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 .
The amendment filed 6/19/2025 has been entered. Claims 1-24, 26-29, 40-41, and 43-44 have been canceled. New claims 45-46 have been added. Claims 25, 30-39, 42, and 45-46 are pending in the application. New claims 45-46, similar to cancelled claims 40-41 that were not elected without traverse in the response filed 10/31/2024 (although also cancelled), have been withdrawn from consideration as being directed to non-elected inventions (in light of Applicant’s election without traverse dated 10/31/2024 and/or election by original presentation due to the lack of unity of invention for reasons similar to those recited in the Office Action dated 9/10/2024 and as evidenced by Hou), and contrary to Applicant’s statements in the response filed 10/31/2024 (see paragraph bridging pages 1-2), prior art applied by the Office in rejecting elected claims is not barred from being similarly applied to unelected claims should Applicant pursue those claims in a divisional application.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 102
Claims 25, 30-39, and 42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hou (Precisely Structured Nitric-Oxide-Releasing Copolymer Brush Defeats Broad-Spectrum Catheter-Associated Biofilm Infections In Vivo, printed prior to the effective filing date of 12/17/2020, and including additional authors other than the two joint inventors of the present application) for the reasons recited in the prior office action and restated below, wherein it is noted that because the authors of the Hou article are not all within the inventive entity of the present application, and there is no evidence or explanation with respect to the involvement of the additional authors, the publication is not considered inventor originated and thus an exception under AIA 35 U.S.C. 102(b)(1)(A) does not apply (see MPEP §§ 2153.01 and 2155.01).
As discussed in the prior office action, Hou discloses a composite material comprising a polyurethane substrate (as in instant claims 31-32) coated with a poly(hydroxyethyl methacrylate)-block-poly(sulfobetaine methacrylate) copolymer (hereinafter “P(HEMA)-b-P(SMBA)”) brush (as in instant claim 25), wherein the P(HEMA) block, as the claimed first block comprising a hydrophobic polymer (as in instant claims 25, 33-36, and 39), is covalently grafted to the surface of the polyurethane substrate and after polymerization of the P(SBMA) block (as the claimed second block of a hydrophilic polymer extending from the first block to form an outer surface of the block copolymer brush as in instant claims 25 and 37-39), the P(HEMA) block is conjugated to a nitric oxide (NO) source (as in instant claim 25), typically S-nitrosothiols (RSNO), by reacting with the RSNO-donor, specifically 3-nitrosothiol-3-methylbutan-chloride (NTMB-Cl, e.g. a tertiary S-nitrosothiol as in amended claim 25) to produce P(HEMA-NO)-b-P(SMBA), a nitric acid (NO)-emitting block copolymer brush coating covalently bonded to the polyurethane substrate, with examples having a thickness of about 10 µm (as in instant claim 30; Entire document, particularly pp. 2031-2034). Hence, Hou anticipates instant claims 25, 30-39 and 42.
Claim Rejections - 35 USC § 103
Claims 25, 30-39, and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Lawin (WO2018/213627A1, also printed as US2021/0002493A1, please refer to the US PG Pub document for the below cited sections) in view of Hou or Stamler (US2001/0020083A1) or Rong (Nitric Oxide-Releasing Polymeric Materials for Antimicrobial Applications: A Review), for generally the reasons recited in the prior office action and restated below with respect to the amended claims.
As discussed in the prior office action, Lawin teaches zwitterionic monomers such as sulfobetaines including (meth)acryl esters thereof like N-(3-Sulfopropyl)N-methacryloyloxy-ethyl-N,N-dimethyl ammonium betaine (Paragraphs 0163-0174, hence clearly suggesting sulfobetaine methacrylate); non-zwitterionic monomers such as non-zwitterionic (meth)acryl ester monomers that can include a functional group such as a hydroxyl group (Paragraphs 0175-0186, hence, clearly suggesting hydroxyethyl methacrylate); and polyzwitterionic polymers formed therefrom (Abstract), such as by reversible addition-fragmentation chain transfer (RAFT) polymerization under various conditions in order to provide a desired polymer architecture such as brush polymers and comb polymers (Paragraphs 0196-0197), wherein the polymers may include block copolymers of one or more zwitterionic monomers and one or more non-zwitterionic monomers providing a (co)polymer of the general structure as shown in Formula 12 (copied below) and described in Paragraphs 0209-0224; as well as surfaces and/or substrates that are functionalized or modified by the (co)polymers as surface reagents to impart desired surface properties, such as hydrophilicity, excellent resistance to biofouling, and anti-fouling properties of any type (Abstract, Paragraphs 0004-0007, 0145, 0270-0272, 0274-0278, 0281, 0296, 0302-0304, 0307, and 0320) by covalent attachment of the zwitterionic (co)polymers at one pendant position to form brush configurations as shown in Figs. 2A-2B (copied below), or at two or more positions to form a network configuration as shown in Figs. 2C-2D (Paragraphs 0158, 0197, 0298-0299, 0335).
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Lawin teaches that the (co)polymer may be attached to the surface by either terminal group, T1 or T2 (Paragraphs 0212-0214 and 0332-0335) and that the order of monomer introduction into the polymerization system can be controlled to provide the desired polymer structure, wherein for example, the zwitterionic monomer(s) can be introduced first and/or last to be located near one terminal, e.g. T2 as in the above formula, or both termini of the polymer, with the non-zwitterionic monomer(s) introduced after or between introduction of the zwitterionic monomer(s) and/or at the end of polymerization of the zwitterionic monomer(s) to be located near the other terminal, e.g. T1 in the above formula, or vice versa (Paragraph 0211); and given that Lawin clearly teaches that the copolymer may be a block copolymer of one zwitterionic monomer and one non-zwitterionic monomer with only one terminal end attached to the substrate in a brush configuration as noted above, Lawin provides a clear teaching and/or suggestion of a diblock copolymer brush comprising a first block of a zwitterionic polymer (e.g. a cationic polymer) that is covalently bonded to a substrate surface and a second block of a zwitterionic or non-zwitterionic polymer (e.g. hydrophilic polymer particularly given the teaching of providing a hydrophilic surface) that extends from the first block to form an outer surface of the diblock copolymer brush; or alternatively, a diblock copolymer brush comprising a first block of a non-zwitterionic polymer (e.g. a hydrophobic polymer given the (meth)acrylate monomers taught by Lawin) that is covalently bonded to a substrate surface and a second block of a zwitterionic polymer (e.g. a hydrophilic polymer) that extends from the first block to form an outer surface of the diblock copolymer brush (e.g. similar to the block copolymer brush structure(s) of instant claim 25) given that it is prima facie obviousness to choose from a finite number of identified, predictable solutions, with a reasonable expectation of success. Lawin also teaches that surface reagents can be utilized to attach or conjugate secondary compound(s) which can also be utilized to provide other properties or functionalities to the modified surface such as conjugated drugs for drug delivery/release and conjugated bioreactive moieties (Entire document, particularly as noted above, Figs. 1-2, Paragraphs 0269, 0279, 0306, and 0310). Hence, with respect to the claimed invention, Lawin provides a clear teaching and/or suggestion of a composite material comprising a substrate coated with a block copolymer brush, where the block copolymer brush comprises a first block of a hydrophobic polymer and a second block of a hydrophilic polymer as instantly claimed, particularly polymers of monomers as recited in instant claims 33-39, and although Lawin teaches that drug compounds or bioreactive compounds can be conjugated with the zwitterionic (co)polymers, Lawin does not specifically teach conjugating a nitric oxide source, particularly a tertiary S-nitrosothiol, to the hydrophobic polymer of the first block as recited in amended claim 25.
However, it is noted that a nitric oxide source is a known therapeutic and/or antibacterial agent in the art, wherein each of Hou (discussed in detail above), Stamler (Entire document, particularly Abstract, Paragraphs 0002-0020, 0025-0026, and 0065), and Rong (Entire document, particularly Abstract, Section 1. Introduction, Section 4. NO Donors for Antibacterial Application, and Section 5. NO Releasing Polymeric Materials for Antibacterial Applications) teaches conjugating a nitric oxide source, particularly a tertiary S-nitrosothiol (as in amended claim 25) to synthetic (co)polymeric materials, including block, brush and/or graft copolymers (Hou: Abstract; Stamler: Paragraph 0025; Rong: pp. 2 and 8) as in Lawin, particularly for polymeric coatings of (bio)medical devices (Hou: Abstract; Stamler: Abstract; Rong: Abstract, Introduction) to provide antibacterial and/or anti-biofilm properties as in Lawin; and given that Lawin is in the same field of endeavor as Hou, Stamler, and/or Rong, e.g. the medical field, particularly medical devices including implantable medical devices, and also concerned with providing a surface resistant to biofouling, biofilm formation, and bacterial growth, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to conjugate a nitric acid source, particularly a tertiary S-nitrosothiol as in Hou, Stamler, or Rong, to either or both the zwitterionic polymer block(s) and/or the non-zwitterionic polymer block(s) of the copolymers taught by Lawin, e.g. as a bioreactive compound, given that it is prima facie obviousness to combine prior art elements according to known methods to yield predictable results (Lawin: Paragraphs 0001-0006, 0208, 0320, 0330, and Examples). Hence, absent any clear showing of unexpected results, the Examiner maintains her position that the claimed invention as recited in instant claims 25, 33-39, and 42 would have been obvious over the teachings of Lawin in view of Hou or Stamler or Rong for the reasons discussed above.
With respect to instant claim 30, although Lawin does not teach a thickness of the resulting polymer layer attached to the surface by functionalization or modification with the zwitterionic copolymer(s), one having ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to determine the optimum thickness to provide the desired properties taught by Lawin for a particular end use; and hence, absent any clear showing of criticality and/or unexpected results with respect to the claimed thickness range, the claimed invention as recited in instant claim 30 would have been obvious over the teachings of Lawin in view of Hou or Stamler or Rong, particularly given that a thickness within the claimed range is typical in the art as evidenced by Hou which teaches a coating thickness of about 10 µm as discussed in detail above.
With respect to instant claims 31-32, Lawin teaches that surfaces to be modified or functionalized with the zwitterionic (co)polymers include polymeric materials such as polyurethanes, particularly polyester polyurethane and polyether polyurethane (Paragraphs 0309-0327 and 0484); and hence the claimed invention as recited in instant claims 31-32 would have been obvious over the teachings of Lawin in view of Hou or Stamler or Rong given that it is prima facie obviousness to choose from a finite number of identified, predictable solutions, with a reasonable expectation of success.
Response to Arguments
Applicant's arguments filed 6/19/2025 have been fully considered but they are not persuasive with respect to the anticipation rejection over Hou, nor the obviousness rejection over Lawin in view of Hou, Stamler, or Rong. In terms of the anticipation rejection over Hou, the Applicant argues that the Hou reference is not prior art because “Hou was published less than one (1) year before the effective filing date of the pending application and that the inventors of the present application are also the authors of the cited Hou reference” and “[t]herefore, Hou is not prior art as set forth in 35 U.S.C. 102(b)(1)” (see Section VII of the response). However, the Examiner respectfully disagrees given that as noted above, the authors of the Hou article are not all within the inventive entity of the present application, and there is no evidence or explanation with respect to the involvement of the additional authors, and thus, the publication is not considered inventor originated and an exception under AIA 35 U.S.C. 102(b)(1)(A) does not apply (see MPEP §§ 2153.01 and 2155.01). More specifically, the present application only lists two joint co-inventors, Zheng Hou and Bee Eng Mary Chan, however, the Hou non-patent literature document lists 14 co-authors: Zheng Hou, Yang Wu, Chen Xu, Sheethal Reghu, Zifang Shang, Jingjie Chen, Dicky Pranantyo, Kalisvar Marimuth, Partha Pratim De, Oon Tek Ng, Kevin Pethe, En-Tang Kang, Peng Li, and Mary B. Chan-Park (same as co-inventor Bee Eng Mary Chan), only two of which (in bold and underlined) are listed as the two joint co-inventors of the present application, however, there is no evidence or explanation for the involvement of the other 12 co-authors of the non-patent document, namely, Yang Wu, Chen Xu, Sheethal Reghu, Zifang Shang, Jingjie Chen, Dicky Pranantyo, Kalisvar Marimuth, Partha Pratim De, Oon Tek Ng, Kevin Pethe, En-Tang Kang, and Peng Li (See MPEP § 2153.01 and particularly § 2155.01, Example 1). Hence, Applicant’s arguments over Hou are not persuasive.
In terms of the obviousness rejection over Lawin in view of Hou or Stamler or Rong, the Applicant first argues that the Examiner allegedly fails to meet the standard required in order to establish a prima facie case of obviousness, arguing that “[a]s explained in Example 6 of the present application, the composite material of amended Claim 25 demonstrates no toxicity toward all tested mammalian cell lines” and thus “displays good biocompatibility” (see pages 11-12). The Applicant also argues that the “present application also shows that the composite material of amended Claim 25 is chemically stable with no leaching of the NO-donor detected (see Example 4), has significant short-term and long-term antibacterial and antibiofilm effects against pathogens (see Example 5), reduced protein fouling (see Example 9), and does not induce inflammation (see Example 10),” further arguing that “the above-mentioned features, as well as the associated advantages, are not taught or suggested by the cited documents” (see first to paragraphs of page 13). However, the Examiner notes that the “above-mentioned features” upon which Applicant relies are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). It is also noted that with respect to the “above-mentioned features” as argued by the Applicant, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985), and given that the Applicant provide no evidence that such features or properties represent “unexpected” results, Applicant’s arguments with respect to said features are not persuasive.
On pages 13-14 of the response, the Applicant argues that allegedly “one having ordinary skill in the art would not modify the material of Lawin and arrive at the present invention because there is [allegedly] no motivation to do so,” arguing that “Lawin discloses that the polymer may include block copolymers of one or more zwitterionic monomers and one or more non-zwitterionic monomers providing a copolymer of the general structure as shown in Formula 12 (emphasis in original), but that none of the Examples in Lawin actually discloses the use of block copolymers. The Applicant then argues that “there [allegedly] is no teaching or suggestion that would (not simply could) have prompted one having ordinary skill in the art to modify the material of Lawin to arrive at the claimed composite material with a first block of a hydrophobic polymer conjugated to a tertiary S-nitrosothiol nitric oxide source and a second block of a hydrophilic polymer extending from the first block to form an outer surface of the block copolymer brush” (emphasis in original). However, the Examiner respectfully disagrees and again notes that Lawin clearly teaches that the copolymer may be a block copolymer of one zwitterionic monomer and one non-zwitterionic monomer with only one terminal end attached to the substrate in a brush configuration as discussed in detail above, and although the Lawin examples noted by the Applicant utilize random copolymers, Lawin clearly states that the examples “should not be construed to unduly limit” the disclosure (Paragraph 0508), and thus the reference as a whole has been utilized by the Examiner in assessing the patentability of the instant claims. The Applicant also argues that “even if the skilled person were to modify the material of Lawin, the skilled person [allegedly] would not have arrived at the present invention with the expectation of achieving the [alleged] superior performance as demonstrated in Examples of the present application, particularly when compared to other copolymer arrangements (e.g. cross-linked arrangement (#8), random arrangement (#9)),” noting again that “none of the Examples in Lawin actually disclose the use of block copolymers” and “[i]n other words, these superior performance results are [allegedly] unexpected” (see last paragraph on page 14). However, the Examiner respectfully disagrees and first notes that the data and results relied upon by the Applicant, as summarized in Table 1 of the specification, are not commensurate in scope with the claimed invention, e.g. all of the compared examples mentioned by the Applicant utilize HEMA and SBMA for the block copolymer, while the instant claims (except instant claim 39) are much broader with respect to the blocks of the block copolymer, and all of the examples utilize an ozone-treated polyurethane substrate/catheter, such that one skilled in the art could not reasonably extend the probative value thereof to any hydrophobic polymer block in combination with any hydrophilic polymer block, and any substrate. Further, the results do not appear to provide any clear showing of “unexpected” results over the teachings of the cited prior art given that the compared examples do not represent the teachings of Lawin and one skilled in the art would clearly recognize that when providing a coating on the surface of a catheter or similar device, hydrophilicity is important such that one skilled in the art would be motivated to ensure that sufficient functional or hydrophilic groups are on the outer surface of the coating such that Applicant’s arguments with respect to alleged “superior performance” are not persuasive, especially given that Lawin specifically teaches that the invention can be utilized for surface functionalization and/or modification including providing surface properties such as hydrophilicity and lubricity, and more particularly, with respect to medical devices, reciting in the background that “medical devices used in vascular interventional procedures employ hydrophilic coatings to reduce the procedure time and impart a high degree of lubricity which lowers the frictional force during insertion and manipulation of the device through the circulatory system, thus avoiding puncture damage and abrasion between the medical device surface and vessel walls” and that “[m]edical devices that could benefit from having low fouling, low coefficient of friction, protein adhesion resistant, antithrombogenic and hemocompatible properties include but are not limited to seals including plunger seals, implantable devices, implantable and non-implantable sensors and drug delivery devices, tissue scaffolds, non-invasive and minimally invasive apparatus, and wound dressings” (and as also evidenced by Pinchuk, US2002/0107330A1, referenced below, Entire document).
The Applicant further argues that with respect to the other cited documents, i.e. the secondary references utilized in the rejection, Hou is allegedly not prior art for the same reasons as discussed above and addressed by the Examiner with respect to the anticipation rejection, and hence Applicant’s arguments over Hou are not persuasive; while Stamler and Rong do not cure the alleged deficiency of Lawin with respect to the claimed specific arrangement or block copolymer structure, and given the Examiner’s response above and incorporated herein by reference with respect to the teachings of Lawin, Applicant’s arguments are pages 15-16 of the response are not persuasive and the Examiner maintains her position that the claimed invention would have been obvious over the combined teachings of the cited prior art as discussed above.
Any objection or rejection from the prior office action not restated above has been withdrawn by the Examiner in light of Applicant’s claim amendments and arguments filed 6/19/2025.
Citation of pertinent prior art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Pinchuk (US2002/0107330A1) discloses a composition for drug delivery and medical devices formed from the composition; wherein the composition comprises a therapeutic agent and a biocompatible block copolymer comprising one or more elastomeric blocks, preferably polyolefin blocks; and one or more thermoplastic blocks, preferably vinyl aromatic or methacrylate blocks wherein the methacrylate block may be formed from hydroxyethyl methacrylate monomers, and the therapeutic agent can be covalently bonded, hydrogen bonded, or electrostatically bound to the copolymer, with specific examples including nitric oxide releasing functional groups such as S-nitroso-thiols.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MONIQUE R JACKSON whose telephone number is (571)272-1508. The examiner can normally be reached Mondays-Thursdays from 10:00AM-5:00PM.
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/MONIQUE R JACKSON/Primary Examiner, Art Unit 1787