much dissolved oxygen as possible (Mitidieri: ¶0038-0043), and Devouassoux also teaches the use of inert gas to remove as much dissolved oxygen as possible in packaging systems including IV bags (Devouassoux: ¶0040 and 0067).
Applicant further argues, see pages 14-15, that Rakesh and Rowe do not specifically teach the use of 5% dextrose as an excipient in antioxidant free norepinephrine formulations. However, Mitidieri teaches antioxidant free, low concentration norepinephrine formulations as an improvement over norepinephrine formulations with antioxidants, and Rakesh teaches norepinephrine formulations which use dextrose instead of sodium chloride, and therefore the combination of Mitidieri and Rakesh would provide an expectation of success of an antioxidant free, low concentration norepinephrine formulation with dextrose. Furthermore, even if Rowe is a general pharmaceutical excipient reference that provides no teaching regarding the stability of antioxidant-free norepinephrine formulations in dextrose, Rowe still teaches an advantage of using 5% dextrose, that is preventing local vein irritation following intravenous administration, that would motivate one of ordinary skill in the art to consider using it in the formulation.
Applicant further argues, see pages 15-16, that the Cope Declaration I refutes the idea that the stability is solely a function of the oxygen scavenger acting independently of the composition of the formulation, which applicant alleges the Office to be arguing in the previous Office Action. However, the Office is not arguing that the oxygen scavenger of Devouassoux is solely responsible for stabilizing the formulation. The action of the oxygen scavenger in the packaging system of Devouassoux is to remove dissolved oxygen from the formulation in the primary package, which eliminates or reduces oxidative degradation of the pharmaceutical in the formulation on an ongoing basis. The combination of the preparation methods of Mitidieri, which on their own produce formulations which retain 90% of an initial activity of R-norepinephrine after storage for 120 days as claimed, and the packaging system including an oxygen scavenger of Devouassoux, would lead one of ordinary skill in the art to predict enhanced stability over either Mitidieri or Devouassoux on their own.
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, 41, 43-44, 48, 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 an acute hypotensive state in a subject in need thereof (¶0006-0007 and 0034-0036: “a method of treatment for restoring and/or keeping physiological pressure levels” includes treating hypotension and acute hypotension), the method comprising: administering to a human subject 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 an acute hypotensive state (¶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 a therapeutically effective amount of norepinephrine which is an amount sufficient to treat the acute hypotensive state in a human subject when administered by intravenous infusion (¶0006-0007, 0034-0036, and 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 a therapeutically effective amount of norepinephrine which is an amount sufficient to treat the acute hypotensive state in a human subject when administered by intravenous infusion (¶0006-0007, 0034-0036, and 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 a therapeutically effective amount of norepinephrine which is an amount sufficient to treat the acute hypotensive state in a human subject when administered by intravenous infusion (¶0006-0007, 0034-0036, and 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).
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.
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. 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 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 in view of Rakesh, in further view of Rowe, in further view of Devouassoux, in further view of Inoue, 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 in view of Rakesh, in further view of Rowe, in further view of Devouassoux, in further view of Inoue, 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 in view of Rakesh, in further view of Rowe, in further view of Devouassoux, in further view of Inoue, 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
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARJUNA P CHATRATHI whose telephone number is (571)272-8063. The examiner can normally be reached M-F 8:30-5:00.
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/ARJUNA P CHATRATHI/Examiner, Art Unit 3781
/SARAH AL HASHIMI/Supervisory Patent Examiner, Art Unit 3781
