OPHTHALMIC VISCOELASTIC COMPOSITIONS

DETAILED ACTION Status of Application The response filed 08/11/2026 has been received, entered and carefully considered. The response affects the instant application accordingly: Claims 1, 10-11, 13-14 have been amended. Claims 2, 15 has been cancelled. Claims 21-22 have been added. Claims 1, 3-14, 16-22 are pending in the case. Claims 1, 3-14, 16-22 are present for examination. Applicant had previously elected the species of hyaluronic acid for the examination which was expanded to also include hyaluronic acid with cellulose polymers. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . All grounds not addressed in the action are withdrawn or moot as a result of amendment. New grounds of rejection are set forth in the current office action as a result of amendment. New Grounds of Rejection Due to the amendment of the claims the new grounds of rejection are applied: 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. Claims 1, 3-14, 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Bucolo et al. (U.S. Pat. Pub. 2010/0036387) in view of Welch et al. (U.S. Pat. 2017/0014487). Rejection: Bucolo et al. teaches ocular surgery such as a cataract lens replacement comprising providing an opening/passage through the sclera into the anterior chamber of the eye (anterior capsulotomy), a portion of the aqueous humor is removed from the anterior chamber, a viscoelastic composition is injected into the anterior chamber (first application), the lens in the capsular bag is removed (i.e. phacoemulsification), the viscoelastic composition is injected into the capsular bag (which is known to be within the posterior chamber, second application/composition) and an intraocular lens is placed into the capsular bag [18-19, 90-100]. The viscoelastic composition contains tris[hydroxymethyl]aminomethane which is a known ingredient in buffer systems and about 0.01-about 20% w/v of a viscoelastic polymer like hyaluronic acid [13, 15] including about 0.5-about 3% w/v (Table 1, [48, 59]). The viscoelastic polymer like hyaluronic acid has an average molecular weight of about 20kD to about 5,000kD [42]. The tris[hydroxymethyl]aminomethane can be about 0.1-about 500mM and about 1mM to about 100mM with a preferred concentration from around 0.5mM-about 25mM (about 0.006-0.30%w/v, Table 1, [36, 59], abstract, claims 10-11). The composition can also comprises a polyol like mannitol, sorbitol, and mixtures thereof ([16] also known as tonicity/osmolyte agents), and be buffered to pH of about 5-about 8 including a range of 6.9-7.5 ([58], Table 1).Bucolo et al. also teaches examples with about 2% hyaluronic acid with a molecular weight of 1.98X10 6 (1,980,000 - falling within about 500,000-about 1,900,000, and about 2,000,000-about 5,000,000), with sorbitol and 20mM tris (about 0.24%w/v) and water (see Example 1-2). Bucolo also demonstrates that one can add phosphate buffer to the solution (Example 9, see full document specifically areas cited). Bucolo et al. does not expressly teach the inclusion of phosphate buffer with the hyaluronic acid and tris[hydroxymethyl]aminomethane for the viscoelastic composition used in the ocular/cataract surgery, but does expressly teach the inclusion of buffers like tris[hydroxymethyl]aminomethane and that the pH of the viscoelastic composition is to be from about 5-about 8 including a range of 6.9-7.5. Welch et al. teaches that for the adjustment of pH from 4.0-8.0, preferably about 6.5-7.8; buffers may be especially useful and suitable buffers include TRIS (tris[hydroxymethyl]aminomethane), phosphate buffers (including combinations of Na2HPO4 (sodium hydrogen phosphate monobasic), NaH2PO4 (sodium hydrogen phosphate dibasic) and KH2PO4 (potassium hydrogen phosphate dibasic)), and mixtures thereof ranging from about 0.05-2.5%wt. preferably about 0.1-1.5%wt. [97]. Wherein it would be obvious to one of skill in the art before the effective filing date of the claimed invention to incorporate a phosphate buffer as suggested by Welch et al. and produce the claimed invention; as Bucolo et a. teaches that the viscoelastic composition includes tris[hydroxymethyl]aminomethane and have a pH of about 5-about 8, wherein it is prima facie obvious to incorporate known buffer mixtures like phosphates such as sodium hydrogen phosphate monobasic, with TRIS for their known purposes to attain the taught pH of about 5-about 8 like 6.9-7.5 and including the preferred pH of 6.5-7.8 with a reasonable expectation of success absent evidence of criticality for the specific buffers. It would also be prima facie obvious to optimize the amount of phosphate buffer as Welch et al. teaches that buffers are generally used at about 0.1-1.5% and Bucolo et al. teaches the TRIS to be from about 0.1mM to about 500mM such as 20mM (about 0.24%w/v) wherein it would be prima facie obvious to optimize the amount of phosphate buffer within the taught range in conjunction with the TRIS amount and arrive at the claimed values as a means of attaining the desired therapeutic profile with a reasonable expectation of success. Response to Arguments: Applicant's arguments center on the assertions that Bucolo does not teach the inclusion of the phosphate buffer with the hyaluronic acid and Tris for the viscoelastic composition used in the ocular/cataract surgery, that the Examiner has no basis in the Bucolo reference for adding a second buffer to the composition much less the phosphate buffer in the claimed range, that Welch fails to cure the deficiencies of Bucolo. This is fully considered but not persuasive. The assertion that Bucolo does not include the phosphate buffer with the hyaluronic acid and Tris for the viscoelastic composition used in the ocular/cataract surgery, and that the Examiner has no basis in the Bucolo reference for adding a second buffer to the composition much less the phosphate buffer in the claimed range - is an argument that the prior art reference must be a single reference containing all the claimed elements and have a singular teaching to be applicable for obviousness which is not the standard for obviousness. Obviousness is not restricted to a single reference as obviousness may be to a combination of references as addressed in the rejection above. Welch et al. establishes that pH can be adjusted from 4.0-8.0, preferably about 6.5-7.8; with suitable buffers including tris[hydroxymethyl]aminomethane, phosphate buffers, and mixtures thereof ranging from about 0.05-2.5%wt. preferably about 0.1-1.5%wt.; wherein it is prima facie obvious to incorporate known buffer mixtures like phosphates such as sodium hydrogen phosphate monobasic, with TRIS for their known purposes to attain the taught pH of about 5-about 8 including the range of 6.9-7.5 taught with a reasonable expectation of success absent evidence of criticality for the specific buffers. It would be prima facie obvious to optimize the amount of phosphate buffer within the taught range in conjunction with the TRIS amount and arrive at the claimed values as a means of attaining the desired therapeutic profile with a reasonable expectation of success. Applicant’s remaining argument to Welch is against the reference individually, and one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Accordingly, the rejection stands. Claims 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Bucolo et al. (U.S. Pat. Pub. 2010/0036387) in view of Welch et al. (U.S. Pat. 2017/0014487) as applied to claims 1, 3-14, 16-20 above, further in view of DuoVisc (How Supplied) and Environmental monitor (What is Air Temperature?- How is Air Temperature measured?) Rejection: The teachings of Bucolo et al. in view of Welch et al. are addressed above. Bucolo et al. in view of Welch et al. does not expressly recite the temperature the viscoelastic compositions are stored and used at but does teach the use of viscoelastics in ocular surgery like cataract surgery and to have a preferred pH of 6.5-7.8. DuoVisc teaches that it is known that viscoelastics be store in the refrigerator from 2-8oC and then should be allowed to attain room temperature prior to use (Page 1-How Supplied). Environmental monitor establishes that room temperature is typically considered to be 20-25oC (How is Air Temperature measured?). Wherein it would be obvious to one of skill in the art before the effective filing date of the claimed invention to store the viscoelastic compositions in the refrigerator from 4oC and then have it attain room temperature of about 22oC prior to use as suggested by DuoVisc and Environmental monitor and produce the claimed invention. As it is prima facie obvious to store and use the viscoelastics in its conventional means including storing it in the refrigerator at 2-8oC and then allowed to attain room temperature from 20-25oC with a reasonable expectation of success. It is also prima facie obvious to optimize the storage and room temperature within the known ranges with a reasonable expectation of success absent evidence of criticality for the claimed values. Conclusion Claims 1, 3-14, 16-22 are rejected. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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. Any inquiry concerning this communication or earlier communications from the examiner should be directed to GIGI GEORGIANA HUANG whose telephone number is (571)272-9073. The examiner can normally be reached Monday-Thursday 9:00-5:00pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /GIGI G HUANG/Primary Examiner, Art Unit 1613