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 .
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.
Response to Amendment
This action is a response to the amendment filed April 13, 2026. Claims 2-4, 7-8, 10-11, and 17-18 are cancelled. Applicants cancellation of claims 10 has rendered the corresponding rejections previously set forth in the Non-Final Office Action mailed January 15, 2026 moot.
Applicant’s arguments filed April 13, 2026 were fully considered but they were not persuasive. Maintained rejections and response to arguments are addressed below.
Claims 1, 5-6, 9, 12-16, and 19 are pending in this application.
Priority
This application is the U.S. National Phase Application under 35 U.S.C. § 371 of International Application No. PCT/GB2019/053633, filed December 19, 2019, designating the U.S. and published in English as WO 2020/144454 Al on July 16, 2020. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been received.
Claim Interpretation
Claim 1 recites inter alia, “wherein the method further comprises blocking the oxidized polypropylene surface comprising the oligonucleotide immobilized thereto with a blocking agent, and wherein the blocking agent comprises alkali or alkaline earth metal borohydrides.”. A method of treating the oxidized surface comprising immobilized oligonucleotide with sodium cyanoborohydride would anticipate the present claims, whether or not the borohydride reagent is referred to as “a blocking agent”.
Maintained 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, 5-6, 9, and 12-16 are rejected under 35 U.S.C. 103 as being unpatentable over Gubala et al (Colloids and Surfaces B: Biointerfaces, 2010, IDS filed October 22, 2021) in view of Kumar (Bioconjugate Chemistry, 2003, IDS filed October 22, 2023), Shahidzadeh-Ahmadi (Colloids and Surfaces, 1996, cited in previous action) and Fan (WO 2015/031691, cited in previous action) as evidenced by ThermoFisher Scientific (Cy5 Dye, 2024, cited in previous action).
Regarding claims 1, 5-6, 9, and 12-16: Gubala teaches a method of immobilizing and oligonucleotide on a plastic surface that is a cyclo-olefin polymer (COP, abstract). Gubala teaches the method comprises oxidizing plain COP slides (i.e. surface of a slide) with oxygen plasma, incubation with Cy5 modified ssDNA (5’-Cy5, 3’-NH2), in which the 3’-amino terminal reacts with aldehydes produced on the oxidized surface producing a Schiff base that is subsequently reduced with treatment of NaBH3CN for 1 hour (pg. 545, figure 2, pg. 546, col. 1, last para.). According to ThermoFisher Scientific, Cy5 dye is a fluorescent cyanine dye (pg. 1, para. 1). Gubala teaches a method wherein the contacting step (i.e. incubating polymer surface with oligonucleotide) occurs in the presence of MES buffer for 2 hours (pgs. 546-547, bridging para.). Following incubation the well was then treated with a solution of NaBH3CN (metal borohydride, pg. 547, col. 1, para. 1). Gubala teaches exemplary functional modifications of a plastic surface for attachment of DNA:
PNG
media_image1.png
365
831
media_image1.png
Greyscale
(pg. 545, scheme 1). As shown in the above scheme, the resulting imine is reduced to an imine with a reducing agent (sodium cyanoborohydride). Gubala teaches reduction of the imine to amines with reducing agents such as borohydrides if good practice due to instability of the imine (pg. 546, col. 1, para. 2). Based upon page 8 of the instant specification the blocking/reducing agents are interpreted to be referring to the same active step of the method:
PNG
media_image2.png
106
581
media_image2.png
Greyscale
(lines 14-17). Wherein the borohydride reagent is added to reduce the imine bond, it necessarily acts as a blocking agent, absent evidence to the contrary. Gubala teaches that oxidized slides for spotting were used immediately and longer exposure to air was avoided, suggesting the incubation with oligonucleotides was performed under ambient conditions (pg. 546, col. 1, last para.). Gubala does not teach special conditions that would lead one away from performing under ambient temperature and humidity as recited by instant claim 16.
Gubala does not teach wherein the plastic material is polypropylene instead of COP.
However, Kumar teaches a method of immobilizing amino terminal oligonucleotides on an activated polypropylene surface (abstract). Kumar teaches functional groups can be generated on polypropylene surfaces via chemical methods or oxidation of the backbone of the polymer, or photochemical activation (pg. 510, col. 1, para. 2). Fan teaches microwell arrays can be fabricated from a number of suitable materials such as polypropylene or cyclic olefin polymers (abstract, pg. 41, para. 00185). The support can be utilized for the immobilization of biological particles and macromolecules, such as DNA and RNA, in hybridization assays (pg. 29, para. 00146, pg. 36, paras. 00170-00171). Typically hydrophobic materials can be treated by oxygen plasma treatment (pg. 41, para. 00185). Compatible solid support functional groups include aldehydes (pgs. 2-3, para. 0004). Fan establishes polypropylene and cyclic olefin polymers as substitutable surfaces (pg. 41, para. 00185). Shahidzadeh-Ahmadi establishes oxygen plasma treated polypropylene surfaces result in formation of various functional groups including, hydroxyl, carbonyl, and carboxylate groups at the surface (abstract, pg. 288, col. 1, para. 1, col. 2, paras. 2-3).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to modify the method of Gubala by substituting the COP surface with a polypropylene material for the immobilization of amin-terminated oligonucleotides as taught by Kumar, Shahidzadeh, and Fan. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success given that polypropylene is known in the art as a oxidizable surface for the immobilization of oligonucleotides, is known to form carbonyl groups following oxygen plasma oxidation, and is generally taught as an alternative to cyclic olefin polymers, it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06 (II)).
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Gubala et al (Colloids and Surfaces B: Biointerfaces, 2010, IDS filed October 22, 2021), Kumar (Bioconjugate Chemistry, 2003, IDS filed October 22, 2023), Shahidzadeh-Ahmadi (Colloids and Surfaces, 1996, cited in previous action), Fan (WO 2015/031691, cited in previous action), and ThermoFisher Scientific (Cy5 Dye, 2024, cited in previous action) as applied to claims 1, 5-6, 9, and 12-16 above in view of Billman et al (J. Org. Chem, 1957, cited in previous action).
Regarding claims 19: As discussed above, the prior art render obvious the method of claims 1 and 10. They teach a method of reducing the Schiff base with sodium cyanoborohydride.
They do not teach wherein the reduction is carried out with sodium borohydride.
However, Billman teaches sodium borohydride is an effective reagent for the reduction of Schiff bases (abstract). Whereas Gubala suggests that reduction of Schiff bases with borohydride containing reagents is known in the art, and sodium borohydride is an established reducing agent for such a reduction, it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06 (II)).
Taken together it would have been prima facie obvious to a person of ordinary skill to further modify the method by substituting sodium cyanoborohydride with sodium borohydride as taught by Billman. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success, given that both reagents are known the art to successfully reduce Schiff bases.
Maintained Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 5-6, 9, 12-16, and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 17/421,108 (US 2022/0154260) in view of Gubala et al (Colloids and Surfaces B: Biointerfaces, 2010, IDS filed October 22, 2021) as evidenced by ThermoFisher Scientific (Cy5 Dye, 2024, cited in previous action). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 1, 5-6, 9, 12, 19: The copending claims teach a method of immobilizing an oligonucleotide on a polypropylene surface, the method comprising oxidizing at least a portion of the polypropylene surface and contacting an amine terminating oligonucleotide with the oxidized surface to immobilize the oligonucleotide to the surface via the formation of amide bonds (claim 1). The oxidizing step is carried out with oxygen plasma (claim 3). The oligonucleotide is ssDNA (claim 4). The ssDNA can be a fluorescent labelled ssDNA (claims 5 and 12). The incubation of oligonucleotide and oxidized surface is performed in the presence of a buffer, such as MES (claims 7-8). The surface is the surface of a plug or a cassette for a hybridization array or surface of a slide (claim 9).
The copending claims differ from the instant claims in that the copending claims involve the steps of reacting the amine terminated oligonucleotide with the oxidized polypropylene surface in the presence of a carbodiimide coupling agent to immobilize the oligonucleotide, followed by blocking the oligonucleotide surface with sodium borohydride (claims 1 and 10-11). The copending claims do not explicitly teach a method wherein the amine reacts with the oxidized surface to form an imine which is subsequently reduced with sodium borohydride.
However, according to the instant specification, oxygen plasma oxidation results in the formation of aldehydes on the polypropylene surface (pg. 5, lines 9-18). Gubala discloses that COOH groups react with amines in the presence of coupling agents, such as carbodiimides, while aldehydes react spontaneously with amines (pg. 545, col. 1, para. 2). Gubala discloses reduction of the imine to amines with reducing agents such as borohydrides if good practice due to instability of the imine (pg. 546, col. 1, para. 2). Given that the surface of polypropylene in the copending application is oxidized with oxygen plasma, reacted with a terminal amine, and treated with sodium borohydride, it would have been prima facie obvious to modify the method of the copending application by omitting the use of carbodiimide to allow the terminal amines to react the surface aldehydes produced by oxidation. One of ordinary skill in the art would have the motivation to do so as carbodiimide reactions or imine formation followed by reduction are known as suitable alternatives in the art.
Regarding claims 13-14: As discussed above, the copending application renders obvious the methods of claims 1 and 15.
The copending application did not teach wherein the fluorescent labelled DNA comprises a fluorescent cyanine or ruthenium dye, wherein the terminal amine group is a 5’ or 3’ amine group. The copending claims do not specify wherein the incubation occurs for a period of 5 minutes to 14 days.
However Gubala teaches the reaction of a fluorescent Cy5 ssDNA with a 3’ terminal amine and the oxidized surface (via plasma activation) of a plastic material:
PNG
media_image3.png
139
183
media_image3.png
Greyscale
(pg. 545, fig. 2). According to ThermoFisher Scientific, Cy5 dye is a fluorescent cyanine dye (pg. 1, para. 1). Gubala teaches a method wherein the contacting step (i.e. incubating polymer surface with oligonucleotide) occurs in the presence of MES buffer for 2 hours (pgs. 546-547, bridging para.). Following incubation the well was then treated with a solution of NaBH3CN (metal borohydride, pg. 547, col. 1, para. 1). It would have been prima facie obvious to modify the method of the copending application such that the fluorescent ssDNA is a Cy5 labeled ssDNA with 3’ terminal amine that is incubated for 2 hours as taught by Gubala and Fan. One of ordinary skill in the art would have the motivation to do so as utilization of detectable labels during oligonucleotide immobilization for hybridization assays is a routine practice in the art. A person would be motivated to apply the incubation conditions of Gubala as this time was demonstrated to be successful in the art to facilitate the reaction.
Regarding claims 16: The copending claims do not specify wherein the incubating is performed under ambient temperature and humidity conditions as claimed.
Gubala teaches that oxidized slides for spotting were used immediately and longer exposure to air was avoided, suggesting the incubation with oligonucleotides was performed under ambient conditions (pg. 546, col. 1, last para.). Gubala does not teach special conditions that would lead one away from performing under ambient temperature and humidity as recited by instant claim 16. It would have been prima facie obvious to utilize ambient temperature and humidity conditions as non-ambient conditions are not taught by Gubala and a person of ordinary skill would understand that these are the conditions utilized, absent evidence to the contrary.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant’s arguments filed April 13, 2026 have been fully considered but they are not persuasive.
On page 5 of Applicant’s response, Applicant argues that plasma treatment of COP results in the formation of functional groups initiated by cyclopentane ring opening, however polypropylene does not contain any ring structures and thus a person of ordinary skill in the art would not consider polypropylene to be a suitable alternative to COP as a substrate for surface oxidation by plasma treatment (para. 1).
However, Fan establishes that polypropylene and COP are suitable equivalents which can be treated by oxygen plasma treatment (pg. 41, para. 00185). There is no teaching away from such material being utilized for this purpose and further evidence from Shahidzadeh supports the functionalization of polypropylene surfaces using such a technique and Kumar demonstrates that functionalized polypropylene surfaces are suitable for immobilization of oligonucleotides.
On page 5 of Applicant’s response, Applicant argues Shahidzadeh teaches that plasma treatment of polypropylene only produces peaks in the ketone/aldehyde region of the IR spectra after long treatment times and a subsequent washing step with a basic solution (para. 3). Applicant argues Gubala teaches against the use of longer plasma treatment times due to increased etching and fragmentation of the plastic material and that it is essential to bind molecules instantaneously after plasma treatment, due to the stability of surface reactive species (para. 3). On page 5 of Applicant’s response, Applicant argues Shahidazadeh fails to explicitly disclose that surface oxidation of polypropylene by plasma treatment can produce surface aldehyde groups and merely postulates aldehydes are formed (para. 4). There is no direct evidence that aldehydes are formed during the plasma treatment of a polypropylene substrate, thus a person of ordinary skill in the art would lack the motivation to replace COP with polypropylene (para. 4).
However, Shahidzadeh teaches aldehyde groups from of oxygen treated polypropylene after 30 seconds and refers to long treatment times of >10 seconds (pg. 280, figure 2, pg. 282, col. 2, para. 2). Whereas Gubala refers to long treatment times as greater than 2 minutes being unfavorable (pg. 545, figure 2B). Thus in order to facilitate formation of aldehydes on a polypropylene surface, a person of ordinary skill in the art would understand utilizing treatment times within this range. Shahidzadeh teaches basic solution washing was to increase the acidic character of the surface in this experiment, but it is not necessary for formation of aldehydes on the surface with oxygen plasma treatment (pg. 287, col. 1, para. 2, col. 2, para. 2). While Shahidzadeh does not specifically provide direct aldehyde group formation, a person of ordinary skill in the art upon the totality of the art relied upon, would understand that oxygen plasma generally results in the formation of such species, as is suggested by Shahidzadeh itself. Shahidzadeh establishes that oxygen plasma treatment of polypropylene surfaces and in view of Kumar and Fan, would serve as a suitable surface for conjugation of oligonucleotides via reaction with aldehyde species.
On page 6 of Applicant’s response, Applicant argues that neither Kumar or Fan remedy the deficiencies described above. Applicant argues Kumar is silent with regards to plasma treatment of a polypropylene surface (para. 2). Applicant argues Fan merely discloses polypropylene amongst an extensive list of exemplary materials and the use of plasma treatment is separately disclosed amongst a list of exemplary fabrication techniques and proves no motivation that these specific elements are compatible (para. 3). Applicant argues Fan is a generic disclosure (para. 3)
However, as discussed above, Fan establishes that polypropylene and COP are suitable equivalents which can be treated by oxygen plasma treatment (pg. 41, para. 00185). There is no teaching away from such material being utilized for this purpose and further evidence from Shahidzadeh supports the functionalization of polypropylene surfaces using such a technique and Kumar demonstrates that functionalized polypropylene surfaces are suitable for immobilization of oligonucleotides.
On pages 6-7 of Applicant’s response, Applicant argues a person of ordinary skill in the art would not have had any reasonable expectation of success in achieving surface aldehyde formation of a polypropylene surface using a plasma treatment method (bridging para.).
See response to arguments above, wherein utilizing a polypropylene surface for oxygen plasma treatment would be within the technical grasp of the skilled artisan attempting to practice the invention, given that the art establishes this material as viable surface for oxygen plasma treatment and subsequent conjugation to oligonucleotide/nucleic acids.
Applicant’s reply is considered to be a bona fide attempt at a response and is being accepted as a complete response. The 35 USC § 103 rejections and double patenting rejections are maintained for reason of record and foregoing discussion.
Conclusion
No claims are allowed in this action.
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 SAMUEL L GALSTER whose telephone number is (571)270-0933. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM.
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, Scarlett Y Goon can be reached at 571-270-5241. 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.
/S.L.G./Examiner, Art Unit 1693
/ANDREA OLSON/Primary Examiner, Art Unit 1693
Prosecution Insights