-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 .
This application was transferred to Primary Examiner Alma Pipic in Art Unit 1617.
Applicant’s response dated November 17, 2025 is acknowledged.
Priority
This application is a 371 of PCT/GB2021/051247 filed on 05/21/2021, and claims foreign priority in GB2007701.2 filed on 05/22/2020.
Claim Status
Claims 1-3, 5, 7, 8, 10, and 13-25 are pending. Claims 4, 6, 9, 11, and 12 were canceled. Claims 15, 16, 20, 23, and 24 are withdrawn. Claims 1-3, 5, 7, 8, 10, 13, 14, 17-19, 21, 22, and 25 are examined.
Election/Restriction
Applicant’s election with traverse of Group I (Claims 1-3, 5, 7, 8, 10, 13-19, 21, 22, and 25), drawn to a branched polymer according to Formula I, in the reply filed on November 17, 2025, is acknowledged. The traversal is on the ground that examining both groups can be made without serious search burden.
Applicant’s arguments were fully considered, however they were found unpersuasive. The restriction requirement in the current application is deemed proper because the invention groups lack unity under PCT Rule 13.1 as shown in the restriction requirement. Moreover, Applicant’s arguments regarding search burden are misplaced inasmuch as search burden is not a criterion for restriction under the PCT rules for assessing unity of invention.
Applicant’s election of 4-arm PSS DP50 (example 9.3 on page 46), wherein
PNG
media_image1.png
133
713
media_image1.png
Greyscale
PNG
media_image2.png
123
399
media_image2.png
Greyscale
in the reply dated 11/17/2025 is acknowledged.
The elected species reads on 1-3, 5, 7, 8, 10, 13, 14, 17-19, 21, 22, and 25.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claims 15, 16, 20, 23, and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being withdrawn to a non-elected invention, and non-elected species of the invention, there being no allowable generic or linking claims. Please note that after a final requirement for restriction, the Applicants, in addition to making any response due on the remainder of the action, may petition the Commissioner to review the requirement. Petition may be deferred until after final action on or allowance of claims to the invention elected, but must be filed not later than appeal. A petition will not be considered if reconsideration of the requirement was not requested. (See § 1.181.).
Response to the restriction requirement of July 17, 2025 was timely filed.
Claims 1-3, 5, 7, 8, 10, 13, 14, 17-19, 21, 22, and 25 are examined on the merits.
The elected species was searched and no applicable prior art was found.
The search was extended to all of the species encompassed by claims 13, 14, and 17, and no applicable prior art was found.
The search was extended to the remaining species of branched polymers according to formula I and an office action on those species follows.
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 1-3, 5, 7, 8, 19, 21, 22, and 25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chouifra (Biointerphases, Volume 12, Number 2, 02C418 pages 1-13, Published June 14, 2017).
The claims encompass a branched polymer according to Formula I as described by the claims.
Chouifra teaches poly(sodium styrene sulfonate) (polyNaSS) grafted onto titanium (Ti) surfaces. The grafting process uses a modified dopamine as an anchor molecule to link polyNaSS to the Ti surface. The grafting process combines reversible addition-fragmentation chain transfer polymerization, postpolymerization modification, and thiolene chemistry. The first step in the process is to synthetize architecture controlled polyNaSS with a thiol end group. The second step is the adhesion of the dopamine acrylamide (DA) anchor onto the Ti surfaces. The last step is grafting polyNaSS to the DA-modified Ti surfaces. The modified dopamine anchor group with its bioadhesive properties is essential to link bioactive polymers to the Ti surface. To illustrate the biocompatibility of the grafted Ti-DA-polyNaSS surfaces, their interactions with proteins (albumin and fibronectin) and cells are investigated. Both albumin and fibronectin are readily adsorbed onto Ti-DA-polyNaSS surfaces. The biocompatibility of modified Ti-DA-polyNaSS and control ungrafted Ti surfaces is tested using human bone cells (Saos-2) in cell culture for cell adhesion, proliferation, differentiation, and mineralization (Abstract). Pages 2-3 describe experimental methods used to obtain grafted Ti surface. All control and polyNaSS grafted Ti wafers used for biological assays were sterilized by exposure to a UV germicidal
lamp for 15 min, and then, wafers were flipped over and sterilized for another 15 min. The wafers were then placed individually into wells of tissue culture polystyrene (TCPS) 12-well
plates and treated for 16 h with a sterile solution of serum-free culture medium Dulbecco's Modified Eagle's medium (DMEM)/Hams F12 containing penicillin (100 U ml-1), streptomycin
(l00μgml- 1), and amphotericin B (2.50μgml- 1) at 4 °C (section C on page 3). Scheme 1 teaches preparation of thiolated poly(sodium styrene sulfonate) (page 4), and Table I on page 5 teaches number average molecular weights and degrees of polymerization of four polyNaSS, where degrees of polymerization include 25, 48, and 170. Scheme 2 teaches the grafting process where a titanium surface is functionalized with dopamine acrylamide (DA), followed by grafting with polyNaSS where the thiol end group on polyNaSS reacts with the vinyl group on the DA.
As expected, the smallest molecule (DA) has the highest molecular surface coverage; as measured by QCM-D, the dissipation is relatively low [see Fig. 2(a)] and the surface concentration relatively high in nmol/cm2 or molecules/cm2 (see Table III). The QCM-D results show that a significantly higher number of ~5 kDa polyNaSS-SH macromolecules are grafted onto the Ti-DA surface compared to the other polymers, likely because of fewer steric effects from sulfonate groups along the macromolecular chain when grafting the smaller ~5 kDa polyNaSS-SH. For example, dividing the molecular coverage of DA by the molecular coverage of all polymers shows that the number of DA molecules relative to the number of grafted macromolecules increases as 21 (~5kDa polyNaSS-SH) <53 (~10kDa polyNaSS-SH) <246 (~35 kDa polyNaSS-SH) <457 (~35 kDa polyNaSS). Although there are coverage variations that depend on the molecular weight, the results show that it is possible to graft architecture-controlled polymers of different molecular weights onto the Ti-DA surface (paragraph bridging columns on page 9).
Claim 1 is anticipated by a titanium surface modified with DA and subsequently grafted with PolyNaSS-SH of about 5000 Da molecular weight because:
-the titanium surface modified with DA corresponds to a polyvalent core structure, which is defined in paragraph 0037 of the specification as any moiety having multiple branches capable of covalently bonding to the residues of the polymer chains attached thereto; a titanium wafer surface modified with DA meets this description because each DA molecule reads on a branch,
-a repeating unit of sodium styrene sulfonate corresponds to monomer residue X comprising a sulfonate substituent,
polyNaSS-SH having a molecular weight of about 5000 Da contains about 24 repeating units (each sodium styrene sulfonate unit has a molecular weight of 206 g/mole), which corresponds to claimed variable n and 24 repeating units falls in the claimed range of 5-500,
there is no Y residue therefore q is 0,
the polyNaSS-SH bonds to the titanium surface via the -SH group, therefore the other end group corresponds to the capping group Z, and
according to Table III there are 1.5x1013 molecules of polyNaSS-SH (5000 Da) per centimeter of titanium surface, which reads on claimed variable m and falls in the claimed range of greater than or equal to 3.
Claims 2 and 5 are anticipated because claimed formula II encompasses sodium styrene sulfonate when R1 is aryl substituted with sulfonate, and R2 and R3 are both hydrogen.
Claim 3 is anticipated because the first structure in section b) is a styrene sulfonate anion which encompasses on sodium styrene sulfonate.
Claim 7 is anticipated because all of the claimed ranges encompass 24.
Claim 8 is anticipated because the end group in polyNaSS-SH is the same as the last chemical structure in section b) of the claim.
Claim 19 is anticipated by the composition containing polyNaSS grafted Ti wafers in the sterile solution of sodium-free culture medium Dulbecco’s Modified Eagle’s medium containing penicillin, streptomycin, and amphotericin B.
Claim 21 is anticipated by the composition above because the composition is held in a well of tissue culture polystyrene 12-well plates, which reads on a means for dispensing the composition. The prior art composition meets all of the structural limitations of claimed composition, therefore the prior art composition could have been used as a device for sterilization or viral disinfection and the composition can be dispensed from the wells.
Claim 22 is anticipated by the composition described above because the composition contains the same elements as claimed could have been used as a pharmaceutical composition. Dulbecco’s modified Eagle’s medium is known to contain water, which is a pharmaceutically acceptable excipient.
Claim 25 is anticipated because the composition described above reads on a material.
Claim Rejections – 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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 1-3, 5, 7, 8, 10, 18, 19, 21, 22, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Xu (US 2016/0340460 A1 Published November 24, 2016 – of record in IDS 11/21/2022).
The claims encompass a branched polymer according to Formula I.
The teachings of Xu are related to sulfonated polyphosphazene copolymers (Abstract).
PNG
media_image3.png
418
455
media_image3.png
Greyscale
(paragraph 0012), wherein Rl is -OCH3 or -F; R2 is Na or H; n is the number of phosphazene residue units, i.e. the length of a polyphosphazene chain; x is the number of styrene residue units, and ranges from 0 to 100; y is the number of p-( 4-sulfonato butoxy) styrene residue units, and ranges from 0 to 100; 111 is the number of combination units of styrene residues and p-( 4-sulfonato butoxy) styrene residues, and ranges from 0 to 100; r indicates that the copolymer of styrene residue and p-(4-sulfonato butoxy) styrene residue is a random copolymer (paragraph 0013). An example of a polymer includes poly( 4-fluoro phenoxy)( 4-methyl phenoxy)phosphazenegraft-poly{(styrene )x-co-[ 4-( 4-sulfonato butoxy)styrene]y} (F-PSx-PSBOSy) (paragraph 0019) and more specifically F-PSBOS26 and M-PSBOS40 (paragraph 0026). Example 2 teaches a method of making poly[(4-fluoro phenoxy)( 4-methyl phenoxy)phosphazene-graft-poly{(styrene )x -co-[4-(4-sulfonato butoxy)styrene]y} (F-PSx-PSBOSy) and provides Table 1 with molecular weights and graft lengths (paragraphs 0042 and 0043).
Xu does not state the number of repeating units without the graft and the number of repeating units with the graft in F-PSBOS26. Table 1 provides molecular weights of craft copolymers. It would have been prima facie obvious to a person skilled in the art to have formed F-PSBOS26 having a number average molecular weight of 1.13x105 and weight average molecular weight of 1.94x105 with a reasonable expectation of success because Table 1 teaches said combination of molecular weights for a graft copolymer F-PAS26. Xu teaches that the units without the graft are present in the amount of (0.5-0.9)n and the units with the graft are present in the amount of (0.1-0.5)n where n is the length of the polymer chain. In poly[(4-fluoro phenoxy)( 4-methyl phenoxy)phosphazene-graft-[4-(4-sulfonatobutoxy)styrene]26} (F-PSBOS26 ), the molecular weight of the residue without the graft is 282 g/mole and the molecular weight of the residue with the graft is 7536 g/mole. The molecular weight of the grafted residue was calculated based on the sodium salt of the sulfonate. It would have been obvious to vary the number of repeating units with the graft and without the graft in order to form a copolymer that meets the parameters set forth by Xu. A graft copolymer having a number average molecular weight of 113,000 Da would contain at most 14 repeating units of grafted residue because 15 repeating units is equal to the entire polymer weight. Therefore, the remaining molecular weigh would be repeating units without the graft. Fourteen units is equal to 105,504 Da (14*7536 Da). The difference between the total weight of the copolymer and the total weight of the 14 grafted units is 7496 Da (113,000-105,504), therefore there would have been 26 residues without a graft (7496/282). A graft copolymer having 14 grafted and 26 ungrafted residues has a total of 40 residues and the ratio of the grafted to ungrafted is 0.35:0.65. A graft copolymer having 12 grafted (90,432 Da) and 80 ungrafted (22,560 Da) repeating units has a ratio of grafted to ungrafted of 0.13:0.87. The values fall in the ranges of ratios of grafted to ungrafted residues taught by Xu. The above calculation was done as an example of how the number of repeating units without the graft and with the graft would be calculated.
The claimed branched polymer is obvious over Xu’s graft copolymer having 12-14 grafts of poly-[4-(4-sulfonatobutoxy)styrene]26 because
-the polymer backbone corresponds to the polyvalent core structure,
-[4-(4-sulfonatobutoxy)styrene] corresponds to the X residue having a sulfonate substituent,
-Y is absent,
-any moiety that terminates that poly-[4-(4-sulfonatobutoxy)styrene]26 corresponds to Z, a person skilled in the art would have understood that once the polymerization reaction is complete the formed polymer is complete and has an end group,
-the number of grafts corresponds to m, which is obvious because it encompasses 12-14,
-the number of repeating [4-(4-sulfonatobutoxy)styrene] residues corresponds to n, which is obvious because it encompasses 26, and
-q is 0.
Claims 2, 3, and 5 are obvious over 4-(4-sulfonatobutoxy)styrene because it is encompassed by formula II when R3 and R2 are both hydrogen atoms, and R1 is aryl (phenyl in claim 3) substituted with sulfonate and C4alkoxy.
Claim 7 is obvious because the claimed ranges encompass 26, which is the number of 4-(4-sulfonatobutoxy)styrene repeating units.
Regarding claim 8, the polymer of 4-(4-sulfonatobutoxy)styrene has a hydrogen atom on the last repeating unit, which reads on a capping group.
Regarding claim 10, the claim is obvious because Xu’s polymer does not contain a monomer Y, which meets the limitation where q is 0. The range of m is obvious because the range of 3 to 12 encompasses 12. Xu’s graft copolymer as shown above contains an embodiment having 12 repeating units grafted with 4-(4-sulfonatobutoxy)styrene26.
Regarding claim 18, it would have been obvious to have varied the number of residues of 4-(4-sulfonatobutoxy)styrene within the graft up to 100 with a reasonable expectation of success because Xu teaches that the number of said units ranges from 0 to 100. A residue grafted with 91 4-(4-sulfonatobutoxy)styrene would have a molecular weight of 25,671 Da ((279*91)+282). A grafted copolymer of molecular weight 113,000 Da having 4 grafted residues would have 36 residues without grafts. Four grafted residues would have a molecular weight of 102,684 Da. The difference between the total weight of the graft copolymer and the total weight of the grafted units corresponds to the total molecular weight of the residues without grafts (113,000-102,684 = 10,316). Dividing 10,316 by molecular weight of a residue without a graft (282 Da) provides the number of repeating units without a graft (10,316/282), which is 36. The ratio of grafted units to units without a graft is 0.1:0.9 which falls in the range required by Xu. Xu requires (0.5-0.9)n units that are not grafted and (0.1-0.5)n grafted units. The claimed range of n is obvious because it encompasses 91. Xu’s graft does not contain a monomer Y therefore q is 0. Xu’s graft copolymer contains four grafted repeating units which meets the limitation m is 4. It is noted that Xu teaches a genus of graft copolymers where the numbers of repeating units in the copolymer and the graft vary over a range of values, and it would have been obvious to have formed Xu’s graft copolymer by varying those ranges and Xu’s genus of graft copolymers would have overlapped with the claimed genus of copolymers.
Regarding claim 19, Xu’s method of making the graft copolymer results in a composition comprising said graft copolymer, which meets the claimed limitation of a composition.
Regarding claims 21 and 25, it would have been obvious to have formed a membrane from the graft copolymer as described above because Xu teaches forming a membrane through film forming by solution casting method (paragraph 0021), a membrane reads on a device and because it has the same chemical composition as claimed, it could have been used as a device for sterilization or viral disinfection, absent evidence to the contrary. The membrane is made through solution casting, and the skilled artisan would have understood that a container was used to form the film and the container reads on a means for dispensing the composition. The formed film could have been dispensed from the container after formation. A membrane formed form the graft copolymers reads on a material comprising the graft copolymer.
Regarding claims 22 and 25, it would have been obvious to have added water to the reaction mixture from which the grafted copolymer was formed because Xu teaches adding water to the reaction mixture in order to precipitate the product (paragraph 0037). This embodiment meets the claimed limitations because water is a pharmaceutically acceptable excipient and the composition reads on a pharmaceutical composition because it contains the same components as claimed. A composition comprising the graft copolymer and water reads on a material comprising the graft copolymer.
Conclusion
Claims 1-3, 5, 7, 8, 10, 18, 19, 21, 22, and 25 are rejected. Claims 13, 14, and 17 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alma - Pipic whose telephone number is (571)270-7459. The examiner can normally be reached M-F 9:00am-5:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached on 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALMA PIPIC/Primary Examiner, Art Unit 1617