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 Arguments
Applicant's arguments filed 11/25/2025 have been fully considered but they are not persuasive.
Regarding the rejection of claim 3, Applicant argues that the Office oversimplifies the problem to be solved as merely one of physics. Applicant argues that the problem also requires considering the qualities of the biologic drug being delivered by the syringe, and particularly the possibility of unexpected behavior of the drug. Applicant points to a previously cited reference to Krayukhina which discusses such unexpected behaviors. The examiner does not find this argument convincing. First, Krayukhina found that the viscosity of omalizumab at a concentration of 125 mg/ml (similar to the claimed 150 mg/ml) showed a shear-independent region up to 3000 s-1, followed by a rapid decrease with increasing shear rates, thereby showing shear thinning behavior (page 520). Therefore, the omalizumab composition of the claimed invention would flow as described by Poiseuille’s Law in the shear-independent region, and flow more easily as the shear thinning occurs. This further supports the idea that a smaller diameter needle would result in a shorter fluid delivery time, and lengthening the needle would not provide the expected delivery time lengthening. Therefore, Applicant’s argument is not convincing. Second, the cited references teach exactly the biologic drug that is claimed in the instant invention. Therefore, arguments to the drug behaving in an unexpected way are not convincing as the prior art drug is an identical drug to the claimed drug and therefore would behave in an identical way. Additionally, as noted in the prior Office action, Applicant has not provided any criticality to the needle diameter as the method is described for use with a needle of gauge 25 to gauge 29 (page 7, line 10).
Applicant further argues that Somerville discloses a 26G needle which is larger than the 27G needle, and therefore one of ordinary skill in the art would not look to Poiseuille’s law to reduce the needle size. This argument is not convincing. Cabiri is relied upon to teach the use of a 27G ultra thin wall needle. Ultra thin wall needles have larger inner diameters than the regular or thin wall version of that particular needle gauge, as gauge refers to the outer diameter of the needle. The inner diameter of a regular 26G needle is similar to the inner diameter of an ultra thin wall 27G needle. And as previously noted, there is no criticality to this particular dimension.
Applicant further argues that the 27G needles of Rini are 8mm long and one of ordinary skill in the art would not have been motivated to use a 12.7 mm needle, and doing so would have increased expulsion time. This argument is not convincing. The cited prior art teaches a syringe configured as claimed, including the claimed omalizumab formulation, and the claimed needle size, and therefore is configured to perform in the same manner as the claimed syringe. The disclosure does not provide any additional parameters to the syringe that would affect the performance, so one must assume that a prior art syringe configured as claimed would perform the claimed delivery profile. Additionally, the prior art recognizes that injection duration is a result effective variable controlled by cannula diameter, length and drive force. Furthermore, as noted above, Krayukhina found that omalizumab shows shear thinning at higher shear forces, which explains why some of the parameters will be contrary to those defined by Poiseuille’s law, specifically, the needle having a longer length would perform as claimed.
In conclusion, the prior art teaches a syringe having the claimed drug formulation and needle dimensions, and therefore it must perform as recited in the claim. If Applicant argues that such a syringe would not perform as claimed, then Applicant’s claimed syringe must also not perform as claimed as there is no other elucidated parameter that would explain such a difference in performance between the claimed invention and the prior art syringe.
Applicant argues that Cabiri does not disclose the recited diameter, and that one of ordinary skill in the art would not readily understand the ultra thin walled needle would have an inner diameter of 0.277 mm. this is a mischaracterization of the rejection. The rejection is based on a lack of criticality to the claim 0.277 mm inner diameter. The examiner does not argue that an ultra thin walled needle as taught by Cabiri would necessarily have an inner diameter or 0.277 mm specifically, only that the inner diameter would be larger than the standard 0.24 mm inner diameter of a thin walled 27G needle, meaning that it would be similar in size to the claimed invention. That, in combination with the lack of criticality provided for the claimed dimension results in the obviousness of the claim.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Applicant has not provided any criticality to the claimed parameters which were taught by “cobbling together” prior art. Parameter is a result effective variable as noted in the rejection. The claimed invention does not provide any unexpected results as the delivery of the drug is defined by Poiseuille’s law and divergence from that is understood to be the result of defined shear thinning as discussed by Krayukhina.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 3, 6-10, 12, 45, 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Somerville et al “Immunogenicity and safety of omalizumab in prefilled syringes in patients with allergic (IgE-mediate) asthma (Current Medical Research & Opinion Vol. 30, No. 1, 2014, 59-66) in view of Dubey (EP 3 808 777 A1) in view of Boyden et al (US 9,550,029) in view of Rini et al “Enabling faster subcutaneous delivery of larger volume, high viscosity fluids” (Expert Opinion of Drug Delivery, 19:9, 1165-1176, DOI: 10.1080/17425247.2022.2116425) in view of Cabiri et al (US 9,987,432). [Newly cited references are in bold].
Regarding claim 3, Somerville discloses a method of treating a patient with allergic asthma that is inadequately controlled with inhaled corticosteroids (introduction), comprising administering 1 mL of 150mg/mL omalizumab formulation to the patient subcutaneously by a syringe (page 60, 2nd paragraph), the syringe comprising a reservoir filled with 1 mL of 150 mg/mL omalizumab formulation (page 60, last paragraph). Somerville discloses that the injection is performed subcutaneously by a syringe having a reservoir filled with the above volume of the formulation (introduction). Syringes are known to have a stopper to effectuate expulsion of the formulation from the reservoir.
Claim 3 further calls for the formulation to have 6000 or fewer particles of diameter ≥ 10µm and/or 600 or fewer particles of diameter ≥ 25 µm. Somerville fails to teach this feature. Dubey teaches a stable liquid antibody formulation including omalizumab 150mg/mL (page 2, para. 0005) and further teaches that the formulation contains particles within the claimed range (page 6, subvisible particle). Dubey teaches that this range is beneficial because it mitigates the risk associated with the presence of extraneous particles in injectable solutions (page 5, para. 0039). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the formulation disclosed by Somerville to include 6000 or fewer particles of diameter ≥ 10µm and/or 600 or fewer particles of diameter ≥ 25 µm as taught by Dubey to mitigate the risks associated with the presence of extraneous particles in the injectable solution.
Claim 3 further calls for the needle to have a length of 12.7 mm. Boyden teaches a syringe for subcutaneous injection of a viscous material such as omalizumab (col. 34, lines 39-44) wherein the needle has a length of ½ inch (12.7 mm) which is an appropriate length for a subcutaneous injection (col. 45, lines 46-49). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the needle of Somerville to have a length of 12.7mm as taught by Boyden as this is an appropriate length needle for subcutaneous injection of a viscous biologic such as omalizumab.
Claim 3 further calls for the needle to have a gauge of 27 and 5 bevels on its distal surface. Rini teaches injection of high viscosity fluids (defined as 2.3-30 cP: page 1166, 2nd paragraph). The formulation of the claimed invention is within this range as described by Applicant (spec page 12, lines 1-4; note 1mPa-s = 1cP). Rini teaches that such fluids can be injected using a needle having 27G, which facilitates ease of use and effectiveness of the injection (page 1166, 1st paragraph, last paragraph), and further shows that the needle has 5 bevels which improves ease of insertion thereby reducing pain (see fig. 1b annotated below). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the syringe taught by Somerville to have a 27G diameter and 5 bevels as taught by Rini because such a needle is appropriate for delivery of a viscous solution without excess difficulty for the user thereby allowing self injection.
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Claim 3 calls for the needle to be 27G and have a minimum internal diameter of 0.277mm. The examiner notes that Applicant has not provided criticality to this inner diameter, as different inner diameters are listed in the disclosure as suitable for use in this method, including 27G needles having different inner diameters. Cabiri teaches a syringe for injection of a viscous fluid, wherein the needle is 27G ultra thin wall needle (col. 6, lines 56-58). Cabiri does not explicitly disclose the inner diameter of the needle, however an ultra thin wall needle has a larger inner diameter than the regular or thin wall version of that gauge needle, and therefore the needle has an inner diameter larger than 0.240mm (27G thin wall inner diameter). Additionally, as discussed above with regard to Poiseuille’s law, the relationship between inner diameter of the needle and flow rate is known and therefore there would be no unexpected results stemming from a change in the inner diameter of the needle. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the 27G needle taught above to be the ultra thin wall needle as taught by Cabiri thereby increasing the inner diameter to achieve a greater flow rate of the fluid through the needle and reduce injection time which reduces patient discomfort. Additionally, there is no criticality to the specific inner diameter and therefore, it would have been obvious to modify the ultra thin wall needle to have the inner diameter as claimed as doing so would not provide unexpected results.
Claim 3 further calls for when a constant 10N force is applied to the stopper, the syringe is configured to expel 1mL of the formulation in less than 5 seconds, or the syringe is configured to expel 0.5mL of the formulation is less than 4 seconds. Rini does not specifically disclose this limitation, however, achieving this configuration would have been routine optimization of a result effective variable. Rini teaches that reducing injection duration for high viscosity formulations can be accomplished by modifying system components that regulate delivery rate, such as cannula diameter, cannula length, and drive forces (page 1166, 2nd paragraph). This relationship is defined by Poiseuille’s law as discussed above. Rini further teaches that in experiments performed, 2mL of a solution having a viscosity similar to the claimed invention (15.3 cP at room temp), using a 27G needle and a 23N force would be delivered within approximately 13 seconds (page 1169, table b). This is twice the volume of the 1 mL delivery, and 4 times the 0.5 delivery in the claimed invention, and therefore, it is understood that delivery of these smaller volumes would take proportionately less time. Additionally, as discussed above, the needle has been modified to have a larger inner diameter which would further reduce the injection time. It would have been a matter of routine optimization of a result effective variable to arrive at the claimed invention because Rini recognizes that reducing injection duration is beneficial in increasing ease of use of the device, and is controlled by modifying cannula diameter, length and drive force. Additionally, Applicant has not provided criticality for the specific injection durations.
Claim 6 calls for the syringe to be configured to expel 1 mL of the formulation within a 5 seconds when a 10N force is applied to the stopper, or within 3 second when a force of 17N is applies, or within 2 second when a force of 30N is applied. As discussed above, this is interpreted to be routine optimization of a result effective variable and it would have been obvious to arrive at the claimed invention because Rini recognizes that reducing injection duration is beneficial in increasing ease of use of the device, and is controlled by modifying cannula diameter, length and drive force. Additionally, Applicant has not provided criticality for the specific injection durations.
Claim 7 calls for the syringe to be configured to expel X mL of formulation in less than 5 seconds to about 4 second when a 10N force is applied to the stopper, or less than 3.5 seconds to about 2 seconds when a 17N force is applied, or less than 2 seconds to about 1 second when a constant force of 30N is applied. As discussed above, this is interpreted to be routine optimization of a result effective variable and it would have been obvious to arrive at the claimed invention because Rini recognizes that reducing injection duration is beneficial in increasing ease of use of the device, and is controlled by modifying cannula diameter, length and drive force. Additionally, Applicant has not provided criticality for the specific injection durations.
Claim 8 calls for the syringe to be configured to expel 0.5 mL of formulation in less than 2 second when a 17N force is applied to the stopper, or less than 1 second when a 30N force is applied. As discussed above, this is interpreted to be routine optimization of a result effective variable and it would have been obvious to arrive at the claimed invention because Rini recognizes that reducing injection duration is beneficial in increasing ease of use of the device, and is controlled by modifying cannula diameter, length and drive force. Additionally, Applicant has not provided criticality for the specific injection durations.
Claim 9 calls for the syringe to be configured to expel X mL of formulation in less than 4 seconds to about 2 second when a 10N force is applied to the stopper, or less than 2 seconds to about 1 second when a 17N force is applied, or less than 1 second when a constant force of 30N is applied. As discussed above, this is interpreted to be routine optimization of a result effective variable and it would have been obvious to arrive at the claimed invention because Rini recognizes that reducing injection duration is beneficial in increasing ease of use of the device, and is controlled by modifying cannula diameter, length and drive force. Additionally, Applicant has not provided criticality for the specific injection durations.
Claim 10 calls for the syringe to contain at least 76% main omalizumab charge variant measured by ion exchange chromatography after being filled with 150 mg/mL omalizumab solution stored at 5⁰C ± 1⁰C, or at least 77% main omalizumab charge variant measured by ion exchange chromatography after being filled with 150 mg/mL omalizumab solution stored at 5 ⁰C ± 1⁰C for 2.5 months. Applicant has not provided any criticality to this parameter. Charge variant is related to the purity or stability of the formulation. Purity and stability can be affected by various factors including the product formulation, the materials in the container, exposure to heat and light, etc. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the prior art discussed above to arrive at the claimed invention because maintaining purity of the formulation during storage prior to use is a common priority in the art and can be achieved in a variety of ways including refrigeration and shielding from UV exposure as evidenced by Scholz et al (US 2019/0216925) page 7, para. 0075.
Claim 12 calls for the proportion of the first peak of the syringe measured by hydrophobic interaction chromatography is at least 68% after filling with 150 mg/mL omalizumab solution stored at 5⁰C ± 1⁰C, or at least 62% after being filled with 150 mg/mL omalizumab solution stored at 5 ⁰C ± 1⁰C for 2.5 months. Applicant has not provided any criticality to these parameters. This measurement is an alternative measure of purity and stability to the ion exchange chromatography discussed with regard to claim 10 above. Therefore, it would have been obvious to one of ordinary skill in the invention to modify the prior art discussed above to arrive at the claimed invention for similar reasons discussed above, specifically because maintaining purity of the formulation during storage prior to use is a common priority in the art and can be achieved in a variety of ways including refrigeration and shielding from UV exposure.
Regarding claim 45, Somerville discloses a syringe comprising a reservoir filled with 1 mL of 150mg/mL omalizumab formulation (page 60, 2nd paragraph, last paragraph). Somerville discloses that the injection is performed by a syringe, and syringes necessarily a stopper and a needle in order to perform the injection.
Claim 45 further calls for the formulation to have 6000 or fewer particles of diameter ≥ 10µm and/or 600 or fewer particles of diameter ≥ 25 µm. Somerville fails to teach this feature. Dubey teaches a stable liquid antibody formulation including omalizumab 150mg/mL (page 2, para. 0005) and further teaches that the formulation contains particles within the claimed range (page 6, subvisible particle). Dubey teaches that this range is beneficial because it mitigates the risk associated with the presence of extraneous particles in injectable solutions (page 5, para. 0039). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the formulation disclosed by Somerville to include 6000 or fewer particles of diameter ≥ 10µm and/or 600 or fewer particles of diameter ≥ 25 µm as taught by Dubey to mitigate the risks associated with the presence of extraneous particles in the injectable solution.
Claim 45 further calls for the needle to have a length of 12.7 mm. Boyden teaches a syringe for subcutaneous injection of a viscous material such as omalizumab (col. 34, lines 39-44) wherein the needle has a length of ½ inch (12.7 mm) which is an appropriate length for a subcutaneous injection (col. 45, lines 46-49). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the needle of Somerville to have a length of 12.7mm as taught by Boyden as this is an appropriate length needle for subcutaneous injection of a viscous biologic such as omalizumab.
Claim 45 further calls for the needle to have a gauge of 27 and 5 bevels on its distal surface. Rini teaches injection of high viscosity fluids (defined as 2.3-30 cP: page 1166, 2nd paragraph). The formulation of the claimed invention is within this range as described by Applicant (spec page 12, lines 1-4; note 1mPa-s = 1cP). Rini teaches that such fluids can be injected using a needle having 27G, which facilitates ease of use and effectiveness of the injection (page 1166, 1st paragraph, last paragraph), and further shows that the needle has 5 bevels which improves ease of insertion thereby reducing pain (see fig. 1b annotated above). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the syringe taught by Somerville to have a 27G diameter and 5 bevels as taught by Rini because such a needle is appropriate for delivery of a viscous solution without excess difficulty for the user thereby allowing self injection.
Claim 45 calls for the needle to be 27G and have a minimum internal diameter of 0.277mm. The examiner notes that Applicant has not provided criticality to this inner diameter, as different inner diameters are listed in the disclosure as suitable for use in this method, including 27G needles having different inner diameters. Cabiri teaches a syringe for injection of a viscous fluid, wherein the needle is 27G ultra thin wall needle (col. 6, lines 56-58). Cabiri does not explicitly disclose the inner diameter of the needle, however an ultra thin wall needle has a larger inner diameter than the regular or thin wall version of that gauge needle, and therefore the needle has an inner diameter larger than 0.240mm (27G thin wall inner diameter). Additionally, as discussed above with regard to Poiseuille’s law, the relationship between inner diameter of the needle and flow rate is known and therefore there would be no unexpected results stemming from a change in the inner diameter of the needle. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the 27G needle taught above to be the ultra thin wall needle as taught by Cabiri thereby increasing the inner diameter to achieve a greater flow rate of the fluid through the needle and reduce injection time which reduces patient discomfort. Additionally, there is no criticality to the specific inner diameter and therefore, it would have been obvious to modify the ultra thin wall needle to have the inner diameter as claimed as doing so would not provide unexpected results.
Claim 45 further calls for when a constant 10N force is applied to the stopper, the syringe is configured to expel 1mL of the formulation in less than 5 seconds, or the syringe is configured to expel 0.5mL of the formulation is less than 4 seconds. Rini does not specifically disclose this limitation, however, achieving this configuration would have been routine optimization of a result effective variable. Rini teaches that reducing injection duration for high viscosity formulations can be accomplished by modifying system components that regulate delivery rate, such as cannula diameter, cannula length, and drive forces (page 1166, 2nd paragraph). This relationship is defined by Poiseuille’s law as discussed above. Rini further teaches that in experiments performed, 2mL of a solution having a viscosity similar to the claimed invention (15.3 cP at room temp), using a 27G needle and a 23N force would be delivered within approximately 13 seconds (page 1169, table b). This is twice the volume of the 1 mL delivery, and 4 times the 0.5 delivery in the claimed invention, and therefore, it is understood that delivery of these smaller volumes would take proportionately less time. Additionally, as discussed above, the needle has been modified to have a larger inner diameter which would further reduce the injection time. It would have been a matter of routine optimization of a result effective variable to arrive at the claimed invention because Rini recognizes that reducing injection duration is beneficial in increasing ease of use of the device, and is controlled by modifying cannula diameter, length and drive force. Additionally, Applicant has not provided criticality for the specific injection durations.
Claim 46 calls for the syringe to be configured to expel 1 mL of the formulation within less than 5 seconds to 4 about 4 seconds when a 10N force is applied to the stopper. As discussed above, this is interpreted to be routine optimization of a result effective variable and it would have been obvious to arrive at the claimed invention because Rini recognizes that reducing injection duration is beneficial in increasing ease of use of the device, and is controlled by modifying cannula diameter, length and drive force. Additionally, Applicant has not provided criticality for the specific injection durations.
Claim(s) 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Somerville in view of Rini in view of Dubey as applied to claim 18 above, and further in view of Adams et al (US 10,751,417).
Regarding claim 28, Rini further teaches that the needle has 3 surface bevels on its distal surface (page 1167, fig. b). it would have been obvious to one of ordinary skill in the art before the effective filing date to use a needle having 3 distal bevels as taught by Rini to perform the injection of Somerville to provide sharp surface to puncture the tissue thereby reducing pain of insertion and increasing patient compliance.
Claim(s) 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Somerville in view of Dubey in view of Boyden in view of Rini in view of Cabiri as applied to claim 3 above, and further in view of Novak et al (US 10,160,799).
Claim 24 calls for the stopper to have a fluoro-resin product contacting side. Somerville teaches that the omalizumab is contained in a pre-filled syringe as discussed above but fails to disclose the material of the stopper. Novak teaches container for holding omalizumab (col. 103, line 44) wherein the container is sealed by fluoro-resin laminated stopper (col. 110, line 1) which does not react with the drug in the container. While Novak teaches a stopper for a vial, this is analogous to the syringe stopper taught by Somerville since the syringe is pre-filled and intended for long term storage of the drug in the same way that a vial with a pierceable stopper is intended for long term storage of the drug. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the stopper of Somerville to include a fluoro-resin on the product contacting side as taught by Novak to provide an inert surface to prevent degradation of the drug during storage.
Claim(s) 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Somerville in view of Dubey in view of Boyden in view of Rini in view of Cabiri as applied to claim 3 above, and further in view of Hetting (CN 105324143 B). For ease of discussion, see machine translation attached herewith.
Claim 25 calls for the stopper to have a B2-40 UV cured lubrication coating or is lubricated with 1000cSt silicone oil. Hetting teaches a syringe having a stopper that is lubricated with 1000cSt silicone oil to reduce friction and thereby increase ease of injection (page 4, 2nd paragraph). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the stopper of Somerville to be lubricated with 1000cSt silicone oil as taught by Hetting to decrease friction of the stopper and increase ease of use of the syringe.
Claim(s) 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Somerville in view of Dubey in view of Boyden in view of Rini in view of Cabiri as applied to claim 3 above, and further in view of Ito et al (US 7,648,487).
Claim 27 differs from the teachings above in calling for the syringe barrel to have a coating of 0.4±0.2mg of polydimethylsiloxane. Ito teaches a syringe barrel having a coating of polydimethylsiloxane to improve sliding of the stopper through the syringe barrel thereby increase ease of use (col. 3, lines 38-39). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the syringe barrel of Somerville to include a polydimethylsiloxane coating as taught by Ito to provide a lubricious surface to allow the stopper to slide more easily and therefore increase ease of use. Ito discloses 10 mg of polydimentylsiloxane in a 20 mL syringe (col. 8, lines 51-53). The syringe of the instant invention is a 1mL syringe and therefore an amount of polydimethylsiloxane is smaller by a factor of 20 is required to provide the lubricious coating. Applicant has not provided criticality to this specific amount of polydimethylsiloxane. Therefore, it would have been obvious to one of ordinary skill in the art at the time of invention that the syringe of Somerville would require 0.4 ±0.2mg of polydimethylsiloxane for the coating of a 1mL syringe based on the teachings of Ito, or alternatively, it would have been a matter of routine experimentation to arrive at the appropriate amount of polymethylsiloxane for the syringe as there is no criticality to this particular value.
Claim(s) 29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Somerville in view of Dubey in view of Boyden in view of Rini in view of Cabiri as applied to claim 3 above, and further in view of Soane et al (US 2021/0113697).
Claim 29 calls for the apparent viscosity of the 150mg/mL formulation to be 12-14 mPa-S, or when measured at a shear rate of 200s-1 is: 24.7 ± 0.5 mPa-s at 5.0 ± 0.2⁰C, 15.3 ± 0.5 mPa-s at 15.0 ± 0.2⁰C, 11.4 ± 0.5 mPa-s at 25.0 ± 0.2⁰C, or 7.2 ± 0.5 mPa-s at 40.0 ± 0.2⁰C. Soane teaches that the viscosity of omalizumab can be adjusted based on the excipient solution used and a viscosity of 7 or 21 cP can be achieved (table 51). Applicant has not provided criticality to the claimed viscosity ranges. Additionally, Rini recognizes that the viscosity of the formulation affects the ability of the dose to be delivered quickly through a needle, and particularly through a needle that is thin enough to be inserted with minimal pain (page 1166, 2nd paragraph). Therefore, it would have been a matter of routine optimization of a result effective variable to modify the excipients in the omalizumab formulation to be within the claimed range to achieve good flow characteristics through the injection needle.
Claim(s) 30, 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Somerville in view of Dubey in view of Boyden in view of Rini in view of Cabiri as applied to claim 3 above, and further in view of Richard et al (US 4,252,118).
Claim 30 calls for the syringe to have a latex-fee needle shield. Richard teaches a prefilled syringe that includes a needle shield (fig. 6) to ensure that the needle remains sterile prior to use. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the syringe of Somerville to include a shield as taught by Richard to ensure that the needle remains sterile prior to use. Richard does not disclose that the shield is latex-free, however it is well known in the medical arts to avoid the use of latex, particularly in materials that will be handled by a patient such as the cap on a prefilled syringe for self-injection because latex allergies are very common. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make the cap latex-free as it is well known in the art to avoid latex because many people have latex allergies.
Regarding claim 31, Richard further teaches that the syringe has a round flange at a proximal end of the reservoir (fig. 6) to provide a support surface for the user’s fingers while they depress the plunger with their thumb to allow for easy one handed use of the syringe. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the syringe of Somerville to include a flange at the proximal end of the reservoir as taught by Richard to allow easy one handed use of the syringe.
Claim(s) 32- 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Somerville in view of Dubey in view of Boyden in view of Rini in view of Cabiri as applied to claim 3 above, and further in view of Moser et al (US 2020/0246555).
Claim 32 calls for the syringe to have a length of 54.0 ± 0.5mm and an internal diameter of 6.35 mm ± 0.05mm. Applicant has not provided a criticality to these parameters. Moser teaches a syringe for injection of a viscous fluid (abstract), and further discloses that the length and internal diameter of the syringe can be adjusted to achieve the desired effects (page 4, para. 0050). Moser teaches syringes having various lengths and internal diameters for injection of a volume of roughly 1 to 3 mL, the lengths in the range of 56 mm and diameters in the range of 6.45 mm (page 4, para. 0045-0047). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the syringe of Somerville to have the claimed dimensions because there is no criticality to those specific dimensions and Moser teaches that these dimensions similar to those known in the art for delivering a similar volume of a viscous fluid. Therefore, the claimed invention is not patentably distinct from the prior art.
Claim 33 calls for the stopper to have a maximum external diameter of 6.67 mm to 7.10 mm and/or a length of 7.85 ± 0.4 mm, or a maximum external diameter of 6.70 ± 0.15 mm and/or a length of 7.85 ± 0.4 mm. Applicant has not provided criticality to these parameters. Moser further discloses that the stopper has a length of 6.9 mm (page 7, para. 0080). Since there is no criticality to the claimed length of the stopper and Applicant has not described any particular benefit to the length of the stopper, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention given the disclose of a similarly sized stopper by Moser.
Claim 34 calls for the stopper to have at least one circumferential rib of outer diameter 6.60 ± 0.15 mm. Moser teaches the stopper having at least one circumferential rib (fig. 4) and wherein the internal diameter of the syringe is 6.45 mm (page 4, para. 0045). Since the stopper outer diameter is close fit with the inner diameter of the syringe barrel to form a leak-proof sliding engagement, the outer diameter of the stopper is within the claimed range. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to for the stopper of Somerville with a rib as taught by Moser to allow the desired sealing force while allowing the stopper to slide within the barrel, and further to provide a syringe and stopper having corresponding diameters within the claimed range as taught by Moser because Applicant has not provided criticality to these dimensions and they are known to be suitable dimensions for a syringe that delivers 1 mL of viscous fluid.
Claim(s) 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Somerville in view of Dubey in view of Boyden in view of Rini in view of Cabiri as applied to claim 3 above, and further in view of Sigg et al (US 9,220,631).
Regarding claim 39, Sigg et all teaches a filled syringe having a break loose force measuring at 190mm/min between 2 and 5 N to allow for ease of use of the syringe and steady injection of the fluid therefrom (col. 5, lines 42-45). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the syringe of Somerville to have a break looks force of about 2 N as taught by Sigg to allow the user to easily move the plunger to inject the fluid to ensure smooth injection and reduce pain.
Claim(s) 41 is/are rejected under 35 U.S.C. 103 as being unpatentable over Somerville in view of Dubey in view of Boyden in view of Rini in view of Cabiri as applied to claim 3 above, and further in view of Doyle (US 6,613,022).
Claim 41 calls for a needle shield device comprising a needle sleeve and a plunger, wherein the force applied to the plunger to expel the formulation unlatches the needle sleeve so the sleeve can cover the needle after use. Doyle teaches a syringe received in a needle shield device including a needle sleeve and a plunger such that upon completion of the injection with the plunger, the needle sleeve is unlatched and automatically covers the needle after the injection (col. 19, lines 15-25; fig. 19). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the syringe of Somerville to include the needle shield device as taught by Doyle to provide an automatic shielding of the needle upon completion of the injection to prevent accidental sticks with a used needle.
Claim(s) 14, 48, 57 is/are rejected under 35 U.S.C. 103 as being unpatentable over Somerville in view of Dubey in view of Boyden in view of Rini in view of Cabiri as applied to claims 3 or 45 above, and further in view of Xolair Label.
Claim 14 calls for the syringe to contain at least 0.4mg/mL polysorbate 20. The Xolair Label teaches that the 150mg/ml omalizumab formulation contains 0.4 mg/mL polysorbate 20 (page 26, Xolair for Injection). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the omalizumab used by Somerville would have the formulation described above because this is the standard formulation for Xolair provided from the manufacturer.
Claims 48 and 57 calls for the 105mg/ml omalizumab formulation to be 150mg/ml antibody with 42.1 mg/ml L-arginine hydrochloride, 1.37 mg/ml L-histidine, 2.34 mg.ml L-histidine hydrochloride monohydrate, 0.4 mg/mL polysorbate 20 as an aqueous solution. The Xolair label teaches that this is the formulation for the 150mg/ml concentration of omalizumab (page 26, Xolair for Injection). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the omalizumab used by Somerville would have the formulation described above because this is the standard formulation for Xolair provided from the manufacturer.
Conclusion
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LAURA A. BOUCHELLE
Primary Examiner
Art Unit 3783
/LAURA A BOUCHELLE/Primary Examiner, Art Unit 3783