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 .
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description:
51 as shown in Fig. 4.
Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 2, 3, and 7 are objected to because of the following informalities:
Claim 2 recites “the composition.” The Examiner suggests amending this to recite “the liquid pharmaceutical composition” to increase the claim language consistency when reciting this structure within the claim.
Claim 3 recites “wherein the headspace has a cylindrical volume domain portion which volume domain portion has…a specific height, which specific height is measured.” The Examiner suggests amending this to recite “wherein the headspace has a cylindrical volume domain portion [[which]] wherein the volume domain portion has…a specific height, [[which]] wherein the specific height is measured” in order to properly claim dependency for these structures.
Claim 7 recites “the composition.” The Examiner suggests amending this to recite “the liquid pharmaceutical composition” to increase the claim language consistency when reciting this structure within the claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1 and 18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wei (US 2018/0250474 A1).
Wei is cited in the IDS filed 7 January 2026.
With regards to claim 1, Wei discloses (see Figs. 1 – 6) a system (10) (see [0020]) for storing a pharmaceutical composition (106) (see [0020]) at low temperatures (see [0005], [0009], [0010]), the system comprising:
a pharmaceutical container (see Fig. 1) having a barrel (103) (see [0020]), a stopper (105) (see [0020]) which fluidly closes a first end of the barrel (see at 103b in Fig. 2), and a closure (104) (see [0020]) which fluidly closes a second end of the barrel (see at 103a in Fig. 2); and
a liquid pharmaceutical composition (106) (see [0020]) and a gas (107) (see [0020]) both arranged within the barrel of the container between the stopper and the closure (see Fig. 3).
With regards to claim 18, Wei discloses the claimed invention of claim 1, and Wei further discloses wherein a position of the stopper (105) moves 4.0 mm or less along a rotation axis of the barrel when the system is cooled from 20°C to -20°C (see [0005], [0009], and [0010] which describe syringe piston movement being avoided during the freezing process wherein when the syringe piston movement is avoided the movement is 0 mm which is 4.00 mm or less).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 2 – 4, 7, and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wei in view of Pedrussio et al. (US 2018/0264111 A1; hereinafter referred to as “Pedrussio”).
With regards to claim 2, Wei discloses the claimed invention of claim 1, and Wei further discloses (see Figs. 1 – 6) wherein, for a vertical orientation of the container (see Fig. 3 and [0022]) with the first end (see at 103b in Fig. 2) being at the bottom and the second end (see at 103a in Fig. 2) being at the top, a volume enclosed by the barrel (see at 106, 107 in Fig. 3) between the stopper (105) and the closure (104) which is occupied by the gas is defined as a headspace of the system (see at 107 in Fig. 3, [0020], and [0022]).
However Wei is silent with regards to wherein, at room temperature, the volume occupied by the headspace is 1% or more of a volume occupied by the composition.
Nonetheless Pedrussio, which is within the analogous art of pharmaceutical products (see abstract and title), teaches wherein, at room temperature, the volume occupied by the headspace is 1% or more of a volume occupied by the composition (see [0097] “The volume of the headspace within the pre-filled syringe is typically less than 30% of the volume of the lg solution, preferably less than 25%, more preferably less than 20%, even more preferably it is less than 15%, most preferably less than 10%, for example between 5 and 10%%”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the volume occupied by the headspace of the system of Wei in view of a teaching of Pedrussio such that at room temperature, the volume occupied by the headspace is 1% or more of a volume occupied by the composition. One of ordinary skill in the art would have been motivated to make this modification because Pedrussio teaches a variety of headspace volumes that typically are within the pre-filled syringe (see [0097] of Pedrussio). Here, the variety of volume occupied by the headspace assists in the stability and efficacy of pharmaceutical product within the syringe.
The system of Wei modified in view of a teaching of Pedrussio will hereinafter be referred to as the system of Wei and Pedrussio.
With regards to claim 3, the system of Wei and Pedrussio teaches the claimed invention of claim 2, and Wei further teaches (see Figs. 1 – 6) wherein the headspace (see at 107 in Fig. 3) has a cylindrical volume domain portion which volume domain portion has a specific diameter equal to an inside diameter of the barrel (see at 107 in Fig. 3 and the diameter of the air bubble equal to the inside diameter of the barrel 103) and a specific height (see at 107 in Fig. 3 and the specific height shown of the air bubble), which specific height is measured from a central point of the stopper (105) to a surface of the liquid pharmaceutical composition facing the stopper.
However Wei is silent with regards to wherein the specific height has a value of 0.1 mm or more.
Nonetheless Pedrussio, which is within the analogous art of pharmaceutical products (see abstract and title), teaches the specific height has a value of 0.1 mm or more (see [0097] “the headspace in smaller syringes (5 ml or less) is typically around 2 to 3 mm of the syringe barrel, in larger syringes about 3 to 5 mm. However, the head space can be further reduced by using the vacuum stoppering technique.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the specific height of the headspace of the system of Wei and Pedrussio in view of a further teaching of Pedrussio such that the specific height has a value of 0.1 mm or more. One of ordinary skill in the art would have been motivated to make this modification because Pedrussio teaches a variety of specific heights for the headspace that typically are within the pre-filled syringe (see [0097] of Pedrussio). Here, the variety of specific heights of the headspace assists in the stability and efficacy of pharmaceutical product within the syringe.
With regards to claim 4, the system of Wei and Pedrussio teaches the claimed invention of claim 3, however, Wei is silent with regards to wherein the specific height is 0.2 mm or more and/or 15 mm or less.
Nonetheless Pedrussio, which is within the analogous art of pharmaceutical products (see abstract and title), teaches wherein the specific height is 0.2 mm or more and/or 15 mm or less (see [0097] “the headspace in smaller syringes (5 ml or less) is typically around 2 to 3 mm of the syringe barrel, in larger syringes about 3 to 5 mm. However, the head space can be further reduced by using the vacuum stoppering technique.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the specific height of the headspace of the system of Wei and Pedrussio in view of a further teaching of Pedrussio such that the specific height is 0.2 mm or more and/or 15 mm or less. One of ordinary skill in the art would have been motivated to make this modification because Pedrussio teaches a variety of specific heights for the headspace that typically are within the pre-filled syringe (see [0097] of Pedrussio). Here, the variety of specific heights of the headspace assists in the stability and efficacy of pharmaceutical product within the syringe.
With regards to claim 7, the system of Wei and Pedrussio teaches the claimed invention of claim 2, however, Wei is silent with regards to wherein, at room temperature, the headspace is a volume which is 1.3 % or more and/or 20 % or less of the volume occupied by the composition.
Nonetheless Pedrussio, which is within the analogous art of pharmaceutical products (see abstract and title), wherein, at room temperature, the headspace is a volume which is 1.3 % or more and/or 20 % or less of the volume occupied by the composition (see [0097] “The volume of the headspace within the pre-filled syringe is typically less than 30% of the volume of the lg solution, preferably less than 25%, more preferably less than 20%, even more preferably it is less than 15%, most preferably less than 10%, for example between 5 and 10%%.” Wherein the lg solution is the composition).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the volume of the headspace of the system of Wei and Pedrussio in view of a further teaching of Pedrussio such that at room temperature, the headspace is a volume which is 1.3 % or more and/or 20 % or less of the volume occupied by the composition. One of ordinary skill in the art would have been motivated to make this modification because Pedrussio teaches a variety of volumes of headspace that typically are within the pre-filled syringe (see [0097] of Pedrussio). Here, the variety of volume occupied by the headspace assists in the stability and efficacy of pharmaceutical product within the syringe.
With regards to claim 8, the system of Wei and Pedrussio teaches the claimed invention of claim 2, and Wei further discloses wherein the system (10) is designed in such a way that, at room temperature, the barrel (103), the stopper (105) and/or the liquid pharmaceutical composition (106) are adapted to each other in such a way, that in case of an expansion of the liquid pharmaceutical composition during cooling the system to a freezing point of the liquid pharmaceutical composition (see [0005], [0009], and [0010]), at least one of the following conditions apply:
the liquid pharmaceutical composition can expand or expands by displacing and/or compressing the gas, hence, reducing the volume of the headspace (see [0023] “Restriction of the movement of the push rod along the syringe barrel axis can help to maintain sterility during freezing process, terminal sterilization operations, air transportation or other operations in which the air pressure within the variable volume chamber or outside the chamber may change. During such operations any gas trapped within the variable volume chamber, or bubbles that may form in a liquid therein, may change in volume and thereby cause the syringe piston to move.”);
a maximal force applied to the stopper by the liquid pharmaceutical composition and/or the gas is lower than a break loose force of the stopper;
the stopper moves 5 mm or less (see [0009] – [0010] which describes that the syringe piston movement is avoided during the freezing process wherein since the syringe piston movement is avoided then the stopper moves 5 mm or less because the syringe piston movement would be zero); or
the stopper moves 0.01 mm or more.
Claim(s) 5 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wei and Pedrussio as applied to claims 2 and 3 above, and further in view of Silverman et al. (US 2020/0146280 A1; hereinafter referred to as “Silverman”).
With regards to claim 5, the system of Wei and Pedrussio teaches the claimed invention of claim 3, however, Wei is silent with regards to wherein a ratio [mm/mm] of the inside diameter of the barrel and the specific height is 0.3 or more and/or 10 or less.
Nonetheless Pedrussio, which is within the analogous art of pharmaceutical products (see abstract and title), teaches the headspace in smaller syringes (5 ml or less) is typically around 2 to 3 mm of the syringe barrel, in larger syringes about 3 to 5 mm. However, the head space can be further reduced by using the vacuum stoppering technique (see [0097]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the specific height of the headspace of the system of Wei and Pedrussio in view of a further teaching of Pedrussio such that the headspace is around 2 to 5 mm. One of ordinary skill in the art would have been motivated to make this modification because Pedrussio teaches a variety of specific heights for the headspace that typically are within the pre-filled syringe (see [0097] of Pedrussio). Here, the variety of specific heights of the headspace assists in the stability and efficacy of pharmaceutical product within the syringe.
However, neither Wei nor Pedrussio teaches the inner diameter of barrel.
Nonetheless Silverman, which is within the analogous art of syringes (see [0038]), teaches the inner diameter of barrel ranging from 6.0 – 6.4 mm (see [0038] “the barrel lumen has an internal diameter of about 6.0, 6.1, 6.2, 6.3, or 6.4 mm”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the inner diameter of the barrel of the system of Wei and Pedrussio in view of a teaching of Silverman such that the inner diameter of the barrel ranges from 6.0 – 6.4 mm. One of ordinary skill in the art would have been motivated to make this modification because Silverman teaches that the inner diameter of the barrel may be a variety of ranges (see [0038] of Silverman). Here, adjusting the inner diameter of the barrel allows for the adjustment of the amount of pharmaceutical composition that may be stored within the syringe.
The system of Wei and Pedrussio modified in view of a teaching of Silverman will hereinafter be referred to as the system of Wei, Pedrussio, and Silverman.
Here, the system of Wei, Pedrussio, and Silverman teaches a ratio [mm/mm] of the inside diameter of the barrel and the specific height is 0.3 or more and/or 10 or less. Pedrussio teaches the specific height ranges from 2 – 5 mm and Silverman teaches the inner diameter of the barrel ranges from 6.0 – 6.4 mm. Using these ranges multiple combinations exist where the ratio of the inside diameter of the barrel and specific height falls within the claimed range. For example, see when the inner diameter of the barrel equals 6 mm and the specific height equals 5 mm the ratio is 1.2 or when the inner diameter of the barrel equals 6 mm and the specific height equals 3 mm the ratio is 2.
With regards to claim 6, the system of Wei and Pedrussio teaches the claimed invention of claim 2, however, Wei is silent with regards to wherein at least one of the following equations is fulfilled: (X/Y)/Z≤V; or W≤(X/Y)/Z; wherein X is a volume in milliliters of the liquid pharmaceutical composition at room temperature, Y is a volume in milliliters of the headspace at room temperature, Z is an inner diameter in millimeters of the barrel, V in 1/millimeters is 1.5, and W in 1/millimeters is 0.01.
Nonetheless Pedrussio, which is within the analogous art of pharmaceutical products (see abstract and title), teaches the volume of the pharmaceutical composition ranges from 1 mL to 120 mL (see [0096]), the volume of the headspace is 5% - 30% less than the volume of the pharmaceutical composition which equals a volume of the headspace equaling a range of 0.05 mL to 6 mL (at 5%) or a range of 0.3 mL to 36 mL (at 30%) (see [0097]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the volume of the pharmaceutical composition and the headspace of the system of Wei and Pedrussio in view of a further teaching of Pedrussio such that the volume of the pharmaceutical composition is between 1 mL to 120 mL and the volume of the headspace at room temperature between 0.05 mL to 6 mL or 0.3 mL to 36 mL. One of ordinary skill in the art would have been motivated to make this modification because Pedrussio teaches a variety of volumes of the pharmaceutical composition and volume of the headspace (see [0096] and [0097] of Pedrussio). Here, the varying range of volumes of pharmaceutical composition is beneficial in order to provide the proper dosage to the patient and the variety volumes of the headspace assists in the stability and efficacy of pharmaceutical product within the syringe.
However, neither Wei nor Pedrussio teaches the inner diameter of the barrel.
Nonetheless Silverman, which is within the analogous art of syringes (see [0038]), teaches the inner diameter of barrel ranging from 6.0 – 6.4 mm (see [0038] “the barrel lumen has an internal diameter of about 6.0, 6.1, 6.2, 6.3, or 6.4 mm”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the inner diameter of the barrel of the system of Wei and Pedrussio in view of a teaching of Silverman such that the inner diameter of the barrel ranges from 6.0 – 6.4 mm. One of ordinary skill in the art would have been motivated to make this modification because Silverman teaches that the inner diameter of the barrel may be a variety of ranges (see [0038] of Silverman). Here, adjusting the inner diameter of the barrel allows for the adjustment of the amount of pharmaceutical composition that may be stored within the syringe.
The system of Wei and Pedrussio modified in view of a teaching of Silverman will hereinafter be referred to as the system of Wei, Pedrussio, and Silverman.
Here the system of Wei, Pedrussio, and Silverman teaches wherein at least one of the following equations is fulfilled: (X/Y)/Z≤V; or W≤(X/Y)/Z; wherein X is a volume in milliliters of the liquid pharmaceutical composition at room temperature, Y is a volume in milliliters of the headspace at room temperature, Z is an inner diameter in millimeters of the barrel, V in 1/millimeters is 1.5, and W in 1/millimeters is 0.01.
Here, Pedrussio teaches the volume of the liquid pharmaceutical composition ranging from 1 mL to 120 mL and the volume of the headspace at room temperature ranging from 0.05 mL to 6 mL or 0.3 mL to 36 mL. Next Silverman teaches the inner diameter of the barrel of the system ranges from 6.0 – 6.4 mm. There are multiple combinations of these ranges of the volume of the liquid pharmaceutical composition, volume of the headspace, and inner diameter that read upon the equation (X/Y)/Z ≤ V. For example, when X = 120 mL, Y = 36 mL and Z = 6 mm equates to 0.556 1/millimeters which is less than 1.5 1/millimeters when V = 1.5 1/millimeters. Similarly, when X = 120 mL, Y= 36 mL, and Z = 6.4 mm equates to 0.521 1/millimeters which is less than 1.5 1/millimeters when V = 1.5 1/millimeters.
Claim(s) 9 and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wei in view of Rodriguez San Juan et al. (US 2011/0186537 A1; hereinafter referred to as “Rodriguez”).
With regards to claim 9, the system of Wei discloses the claimed invention of claim 1, however, Wei is silent with regards to wherein a total length of the barrel is 40 mm or more and/or 80 mm or less.
Nonetheless Rodriguez, which is within the analogous art of syringes (see [0003]), teaches a total length of the barrel (12) (see [0056]) is 40 mm or more and/or 80 mm or less (see [0065] “For example, for a one ml volume syringe barrel, the inner diameter of the barrel is about 0.25 inches (6.35 mm) and the length is about 2.0 inches (50.8 mm).”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the size of the barrel of the system of Wei in view of a teaching of Rodriguez such that a total length of the barrel is 40 mm or more and/or 80 mm or less. One of ordinary skill in the art would have been motivated to make this modification because Rodriguez teaches the length of the syringe can be of any size desired (see [0056] of Rodriguez). Additionally, in Gardner v. TEC. Syst., Inc., the court held that where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, the claimed device is not patentably distinct from the prior art device. Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 USPQ 232 (1984); MPEP 2144.04(IV)(A).
With regards to claim 10, the system of Wei discloses the claimed invention of claim 1, however, Wei is silent with regards to wherein an inside diameter of the barrel is 5 mm or more and/or 10 mm or less.
However Wei, is silent with regards to an inside diameter of the barrel is 5 mm or more and/or 10 mm or less.
Nonetheless Rodriguez, which is within the analogous art of syringes (see [0003]), teaches an inside diameter of the barrel (12) (see [0065]) is 5 mm or more and/or 10 mm or less. (see [0065] “For example, for a one ml volume syringe barrel, the inner diameter of the barrel is about 0.25 inches (6.35 mm) and the length is about 2.0 inches (50.8 mm).”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the size of the inside diameter of the barrel of the system of Wei in view of a teaching of Rodriguez such that an inside diameter of the barrel is 5 mm or more and/or 10 mm or less. One of ordinary skill in the art would have been motivated to make this modification because Rodriguez teaches the inside diameter of the barrel of the syringe can be of any size desired (see [0056] of Rodriguez). Additionally, in Gardner v. TEC. Syst., Inc., the court held that where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, the claimed device is not patentably distinct from the prior art device. Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 USPQ 232 (1984); MPEP 2144.04(IV)(A).
Claim(s) 11 – 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wei in view of Fiedler (US 2018/0326126 A1).
With regards to claim 11, Wei discloses the claimed invention of claim 1, however Wei is silent with regards to wherein the liquid pharmaceutical composition comprises an additive.
Nonetheless Fiedler, which is within the analogous art of pre-filled plastic syringes containing a pharmaceutical composition (see abstract and title), teaches the liquid pharmaceutical composition comprises an additive (see [0074] “The present commercial aflibercept formulation contains sodium phosphate, sodium chloride, polysorbate 20, sucrose and water for injection and is supplied in a concentration of 40 mg/ml. In particular, it contains 40 mg/ml Aflibercept, 10 mM sodium phosphate buffer, 40 mM NaCl, 0.03% polysorbate 20, 5% sucrose; and water for injection. An alternative aflibercept formulation may contain a histidine buffer, sodium chloride, polysorbate 20, sucrose and water for injection and is supplied in a concentration of 40 mg/ml.” wherein the additive is NaCl).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the liquid pharmaceutical composition of the system of Wei in view of a teaching of Fiedler such that the liquid pharmaceutical composition comprises an additive. One of ordinary skill in the art would have been motivated to make this modification because NaCl increases the solubility, stabilization, and pH regulation of drug formulation while also serving as a carrier for drugs in the pharmaceutical process. Here, NaCl could be used to increase the solubility of certain drugs within the pharmaceutical composition. NaCl could also be used to act as a stabilizer by regulating the osmotic pressure of drugs. NaCl also adjusts the pH of the drug formulations maintaining the drug formulations within the appropriate range for stability and effectiveness. Finally, NaCl serves as a carrier for drugs in the pharmaceutical process which provides stability and aiding in precise dosing and dispersion. Each of these rationales provide a reason for incorporating the additive of NaCl in the liquid pharmaceutical composition.
The system of Wei modified in view of a teaching of Fiedler will hereinafter be referred to as the system of Wei and Fiedler.
With regards to claim 12, the system of Wei and Fiedler teaches the claimed invention of claim 11, however Wei is silent with regards to wherein the additive is selected from the group consisting of salt, sugar, lipid, and acid.
Nonetheless Fiedler, which is within the analogous art of pre-filled plastic syringes containing a pharmaceutical composition (see abstract and title), teaches the additive is selected from the group consisting of salt, sugar, lipid, and acid (see [0074] “The present commercial aflibercept formulation contains sodium phosphate, sodium chloride, polysorbate 20, sucrose and water for injection and is supplied in a concentration of 40 mg/ml. In particular, it contains 40 mg/ml Aflibercept, 10 mM sodium phosphate buffer, 40 mM NaCl, 0.03% polysorbate 20, 5% sucrose; and water for injection. An alternative aflibercept formulation may contain a histidine buffer, sodium chloride, polysorbate 20, sucrose and water for injection and is supplied in a concentration of 40 mg/ml.” wherein the additive is NaCl which is a salt).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the liquid pharmaceutical composition of the system of Wei and Fiedler in view of a further teaching of Fiedler such that the additive is selected from the group consisting of salt, sugar, lipid, and acid. One of ordinary skill in the art would have been motivated to make this modification because NaCl increases the solubility, stabilization, and pH regulation of drug formulation while also serving as a carrier for drugs in the pharmaceutical process. Here, NaCl could be used to increase the solubility of certain drugs within the pharmaceutical composition. NaCl could also be used to act as a stabilizer by regulating the osmotic pressure of drugs. NaCl also adjusts the pH of the drug formulations maintaining the drug formulations within the appropriate range for stability and effectiveness. Finally, NaCl serves as a carrier for drugs in the pharmaceutical process which provides stability and aiding in precise dosing and dispersion. Each of these rationales provide a reason for incorporating the additive of NaCl in the liquid pharmaceutical composition.
With regards to claim 13, the system of Wei and Fiedler teaches the claimed invention of claim 12, however Wei is silent with regards to wherein the additive is selected from the group consisting of NaCl, KCl, sucrose, sodium acetate, acetic acid, ((4-hydroxybutyl)azanediyl)bis(hexan-6,1-diyl)bis(2-hexyldecanoat), 2[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1,2-Distearoyl-sn-glycero-3-phosphocholine, SM(sphyngomyelin)-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC], cholesterol, polyethylene glycol (PEG), H3PO4, XH2PO4, X2HPO4 and X3PO4, wherein X is Na and/or K.
Nonetheless Fiedler, which is within the analogous art of pre-filled plastic syringes containing a pharmaceutical composition (see abstract and title), teaches the additive is NaCl (see [0074] “The present commercial aflibercept formulation contains sodium phosphate, sodium chloride, polysorbate 20, sucrose and water for injection and is supplied in a concentration of 40 mg/ml. In particular, it contains 40 mg/ml Aflibercept, 10 mM sodium phosphate buffer, 40 mM NaCl, 0.03% polysorbate 20, 5% sucrose; and water for injection. An alternative aflibercept formulation may contain a histidine buffer, sodium chloride, polysorbate 20, sucrose and water for injection and is supplied in a concentration of 40 mg/ml.” wherein the additive is NaCl).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the additive of the pharmaceutical composition of the system of Wei and Fiedler in view of a further teaching of Fiedler such that the additive is NaCl. One of ordinary skill in the art would have been motivated to make this modification because NaCl increases the solubility, stabilization, and pH regulation of drug formulation while also serving as a carrier for drugs in the pharmaceutical process. Here, NaCl could be used to increase the solubility of certain drugs within the pharmaceutical composition. NaCl could also be used to act as a stabilizer by regulating the osmotic pressure of drugs. NaCl also adjusts the pH of the drug formulations maintaining the drug formulations within the appropriate range for stability and effectiveness. Finally, NaCl serves as a carrier for drugs in the pharmaceutical process which provides stability and aiding in precise dosing and dispersion. Each of these rationales provide a reason for incorporating the additive of NaCl in the liquid pharmaceutical composition.
With regards to claim 14, the system of Wei and Fiedler teaches the claimed invention of claim 11, however Wei is silent with regards to wherein a concentration of the additive is 0.01 mol/l or more and/or 1 mol/l or less.
Nonetheless Fiedler, which is within the analogous art of pre-filled plastic syringes containing a pharmaceutical composition (see abstract and title), teaches wherein a concentration of the additive is 0.01 mol/l or more and/or 1 mol/l or less (see [0074] “The present commercial aflibercept formulation contains sodium phosphate, sodium chloride, polysorbate 20, sucrose and water for injection and is supplied in a concentration of 40 mg/ml. In particular, it contains 40 mg/ml Aflibercept, 10 mM sodium phosphate buffer, 40 mM NaCl, 0.03% polysorbate 20, 5% sucrose; and water for injection. An alternative aflibercept formulation may contain a histidine buffer, sodium chloride, polysorbate 20, sucrose and water for injection and is supplied in a concentration of 40 mg/ml.” Wherein the additive is the 40 millimoles/L equates to 0.04 moles/L of NaCl).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the concentration of the additive within the pharmaceutical composition of the system of Wei and Fielder in view of a further teaching of Fielder such that a concentration of the additive is 0.01 mol/l or more and/or 1 mol/l or less. One of ordinary skill in the art would have been motivated to make this modification because NaCl increases the solubility, stabilization, and pH regulation of drug formulation while also serving as a carrier for drugs in the pharmaceutical process. Here, NaCl could be used to increase the solubility of certain drugs within the pharmaceutical composition. NaCl could also be used to act as a stabilizer by regulating the osmotic pressure of drugs. NaCl also adjusts the pH of the drug formulations maintaining the drug formulations within the appropriate range for stability and effectiveness. Finally, NaCl serves as a carrier for drugs in the pharmaceutical process which provides stability and aiding in precise dosing and dispersion. Each of these rationales provide a reason for incorporating the additive of NaCl in the liquid pharmaceutical composition.
With regards to claim 15, the system of Wei and Fiedler teaches the claimed invention of claim 11, however Wei is silent with regards to wherein a concentration of the additive is 1 g/l or more and/or 300 g/l or less.
Nonetheless Fiedler, which is within the analogous art of pre-filled plastic syringes containing a pharmaceutical composition (see abstract and title), teaches a concentration of the additive is 1 g/l or more and/or 300 g/l or less (see [0074] “The present commercial aflibercept formulation contains sodium phosphate, sodium chloride, polysorbate 20, sucrose and water for injection and is supplied in a concentration of 40 mg/ml. In particular, it contains 40 mg/ml Aflibercept, 10 mM sodium phosphate buffer, 40 mM NaCl, 0.03% polysorbate 20, 5% sucrose; and water for injection. An alternative aflibercept formulation may contain a histidine buffer, sodium chloride, polysorbate 20, sucrose and water for injection and is supplied in a concentration of 40 mg/ml.” Wherein the additive is the 40 millimoles/L which equates to 2.34 g/L of NaCl).
40 mM/L = 0.04 mol/L
Molar mass of NaCl = 58.443 g/mol
0.04 mol/L * 58.443 g/mol = 2.34 g/L of NaCl
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the concentration of the additive of the system of Wei and Fiedler in view of a further teaching of Fiedler such that a concentration of the additive is 1 g/l or more and/or 300 g/l or less. One of ordinary skill in the art would have been motivated to make this modification because NaCl increases the solubility, stabilization, and pH regulation of drug formulation while also serving as a carrier for drugs in the pharmaceutical process. Here, NaCl could be used to increase the solubility of certain drugs within the pharmaceutical composition. NaCl could also be used to act as a stabilizer by regulating the osmotic pressure of drugs. NaCl also adjusts the pH of the drug formulations maintaining the drug formulations within the appropriate range for stability and effectiveness. Finally, NaCl serves as a carrier for drugs in the pharmaceutical process which provides stability and aiding in precise dosing and dispersion. Each of these rationales provide a reason for incorporating the additive of NaCl in the liquid pharmaceutical composition.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wei and Engelund et al. (US 2021/0252111 A1; hereinafter referred to as “Engelund”).
With regards to claim 16, the system of Wei discloses the claimed invention of claim 1, however, Wei is silent with regards to wherein more than 80% (w/w) of the liquid pharmaceutical composition is H2O and/or the gas comprises or is air, CO2, N2, Ar, and/or O2.
Nonetheless Engelund, which is within the analogous art of pharmaceutical compositions (see [0006]), teaches wherein more than 80% (w/w) of the liquid pharmaceutical composition is H2O (see [0018] “In some embodiments the liquid pharmaceutical composition is an aqueous solution comprising at least 60% w/w water, such as at least 70% w/w water or at least 80% w/w water. In some embodiments the liquid pharmaceutical composition is an aqueous solution comprising at least 97% w/w water, such as at least 98% w/w water. In some embodiments the liquid pharmaceutical composition is an aqueous solution comprising 97-99% w/w water.”) and/or the gas comprises or is air, CO2, N2, Ar, and/or O2.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the amount of H2O in the pharmaceutical composition of the system of Wei in view of a teaching of Englund such that more than 80% (w/w) of the liquid pharmaceutical composition is H2O. One of ordinary skill in the art would have been motivated to make this modification because adjusting the amount of water in a pharmaceutical composition because the amount of water within a pharmaceutical composition affects the stability and quality control of the pharmaceutical composition. For example, water influences the stability of compounded preparations, affecting chemical degradation, microbial growth, and potency loss. Similarly, the amount of water ensures the safety, efficacy, and longevity of the pharmaceutical composition.
Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wei in view of Moser et al. (US 2020/0246555 A1; hereinafter referred to as “Moser”).
With regards to claim 17, the system of Wei discloses the claimed invention of claim 1, however, Wei is silent with regards to wherein a total length of the container, measured along an axial extension of the container, is 30 mm or more and/or 200 mm or less.
Nonetheless Moser, which is within the analogous art of syringe body (see abstract and title), teaches (see Fig. 4) a total length of the container, measured along an axial extension of the container, is 30 mm or more and/or 200 mm or less (see Fig. 4 and [0080] “The syringe body 12 in the illustrated embodiment has a total length L.sub.SK of 80.0 mm.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the total length of the container of the system of Wei in view of a teaching of Moser such that a total length of the container, measured along an axial extension of the container, is 30 mm or more and/or 200 mm or less. One of ordinary skill in the art would have been motivated to make this modification because Moser teaches the syringe body can have a total length of 80 mm. Additionally, in Gardner v. TEC. Syst., Inc., the court held that where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, the claimed device is not patentably distinct from the prior art device. Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 USPQ 232 (1984); MPEP 2144.04(IV)(A).
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wei.
With regards to claim 19, Wei discloses the claimed invention of claim 1, however, this embodiment of Wei, shown in Figs. 1 – 6, is silent with regards to wherein the stopper comprises at least one inner recess.
Nonetheless a second embodiment of Wei (see Figs. 7 – 8) teach the stopper (109) comprises at least one inner recess (see [0023] “the rear surface of syringe piston 109 may include a substantially central recess”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the stopper of the system of the first embodiment of Wei in view of a teaching of the second embodiment of Wei such that the stopper comprises at least one inner recess. One of ordinary skill in the art would have been motivated to make this modification because Wei teaches that this recess allows for the threadable connection of the push rod with the piston. A person having ordinary skill in the art would recognize that attaching the piston to the push rod via a threadable connection is beneficial because it provides a secure and stable interface between the components.
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wei in view of Vukmirovic et al. (US 2005/0238720 A1; hereinafter referred to as “Vukmirovic”).
With regards to claim 20, Wei discloses the claimed invention of claim 1, and Wei further discloses (see Figs. 1 – 6) wherein the barrel (103) comprises a polymer (see [0020] “a pre-filled syringe barrel 103, as medication container, can be made of either glass or plastic material” wherein plastic is an example of a polymer).
However Wei is silent with regards to the closure comprises a brombutyl rubber.
Nonetheless Vukmirovic, which is within the analogous art of pharmaceutical compositions (se [0100]), teaches the closure comprises a brombutyl rubber (see [0100] “elastic closures from brombutyl rubber”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to modify the material of the closure of the system of Wei in view of a teaching of Vukmirovic such that the closure comprises a brombutyl rubber. One of ordinary skill in the art would have been motivated to make this modification because Vukmirovic teaches that the elastic closure can comprise brombutyl rubber (see [0100] of Vukmirovic). Additionally, it would have been obvious to one having ordinary skill in the art at the time the invention was made to modify the rubber of the closure of Wei in view of a teaching of Vukmirovic, since it has been held to be within the general skill of a worker in the art to select a known material on the basis of its suitability for the intended use as a matter of obvious design choice. In re Leshin, 277 F.2d 197, 125 USPQ 416 (CCPA 1960); MPEP 2144.07.
Conclusion
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/ROBERT F ALLEN/Examiner, Art Unit 3783
/WILLIAM R CARPENTER/Primary Examiner, Art Unit 3783 02/18/2026