DETAILED ACTION
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-2, 5, 8-10, and 12 are pending and represent all claims currently under consideration.
Response to Amendment
The amendment filed 11/12/2025 has been entered.
Claims 1-2, 5, 9-10, and 12 were amended, and claims 3-4, 6-7, 11, and 13-19 were canceled. No new material was added.
The previous objections and rejections of claims 3-4, 6-7, 11, and 13-14 are moot, because the claims were canceled.
Applicant’s amendments have overcome the previous objections to claim 10 and the specification; the rejections under 35 U.S.C. 112(b) of claims 5 and 12; and the rejections under 35 U.S.C. 102 of claims 1, 5, 8-9, and 12.
Claims 1 and 9 are newly objected to, due to the amendment.
The rejection of claims 1-2, 5, 8-10, and 12 under 35 U.S.C. 103 has been modified to address the amendments and maintained.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Claims 1-2, 5, 8-10, and 12 are considered to have an effective filing date of 07/23/2021.
Information Disclosure Statement
The information disclosure statement filed 11/12/2025 has been considered.
Response to Arguments
Applicant’s arguments, see Remarks (page 6), filed 11/12/2025, with respect to the rejection under 35 U.S.C. 102 over Park have been fully considered and are persuasive due to the amendment. The rejection of claims 1, 5, 8-9, and 12 under 35 U.S.C. 102 has been withdrawn.
Applicant's arguments, see Remarks (pages 6-20), filed 11/12/2025, with respect to the rejection under 35 U.S.C. 103 over Park have been fully considered but they are not persuasive.
Applicant argues that Park does not disclose a composition containing all the features of the claimed invention simultaneously (Remarks, pages 6-7). This argument is not persuasive, because Park teaches all the elements of the invention of the amended claim as discussed in the rejection below.
Applicant argues that it is essential to optimize the formulation conditions to stabilize the protein drug under various environmental conditions, and demonstrates a formulation as claimed has excellent stability compared to formulations of other compositions (Remarks, pages 7-16). Applicant states that Park demonstrates that the optimal pH is 6.0 and the optimal surfactant is when no surfactant is included (Remarks, pages 16-18). This argument is not persuasive, because regarding the surfactant, Park lists the condition comprising 0.01% of polysorbate 20 as one of the five formulations with superior effects (Park, column 12, lines 54-55). Regarding the pH, Park states the formulation shows significantly reduced production of aggregates and fragments (i.e., stability) at pHs of 5.7-6.5 (Park, column 9, lines 38-39), suggesting a pH within this range would be preferable. As stated in the rejection below, Park further states it would be apparent for a person skilled in the art that the specific description is merely a preferred embodiment, and the scope of the present invention is not limited thereto (Park, column 13, lines 13-16). Therefore, it would be obvious to a person skilled in the art to optimize the pH of each formulation within the pH range taught by Park, which includes the claimed pH of 5.8. Further, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. See MPEP § 2123(II). Regarding the assertion that the formulation as claimed has excellent stability compared to formulations of other compositions, evidence of unexpected results must compare the claimed invention with the closest prior art. See MPEP 716.02. In this case, the closest prior art is Park, and the stability data presented in the specification (Remarks, pages 8-14) is not sufficient, because it is not comparative data.
Applicant states that the claimed formulation is stable when stored for long periods under harsh conditions, and states that while Park discloses that the liquid formulations exhibit stability even when stored for long periods under harsh conditions, Park only confirms the change in samples for 7-8 days with a change in the acid peak of at least 20% or more, while the claimed subject matter evaluated the stability for up to 12 months with a change rate of the relative acid peak of 3.9% (Remarks, pages 17-19). This argument is not persuasive, because Park demonstrates HPLC data for various conditions which have as low as a change of 5.5% in the peak referred to by the Applicant as the acid peak (Park, figure 8, sample 4), which is reasonably close to 3.9%. As stated by the Applicant, Park does not test stability over periods longer than 7 days, but there is no evidence provided to suggest that a significant change would be expected between 7 days to 12 months. Therefore, in order to support the Applicant’s assertion that the claimed invention is significantly more stable, the formulation of Park should be compared to the claimed invention over the same time frame.
New Claim Objections
Claims 1 and 9 are objected to because of the following informalities: “pH 5.8” should read “pH of 5.8”. Appropriate correction is required.
Maintained/Modified 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.
Claims 1-2, 5, 8-10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Park (US 9982032 B2) and as evidenced by PubChem (Sucrose, 2025). Park was cited previously by the Examiner. The references were cited previously by the Examiner.
Regarding claim 1, Park teaches a liquid formulation (i.e., composition) comprising 10 to 100 mg/ml of aflibercept, a sugar selected from the group comprising sucrose and trehalose, a surfactant which can be polysorbate 20 (i.e., a polysorbate) in 0-0.1%, and a buffer consisting of a histidine salt having a pH ranging from 5.7 to 6.2 (Park, claim 3). Park further exemplifies a formulation having 0.01% w/v of polysorbate 20 (Park, column 9, line 19, formulation 2), and teaches that the liquid formulation may be used for ophthalmic drug delivery (Park, column 6, lines 24-25), and that the amount of administration is determined by doctors and is an amount effective for the desired therapy (i.e., a therapeutically effective amount; Park, column 8, lines 49-51).
Park teaches an evaluation to find the optimal pH condition (Park, columns 8-9, example 1) and salt concentration (Park, column 11, example 5, formulation 3) for an exemplary formulation. Park teaches a formulation without an additional salt as a preferred alternative to a composition comprising sodium chloride (Park, column 11, example 5, formulation 3). Park further states it would be apparent for a person skilled in the art that the specific description is merely a preferred embodiment, and the scope of the present invention is not limited thereto (Park, column 13, lines 13-16). Therefore, it would be obvious to a person skilled in the art to optimize the pH of each formulation within the pH range taught by Park, which includes the claimed pH of 5.8.
Park is considered to be analogous to the claimed invention, because both Park and the instant invention are in the same field of ophthalmic liquid compositions. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the claimed invention based on the teachings of Park under the meaning of 35 U.S.C. 103.
Regarding claim 2, Park teaches all the elements of the current invention as applied to claim 1. Park exemplifies a formulation comprising the histidine salt buffer in 10 mM (Park, column 10, lines 11-12, formulation 4), which would contain histidine in the same molar amount, and which lies within the claimed range.
Regarding claim 5, Park teaches all the elements of the current invention as applied to claim 1. Park exemplifies a formulation having 5% sucrose (i.e., a sugar; Park, column 10, line 5, formulation 1), and defines the concentration as a percent v/v. As evidenced by PubChem, the density of sucrose is 1.6 g/mL (PubChem, 4.2.8 Density), resulting in a percent w/v of 8% which lies within the claimed range.
Regarding claim 8, Park teaches all the elements of the current invention as applied to claim 1. Park teaches the liquid formulation is suitable for intravitreal injection (Park, claim 4).
Regarding claim 9, Park teaches a formulation (i.e., composition) comprising 10 to 100 mg/ml of aflibercept, a sugar selected from the group comprising sucrose and trehalose, a surfactant, and a buffer consisting of a histidine salt having a pH ranging from 5.7 to 6.2 (Park, claim 3). Park teaches an evaluation to find the optimal pH condition for an exemplary formulation (Park, columns 8-9, example 1), and states it would be apparent for a person skilled in the art that the specific description is merely a preferred embodiment, and the scope of the present invention is not limited thereto (Park, column 13, lines 13-16). Therefore, it would be obvious to a person skilled in the art to optimize the pH of the claimed formulation within the pH range taught by Park, which includes the claimed pH of 5.8.
Park further teaches the liquid formulation show enhanced aflibercept stability (Park, column 6, lines 13-16). Park teaches a surfactant which can be polysorbate 20 (i.e., a polysorbate; Park, claim 3) and exemplifies a formulation having 0.01% w/v polysorbate 20 (Park, column 9, line 19, formulation 2), which lies within the claimed range. Park exemplifies a formulation without an additional salt as a preferred alternative to a composition comprising sodium chloride (Park, column 11, example 5, formulation 3). As above, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the claimed invention based on the teachings of Park under the meaning of 35 U.S.C. 103.
Regarding claim 10, Park teaches all the elements of the current invention as applied to claim 9. As above, Park exemplifies a formulation comprising the histidine salt buffer in 10 mM (Park, column 10, lines 11-12, formulation 4), which would contain histidine in the same molar amount, and which lies within the claimed range.
Regarding claim 12, Park teaches all the elements of the current invention as applied to claim 9. Park exemplifies a formulation having 5% sucrose (i.e., a sugar; Park, column 10, line 5, formulation 1), and defines the concentration as a percent v/v. As evidenced by PubChem, the density of sucrose is 1.6 g/mL (PubChem, 4.2.8 Density), resulting in a percent w/v of 8% which lies within the claimed range.
Conclusion
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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/C.P.J./Examiner, Art Unit 1613
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613