DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the AIA first to file provisions. 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 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.
Application Status
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 7/20/2026 has been entered.
Claims 1, 4-5, 7, 10, 12, 16, 19-22, 25, 27, and 30 are currently pending.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 4-5, 7, 10, 12, 16, 19-22, 25, 27, and 30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Regarding claims 1, 10, 19, and 27:
Claims 1, 10, 19, and 27 each recite variations of “wherein a process performance index (Cpk) for a filling process of the vial throughout a fill cycle exceeds a minimum value”. This limitation is indefinite at least for the following reasons:
The claims are drawn to methods for filling a vial. In view of the Le declaration and Mahapatra reference, in order to calculate Cpk, a mean value and standard deviation for multiple preceding filling cycles would be required, meaning the method for filling a vial, as currently claimed, would not be possible as a stand-alone filling method, rendering the claim indefinite.
The limitation of Cpk exceeding “a minimum value” is indefinite because it is unclear what the minimum value is, and how it can be obtained, especially for a single filling cycle.
The limitation of Cpk exceeding a minimum value “throughout a fill cycle” is indefinite because Cpk is a value that can only be obtained upon completion of the filling method, and not throughout.
The limitation “a filling process of the vial throughout a fill cycle” is indefinite because it is unclear how the “a filling process” and “a fill cycle” differ, and whether they are the same as, or different from the claimed “filling the vial with a drug product” step in the method.
Claims dependent on the above claims are therefore also rejected as being dependent on a rejected claim.
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.
Claims 1, 5, 7, 27, and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nishizawa US 2021/0229848.
Regarding claim 1:
Nishizawa teaches a method of filling a vial ([0156]), the method comprising: providing a pump (pumps A, B) corresponding to a vial; setting a no adjustment limit for a fill weight of the vial to T1, T1 being at or in a range of about 2% more or less than a fill weight of a target fill weight TO ([0156] discusses setting the fill amount to a target amount; e.g., 0.05 mL to 100 mL for a vial and/or a syringe); and filling the vial with a drug product via the pump (e.g., [0002]; claim 7), wherein the drug product has one or more of the following characteristics: (a) a density in a range of about 1.0-1.2 g/cm3; (b) a viscosity in a range of about 1.0-10.0 cP; and (c) a surface tension in a range of about 40.0 - 72.7 mN/m (e.g., see “Formulation B” in [0222]).
Nishizawa does not expressly teach the wherein clause “wherein a process performance index (Cpk) for a filling process of the vial throughout a fill cycle exceeds a minimum value”.
However, given that Cpk is a result of the process itself, and it has been held that such a clause “in a method claim is not given weight when it simply expresses the intended result of a process step positively recited” (see MPEP 2111.04 I.), the clause is not deemed sufficient to differentiate the method from the method taught by Nishizawa. Alternatively, the minimum value can be taken as an arbitrarily small value, such that any non-negligible Cpk value will exceed the chosen minimum.
Regarding claim 5:
Nishizawa teaches the method of claim 1, as discussed above, wherein providing a pump corresponding to a vial comprises providing a fill set including a peristaltic pump filling assembly ([0271], [0272]) having a needle with an outer diameter of about 3.0mm ([0157], “2.6 mm to 3.6 mm” is interpreted as “about 3.0 mm”).
Regarding claim 7:
Nishizawa teaches the method of claim 1, as discussed above, wherein the drug product has a density in a range of about 1.0-1.2 g/cm3; a viscosity in a range of about 1.0-10.0 cP, and a surface tension in a range of about 40.0-- 72.7 mN/m (e.g., “Formulation B” in [0222]).
Regarding claim 27:
Nishizawa teaches a method of filling a vial, the method comprising: providing a pump corresponding to a vial (e.g., pumps A, B; [0271], [0272]); setting a no adjustment limit for a fill weight of the vial to any value within a range of a target fill weight TO and T1, with T1 being at or in a range between the target fill weight TO and T2 ([0156] discusses setting the fill amount to a target amount; e.g., 0.05 mL to 100 mL for a vial and/or a syringe), and filling the vial with a drug product via the pump (e.g., see [0276]-[0280]), wherein filling the vial with a drug product via the pump comprises filling the vial with a drug product including one or more of: (1) a density in a range of about 1.0-1.2 g/cm3; and/or (2) a viscosity in a range of about 1.0- 10.0 cP: and/or (3) a surface tension in a range of about 40.0-72.7 mN/m (e.g., see “Formulation B” in [0222]).
Nishizawa does not expressly teach the wherein clause “wherein a process performance index (Cpk) for a filling process of the at least one container throuqhout at least one fill cycle exceeds a minimum value”.
However, given that Cpk is a result of the process itself, and it has been held that such a clause “in a method claim is not given weight when it simply expresses the intended result of a process step positively recited” (see MPEP 2111.04 I.), the clause is not deemed sufficient to differentiate the method from the method taught by Nishizawa. Alternatively, the minimum value can be taken as an arbitrarily small value, such that any non-negligible Cpk value will exceed the chosen minimum.
Regarding claim 30:
Nishizawa teaches the method of claim 27, as discussed above, wherein providing a pump corresponding to a vial comprises providing a fill set including a peristaltic pump filling assembly ([0271], [0272]) having a needle with an outer diameter of about 3.0mm ([0157], “2.6 mm to 3.6 mm” is interpreted as “about 3.0 mm”).
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 4, 10, 12, 16, 19-22 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Nishizawa, as applied above, and further in view of Husnu et al. US 2016/0199257.
Regarding claim 4:
Nishizawa teaches the method of claim 1, as discussed above, but does not teach wherein providing a pump corresponding to a vial comprises providing a pump corresponding to a vial of a nested syringe and vial line.
Husnu discloses a related filling method, teaching “Although described herein as having one pump 200 or one bulk product vial 100, for example, the system may encompass multiple pumps feeding multiple fluid pathways for dispensing multiple different products without cross contamination. The potential exposure of technicians may be further reduced, as the necessity to enter the shielded environment in order to change out disposable components of the system 10 between batches (radiation safety hazard) may be further reduced.” ([0084]).
It would have been obvious to a person having ordinary skill in the art, at the effective filing date of the invention, to modify the method of Nishikzawa, by providing a pump or multiple pumps corresponding to vials of a nested syringe and vial line, as taught by Husnu, since this would be useful in reducing associated operating safety hazards.
Regarding claim 10:
Nishizawa teaches a method of filling a plurality of vials, the method comprising: providing a plurality of pumps (e.g., pumps A, B; [0271], [0272]) corresponding to a plurality of vials; setting a no adjustment limit for a fill weight of each vial to T1, with T1 being at or in a range of about 2% more or less than a fill weight of a target fill weight TO ([0156] discusses setting the fill amount to a target amount; e.g., 0.05 mL to 100 mL for a vial and/or a syringe); and filling each vial of the plurality of vials with a drug product via a corresponding pump (e.g., see [0276]-[0280]), wherein the drug product has one or more of the following characteristics: (1) a density in a range of about 1.0-1.2 g/cm3; (2) a viscosity in a range of about 1.0-10.0 cP; and/or (3) a surface tension in a range of about 40.0-72.7 mN/m (e.g., see “Formulation B” in [0222]).
Nishizawa does not teach the vials being of a nested syringe and vial line.
Husnu discloses a related filling method, teaching “Although described herein as having one pump 200 or one bulk product vial 100, for example, the system may encompass multiple pumps feeding multiple fluid pathways for dispensing multiple different products without cross contamination. The potential exposure of technicians may be further reduced, as the necessity to enter the shielded environment in order to change out disposable components of the system 10 between batches (radiation safety hazard) may be further reduced.” ([0084]).
It would have been obvious to a person having ordinary skill in the art, at the effective filing date of the invention, to modify the method of Nishikzawa, by providing a pump or multiple pumps corresponding to vials of a nested syringe and vial line, as taught by Husnu, since this would be useful in reducing associated operating safety hazards.
Nishizawa does not expressly teach the wherein clause “wherein a process performance index (Cpk) for a filling process of each vial of the plurality of vials throughout a fill cycle exceeds a minimum value”.
However, given that Cpk is a result of the process itself, and it has been held that such a clause “in a method claim is not given weight when it simply expresses the intended result of a process step positively recited” (see MPEP 2111.04 I.), the clause is not deemed sufficient to differentiate the method from the method taught by Nishizawa. Alternatively, the minimum value can be taken as an arbitrarily small value, such that any non-negligible Cpk value will exceed the chosen minimum.
Regarding claim 12:
The combination of Nishizawa and Husnu teaches the method of claim 10, as discussed above, wherein filling each vial of the plurality of vials with a drug product via a corresponding pump of the plurality of pumps comprises filling each vial of the plurality of vials with a monoclonal antibodies formulation drug product (Nishizawa, e.g., see “Formulation B” in [0222]).
Regarding claim 16:
The combination of Nishizawa and Husnu teaches the method of claim 10, as discussed above, wherein the drug product has a density in a range of about 1.0-1.2 g/cm3; a viscosity in a range of about 1.0-10.0 cP; and a surface tension in a range of about 40.0-72.7 mN/m (e.g., see “Formulation B” in [0222]).
Regarding claim 19:
Nishizawa teaches a method of optimizing a filling recipe, the method comprising: providing at least one pump (e.g., pumps A, B; [0271], [0272]) in an offline manufacturing system corresponding to at least one container ([0215]);
setting a no adjustment limit for a fill weight of the container to T1, with T1 being at or in a range of about 2% more or less than a fill weight of a target fill weight TO ([0156] discusses setting the fill amount to a target amount; e.g., 0.05 mL to 100 mL for a vial and/or a syringe);
filling the at least one container with a drug product having one or more of: (a) a density in a range of about 1.0-1.2 g/cm3; (b) a viscosity in a range of about 1.0-10.0 cP; and (c) a surface tension in a range of about 40.0-72.7 mN/m (e.g., see “Formulation B” in [0222]) via the at least one pump (e.g., see [0276]-[0280]); and finalizing a filling recipe using data from fill cycles of the drug product using the at least one pump in the offline manufacturing system ([0156] discusses finalized filling amount recipes for various vessels).
Nishizawa does not teach the vials being of a nested syringe and vial line.
Husnu discloses a related filling method, teaching “Although described herein as having one pump 200 or one bulk product vial 100, for example, the system may encompass multiple pumps feeding multiple fluid pathways for dispensing multiple different products without cross contamination. The potential exposure of technicians may be further reduced, as the necessity to enter the shielded environment in order to change out disposable components of the system 10 between batches (radiation safety hazard) may be further reduced.” ([0084]).
It would have been obvious to a person having ordinary skill in the art, at the effective filing date of the invention, to modify the method of Nishikzawa, by providing a pump or multiple pumps corresponding to vials of a nested syringe and vial line, as taught by Husnu, since this would be useful in reducing associated operating safety hazards.
Nishizawa does not expressly teach the wherein clause “wherein a process performance index (Cpk) for a filling process of the at least one container throughout at least one fill cycle exceeds a minimum value”.
However, given that Cpk is a result of the process itself, and it has been held that such a clause “in a method claim is not given weight when it simply expresses the intended result of a process step positively recited” (see MPEP 2111.04 I.), the clause is not deemed sufficient to differentiate the method from the method taught by Nishizawa. Alternatively, the minimum value can be taken as an arbitrarily small value, such that any non-negligible Cpk value will exceed the chosen minimum.
Regarding claim 20:
The combination of Nishizawa and Husnu teaches the method of claim 19, as discussed above, further comprising monitoring a performance of the filling recipe in the nested syringe and vial line for the at least one container for each pump in a plurality of pumps in the nested syringe and vial line (Nishizawa, [0138] discusses monitoring performance and calibrating the filling recipe).
Regarding claim 21:
The combination of Nishizawa and Husnu teaches the method of claim 19, as discussed above, wherein the providing at least one pump in an offline manufacturing system corresponding to at least one container comprises providing a first fill set including a pump and a second fill set including a pump, each of the first and second fill sets in the offline manufacturing system, each of the first fill set and the second fill set having a corresponding filling container (i.e., each pump of Husnu can correspond to a fill set).
Regarding claim 22:
The combination of Nishizawa and Husnu teaches the method of claim 19, as discussed above, wherein the drug product includes a monoclonal antibodies (Nishizawa, [0222]).
Response to Arguments
The Le declaration and Mahapatra reference have been carefully considered.
Applicant’s remarks have also been carefully considered but are not found to be persuasive. As detailed in the 112(b) indefiniteness rejections above, incorporation of the now elucidated Cpk value raises new indefiniteness issues that need to be resolved. See 112(b) rejections above.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DARIUSH SEIF whose telephone number is (408) 918-7542. The examiner can normally be reached on Monday-Friday 9:30 AM-6:00 PM PST.
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/DARIUSH SEIF/Primary Examiner, Art Unit 3731
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