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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 21 August 2025 has been considered by the examiner.
Status of Claims
The amendments and arguments filed 21 August 2025 are acknowledged and have been fully considered. Claims 1-2, 5, 9-11, 15-17, 19-23, 27-29, 31, and 33-37 are currently pending. Claim 20 is amended; claims 3-4, 6-8, 12-14, 18, 24-26, 30, and 32 are cancelled; claims 1-2, 5, 9-11, 15-17, and 19 are withdrawn; claim 37 is new.
Claims 20-23, 27-29, 31, and 33-37 are examined on the merits herein.
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. In particular, the objection to claim 20 being incomplete is withdrawn in view of Applicant’s amendment to the claim. Further, the Double Patenting rejection over Application 17/431,059 (now US Patent No. 12,397,039) is withdrawn in view of Applicant’s persuasive argument regarding the lack of recitation of water content in the claims of Patent. No. ‘039. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 20-23, 27-29, 31, and 33-37 are rejected under 35 U.S.C. 103 as being unpatentable over Günther et al. (US 2016/0159902; of record) in view of Schüle et al. (European Journal of Pharmaceutics and Biopharmaceutics, 2008, Vol. 69, 793-807).
Claim 20 is drawn to a suspension formulation comprising protein particles suspended in a non-aqueous vehicle, made according to a method comprising the steps of:
providing an aqueous solution comprising a protein and a stabilizing agent,
removing the water from said aqueous solution to obtain solid protein particles,
further drying the protein particles obtained in step b) to obtain protein particles comprising a residual water content of less than 0.5 wt%, based on the weight of the particle, and
suspending the protein particles of step c) in a non-aqueous vehicle comprising a semifluorinated alkane,
wherein the protein particle comprises a protein (more specifically an antibody (Applicant’s elected species)) and a stabilizing agent, and wherein the non-aqueous vehicle comprises a semifluorinated alkane.
Günther et al. teach compositions of antibodies based on semifluorinated alkane liquid vehicles (Abstract). Günther et al. further teach in Example 2 (Pars. [0079-0081]) a suspension of bevacizumab particles in F4H5.
As such, Günther et al. teach a suspension formulation comprising protein particles suspended in a non-aqueous vehicle, wherein the protein particle comprises an antibody and the non-aqueous vehicle comprises a semifluorinated alkane.
The suspension of Günther et al. differs from the instantly claimed composition in the following way:
the protein particles of Günther et al. do not comprise a stabilizing agent.
Yet, as to 1: Schüle et al. also teach composition of antibody particles (Abstract). Schüle et al. further teach inclusion of a stabilizer in the protein particles to improve storage stability and decrease aggregation (Abstract).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition of Günther et al. to include a stabilizer as taught by Schüle et al. It would have been obvious to use the known technique of including a stabilizer in antibody particles to improve the similar antibody particles of Günther et al. in the same way, by improving storage stability and decreasing aggregation, with a reasonable expectation of success.
The recitation of the method of producing the suspension formulation is a product-by-process limitation and does not impose further structural limitations on the composition. As discussed in MPEP 2113, "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
In the instant case, the suspension of Günther et al. and Schüle et al. comprises all of the structural elements of the instant claims. As such, the instantly claimed composition is obvious from a product of the prior art, and is unpatentable even though the prior product was made by a different process.
Based on all of the foregoing, claim 20 is rejected as prima facie obvious.
Claim 21 is drawn to a suspension formulation comprising twice dried protein particles comprising a protein (more specifically an antibody (Applicant’s elected species)) and a stabilizing agent, suspended in a non-aqueous liquid vehicle comprising a semifluorinated alkane; wherein the residual water content of the protein particles is less than 0.5 wt%; and wherein at least 90% of the protein particles have a mean diameter of between 1 and 30 µm as determined by laser diffraction.
The recitation of twice dried protein particles is a product-by-process limitation and does not impose further structural limitations on the composition (see MPEP 2113).
As discussed in the rejection of claim 20 above, Günther et al. in view of Schüle et al. teach a suspension formulation comprising protein particles comprising an antibody and a stabilizing agent, suspended in a non-aqueous liquid vehicle comprising a semifluorinated alkane.
Günther et al. further teach the compositions being free from water (Par. [0062]), indicating that the residual water content of the protein particles is less than 0.5 wt%.
Günther et al. do not explicitly teach the size of the protein particles.
However, Schüle et al. teach protein particles having a size between 5.1 and 7.2µm (Abstract), overlapping with the instantly claimed range.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the protein particles of Günther et al. to have a size between 5.1 and 7.2µm. It would have been obvious to do so as Schüle et al. teach the size as being suitable for stable protein particles for delivery of a pharmaceutically active protein, with a reasonable expectation of success.
As such, claim 21 is rejected as prima facie obvious.
Claim 22 is drawn to the suspension of claim 21, wherein the twice dried protein particle is spray-dried and vacuum dried or lyophilized and vacuum dried.
Claim 22 is a product-by-process limitation and does not impose further structural limitations on the composition. As discussed in MPEP 2113, "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
As Günther et al. and Schüle et al. teach the suspension formulation of claim 21, regardless of how it is made, claim 22 is rejected as prima facie obvious.
Claim 23 is drawn to the suspension of claim 21, wherein the stabilizing agent is a saccharide (more specifically sucrose (Applicant’s elected species)).
Schüle et al. further teach the use of sucrose as the stabilizer in the protein particles (Table 6 on pg. 80).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition of Günther et al. and Schüle et al. to comprise sucrose as the stabilizer. It would have been obvious to substitute one stabilizer suitable for use in protein particles with another to obtain the predictable result of a stable protein particle, with a reasonable expectation of success.
As such, claim 23 is rejected as prima facie obvious.
Claim 27 is drawn to the suspension of claim 21 wherein the relative weight ratio of the protein to the stabilizing agent in the protein particles is in the range of 1:1 to 7:3.
Schüle et al. further teach the weight ratio of protein to stabilizing agent ranging from 4:1 to 1:4 (Table 2 on pg. 796), overlapping with the instantly claimed range.
As such, claim 27 is rejected as prima facie obvious.
Claim 28 is drawn to the suspension of claim 21, wherein the semifluorinated alkane is selected from F4H5 and F6H8.
Günther et al. further teach the semifluorinated alkane being F4H5 or F6H8 (Par. [0081]).
As such, claim 28 is rejected as prima facie obvious.
Claim 29 is drawn to the suspension of claim 21, wherein the protein concentration in the suspension is between 2 and 350 mg/mL.
Günther et al. further teach the protein concentration in the suspension being at least 35 mg/mL (Par. [0053]), overlapping with the instantly claimed range.
As such, claim 29 is rejected as prima facie obvious.
Claim 31 is drawn to the suspension of claim 21, wherein the suspension formulation is free of a surfactant.
The suspension of Günther et al. and Schüle et al. comprises the protein particles comprising bevacizumab and sucrose, and a semifluorinated alkane, notably being free of a surfactant. Günther et al. further teach the suspension preferably being free from a surfactant (Par. [0063]).
As such, claim 31 is rejected as prima facie obvious.
Claim 33 is drawn to a kit comprising the suspension formulation of claim 20 and a container adapted for holding said formulation.
Günther et al. further teach storing the protein suspension in amber glass vials (Par. [0081]).
As such, claim 33 is also rejected as prima facie obvious.
Claim 34 is drawn to an administration device comprising the suspension formulation of claim 20, wherein the administration device is adapted for administration of the suspension formulation by injection.
Günther et al. further teach administration of the suspension via subcutaneous, dermal, intramuscular, or locoregional injection (claim 11), which necessarily includes an administration device adapted for injection comprising the suspension.
As such, claim 34 is rejected as prima facie obvious.
Claim 35 is drawn to a kit comprising the suspension formulation of claim 21 and a container adapted for holding said formulation.
Günther et al. further teach storing the protein suspension in amber glass vials (Par. [0081]).
As such, claim 35 is also rejected as prima facie obvious.
Claim 36 is drawn to an administration device comprising the suspension formulation of claim 21, wherein the administration device is adapted for administration of the suspension formulation by injection.
Günther et al. further teach administration of the suspension via subcutaneous, dermal, intramuscular, or locoregional injection (claim 11), which necessarily includes an administration device adapted for injection comprising the suspension.
As such, claim 36 is rejected as prima facie obvious.
Claim 37 is drawn to the suspension formulation of claim 20, wherein step c) drying is vacuum drying conducted at a temperature of between 15-40°C, at a pressure of between 0.01-100 mbar.
Claim 37 is a product-by-process limitation and does not impose further structural limitations on the composition. As discussed in MPEP 2113, "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
As Günther et al. and Schüle et al. teach the suspension formulation of claim 20, regardless of how it is made, claim 37 is rejected as prima facie obvious.
Response to Arguments
Applicant's arguments filed 21 August 2025 have been fully considered but they are not persuasive.
Applicant argues on pg. 9 of the remarks that one of ordinary skill in the art would not combine the teachings of Günther et al. and Schüle et al. as they are in different fields of art and benefits taught in Schüle et al. are not applicable to Günther et al.
This argument is not persuasive. It has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, as both Günther et al. and Schüle et al. are concerned with compositions comprising stable particles of pharmaceutically active proteins, they are considered to be analogous both to the instant claims and to each other.
Further, regarding applicant’s argument that one of ordinary skill in the art would not have a reasonable expectation of success for including a stabilizer in the particles of Günther et al., Günther et al. explicitly teach the addition of stabilizing excipients such as saccharides or polyols pre-lyophilization to support the longer shelf-life of the antibody (Par. [0009]). As such, one of ordinary skill in the art would reasonably expect the addition of a stabilizer as taught by Schüle et al. to the protein particles of Günther et al. to produce a protein suspension formulation with longer shelf-life of the antibody.
Applicant argues on pg. 7-8 of the remarks that there is no teaching in Schüle et al. suggesting that the particles can be dried below 1 wt% water, further arguing on pgs.10-11 of the remarks that the extra drying step taught in Schüle et al. also results in increased aggregation and would offset any improvement derived from decreased water content.
This argument is not persuasive. While Applicant has persuasively argued against the combination of the method of Günther et al. and Schüle et al., the instant claims are drawn to the suspension formulation, not the method by which it is formed. As discussed in MPEP 2113, "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
As Günther et al. and Schüle et al. teach all of the physical limitation of the instant claims as discussed in the rejection of claims under 35 U.S.C. 103 above, the claims are rendered obvious, even though the prior art product was made by a different process.
Applicant may overcome this rejection by demonstrating that there is a nonobvious difference between the claimed product and the prior art product that arises due to the instantly claimed process (See MPEP 2113(II)).
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/PAUL HOERNER/Examiner, Art Unit 1611
/CRAIG D RICCI/Primary Examiner, Art Unit 1611
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