DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Per amendment dated 2/13/26, claims 1-20 are currently pending in the application, with claims 1-3 being withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
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 4-20 are rejected under 35 U.S.C. 103 as being unpatentable over Hiroi et al. (WO 2016/093293 A1) (of record).
At the outset, it is noted that the WIPO publication is relied upon for date purposes while US 10,669,445 B2 is relied upon as its English equivalent in the rejection below.
Regarding claims 4, 8-20, Hiroi teaches a copolymer comprising recurring units obtainable by reacting (A), (B) and (C), in a mol% ratio of (A):(B):(C) at 3- 80:3-80:remainder of (A) and (B), wherein (A) may have following structures (A-2) to (A-4) (read on claimed formula (1)), and (B) may have following structure (B-1) to (B-5) (read on claimed formula (2-1)) (Ab, col. 23, line 17-col. 28, line 62, ref. claims).
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Hiroi teaches acid phosphoxyethyl methacrylate, e.g., Phosmer M/LIGHT ESTER P-1M compound (A-2), acid phosphoxy polyoxypropylene glycol monomethacrylate, e.g., Phosmer PP compound (A-4), and acid phosphoxy polyoxyethylene glycol monomethacrylate, e.g., Phosmer PE compound (A-3), which may include (meth)acrylate functional monomers having two are more functional groups (D) or (E) in the range of 0 to 50 mol% (col. 24, line 17-col. 28, line 28, Examples).
Hiroi further teaches polymerization in a solvent, in the presence of a radical polymerization initiator (col. 30, line 8-col. 31, line 48, Examples) to provide for, preferably, a transparent varnish or a dispersed colloidal varnish, and not causing ununiform gelation or turbid precipitation (col.32, lines 46-53). Disclosed compositions are suitable for forming coating films by diluting with a solvent to a predetermined concentration, said coating films obtainable from a varnish containing the copolymer of (A) and (B) in a solvent, at 0.01 to 20% by mass (col. 30, lines 7-62). The coating films formed on medical substrates and cell culture vessels inhibit adhesion to biological substances (col. 21, lines 16-55).
In disclosed Example 5, Hiroi teaches mixing phosphoxy polyoxyethylene glycol monomethacrylate (Phosmer PE, 8g), 2-(diethylamino)ethyl methacrylate (8.77 g, (reads on (2)) and butyl methacrylate (23.55 g ) are copolymerizing them in a solution.
Hiroi is silent on a method of producing a composition comprising copolymerizing a phosphorus compound of formula (1) in claimed mass%, based on the total mass of the phosphorus-containing compounds in the monomer mixture, with a compound of formula (2), wherein the monomer mixture comprises the compound of formula (1) within the claimed range.
As stated in paragraph 5 above, Hiroi teaches the suitability of phosphoxyethyl methacrylate, acid phosphoxy polyoxypropylene glycol monomethacrylate and acid phosphoxy polyoxyethylene glycol monomethacrylate as monomer (A) (read on formula (1). Hiroi additionally teaches a monomer (B) that overlaps in scope with claimed formula (2), and a copolymer comprising recurring units obtainable by reacting (A), (B) and (C) in a mol% ratio of (A):(B):(C) at 3-80:3-80:remainder of (A) and (B), i.e., (C) may be absent, and given that (meth)acrylate functional monomers having two are more functional groups (D) or (E) may be at 0-50 mol%, (D) and (E) are optional. That is Hiroi’s copolymer may be formed by polymerizing monomers in amounts thereof that overlap the scope of those of the claimed invention. It is noted that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). See MPEP § 2144.05.
Given the teaching in Hiroi on suitable monomers (A) and (B) and broad ranges for the amounts thereof, and the preference for forming transparent or dispersed colloidal varnish, while avoiding ununiform gelation or turbid precipitation, it would have been obvious to one of ordinary skill in the art, as of the effective filing date of the claimed invention, to copolymerize any of the disclosed monomers (A) within the prescribed range, including in an overlapping range, with monomer (B). A skilled artisan would have found it obvious to copolymerize Hiroi’s monomer (A) that is in substantially pure form, in an amount of overlapping scope with monomer (B) so as to provide for copolymers at higher yields, and/or to provide for coatings as purer compositions with improved efficiency in inhibiting adhesion to biological substances, absent evidence of criticality for the claimed purity level of (1).
Additionally, it would have been within the level of ordinary skill in the art to polymerize the monomers, and then add a solvent so as to provide for the desired concentration of the copolymer in the coating composition. Noting that Hiroi also teaches forming coating films on medical substrates, cell culture vessels etc., the recitation “for forming a coating film” in claim 4 is an intended use of the composition.
Regarding claims 5-7, the discussion on Hiroi from preceding paragraphs, as applied to claim 4, are incorporated herein by reference. Noting that a product-by-process limitation is nested in the claimed method step of claim 6, for reasons stated above, it would have been obvious to one of ordinary skill in the art, as of the effective filing date of the claimed invention, to form a coating film on a substrate from a composition comprising a copolymer within the scope of the claimed invention. Additionally, Hiroi teaches the use of coating compositions on medical substrates. Thus, Hiroi’s coating compositions formed from by copolymerizing monomers in pure or substantially form of overlapping scope must inherently be compatible with biomaterials, or would reasonably be expected to be compatible, absent evidence to the contrary.
Response to Arguments
In view of the amendment dated 2/13/26, all rejections set forth in the office action dated 8/14/25 are withdrawn and new grounds of rejections are presented herein above. Applicant’s arguments dated 2/13/26 have been duly considered.
Referring to the Declaration dated Oct. 8, 2024, applicant argues that the present invention provides a simple radical polymerization method of utilizing a polymerizable mixture a monomer mixture that comprises 10-80 mol% of the compound represented by formula (1) having a certain purity (i.e., 85% by mass or more) based on a total mass of phosphorus-containing compounds, allowing for the production of a copolymer-containing varnish with improved cell culture promoting properties, whereas Hiroi’s Phosmer M and Phosmer PE of Examples contain large amounts of impurities, and requires a complicated procedure, that the results are unexpected, and that since Hiroi et al. does not provide any teaching or rationale as to why the level of impurities (e.g., the phosphoric acid or phosphodiester component) in the polymerizable mixture should be reduced.
In response, amended claim 1 requires copolymerizing monomer compound (1) of specified purity level at 10-80 mol%, with monomer compound (2). To that end, for reasons discussed in the rejections of record and herein above, the Hiroi reference teaches a coating composition comprising a copolymer of monomer (A) and (B) of overlapping scope and in overlapping amounts. Hiroi teaches coating compositions comprising such copolymers as being suitable for forming films on medical substrates and cell culture vessels, for inhibiting adhesion to biological substance, and recognizes that difunctional (polymerizable) phosphorus-containing compounds (D) are formed during preparation of monomer (A), such as Phosmer PP, Phosmer PE and Phosmer M. It would have been obvious for a skilled artisan to use such monomers in pure forms to provide for coatings with improved efficiency in inhibiting adhesion to biological substances. "[I]f it is known that some desirable property of a mixture derives in whole or in part from a particular one of its components, or if the prior art would provide a person of ordinary skill in the art with reason to believe that this is so, the purified compound is prima facie obvious over the mixture even without an explicit teaching that the ingredient should be concentrated or purified." Aventis Pharma Deutschland GmbH v. Lupin Ltd., 499 F.3d 1293, 1301 (Fed. Cir. Sept. 11, 2007) (citing In re May, 574 F.2d 1082, 1090–94 (C.C.P.A. 1978). "Ordinarily, one expects a concentrated or purified ingredient to retain the same properties it exhibited in a mixture, and for those properties to be amplified when the ingredient is concentrated or purified; isolation of interesting compounds is a mainstay of the chemist’s art. If it is known how to perform such an isolation, doing so 'is likely the product not of innovation but of ordinary skill and common sense.'" Aventis, 499 F.3d at 1302, citing KSR International Co. v. Teleflex Inc., 550 US 398, 82 USPQ2d 1385 (2007).
Additionally, Hiroi teaches Phosmer compounds as being suitable source for monomer (A), but is silent on a purity level of such compounds. Applicant’s data in the disclosure compares inventive Synthetic Example 1 (based on PPM-5P, purity 95.6% by mass) against comparative Example 1 that comprises Hiroi’s Phosmer M. On the basis that gelation occurs in the comparative Example 1, applicant concludes that Phosmer M and Phsomer PE compounds contain large amounts of impurities and require a complicated procedure (Declaration dated 10/8/24, paragraphs 7-10). However, disclosed Example 5 in Hiroi is drawn to a copolymer formed from Phosmer PE, 2-(diethylamino)ethyl methacrylate, and butyl methacrylate. Per Affidavit dated 10/8/24 (paragraphs 15-16), Phosmer PE comprises 77.6% by mass of acid phosphoxyethyl methacrylate, based on the phosphorus-containing compounds contained in the monomer mixture, i.e., an amount that is close to the claimed lower limit of 85 mass%, and differing only by 9.5%. There is no data on record involving Phosmer PE or superior properties demonstrated against its copolymer. A prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are sufficiently close that one of ordinary skill in the art would expect the ranges to yield products having the same properties. See MPEP 2144.05(I).
Prior to addressing arguments on the asserted unexpected discovery, it is noted that Synthetic Examples 2-4 include 2-methacryloyloxyethyl phosphorylcholine in the polymerization mixtures. For instance, in Synthetic Example 3, the polymerizable mixture includes 2-methacryloyloxyethyl phosphorylcholine (1.25g) and 0.28 g of acid phosphoxypolypropylene glycol monomethacrylate (PPN-5P, 95.6% purity). That is, the mixture includes two different polymerizable phosphorus-containing compounds contained in the monomer mixture, and the calculated mass % of phosphoxypolypropylene glycol monomethacrylate is ~17.6 mass%, based on the phosphorus-containing compounds contained in the monomer mixture, i.e., a value far below the claimed lower limit of “85%”. Clarification is sought on this front.
Regarding arguments on asserted unexpected discovery, Applicant’s attention is drawn to the data in the instant disclosure (TABLEs 1, 2, Reference Example and Comparative Synthetic Examples 1 and 2). It is noted that Comparative Synthetic Examples 1 and 2 that rely on Phosphor M yield white precipitates, as opposed to Synthesis Examples 1-4 (Inv.) providing for a transparent varnish. Additionally, although the coating compositions based on the inventive synthetic examples appear to provide for coatings with improved cell culture promoting property against Ref. Example 1, this comparison is only against a coating film formed from Lipidure-CM5206 of Ref. Example 1.
Thus, as discussed in the preceding paragraphs, there is no proper back-back comparison involving Hiroi’s Phosmer PE, which has a purity level close to the claimed lower limit. Additionally, the formation of a white precipitate (as in comparative Examples 1 and 2) as opposed to a transparent composition (as in Synthesis Examples 1-4) would also depend on the amount of monomer units of formula (1) (claimed at 10-80 mol%), and the type and amount of formula (2) used for polymerization. Even so, Hiroi clearly teaches polymerization in a solvent to provide for, preferably, a transparent varnish or a dispersed colloidal varnish, and not causing ununiform gelation or turbid precipitation (col.32, lines 46-53). Therefore, in addition to avoiding coating compositions that yield white precipitates, as in Comparative Synthetic Examples 1 and 2, a skilled artisan would monomers in pure forms, i.e., reducing the diester components, to provide for coatings with improved efficiency in inhibiting adhesion to biological substances.
Moreover, the data on record would be limited to compositions based on copolymers, at best, formed from PPM5P (95.6% by mass purity) or PEM5P (87.4% by mass purity (PGPUB-[0128], [0133]) as monomer (1) unit (10-70 mol%), and monomer dimethyl unit (90-30 mol%) that demonstrate improved cell culture promoting property. It is not clear why this limited data would be considered reasonably representative of claim 4, which is open to other monomer (1) species, at 85 mass% or more, based on the total mass of phosphorus containing compounds contained in the mixture, and present at 10-80 mol% of the total monomer mixture, and to monomer (2) of a broad scope. Clearly the data on record is not reasonably commensurate in scope with the claim language.
Conclusion
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 Satya Sastri at (571) 272 1112. The examiner can be reached Monday-Friday, 9AM-5.30PM (EST). If attempts to reach the examiner by telephone
are unsuccessful, the examiner's supervisor, Mr. Robert Jones can be reached at (571)-270-
7733. The fax phone number for the organization where this application or proceeding is
assigned is (571) 273 8300.
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/Satya B Sastri/
Primary Examiner, Art Unit 1762
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