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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. JAPAN 2020-079572, filed on 04/28/2020.
Claim status
Claims 1-17 are pending. Claims 11-17 are withdrawn. Claim 18 is new. Claims 1-10 and 18 are examined herein.
Objections/Rejections
The rejection of claims 1-10 under 35 USC 103 is maintained.
The rejection of claim 18 is new.
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.
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, 4-10 are rejected under 35 U.S.C. 103 as being unpatentable over Takeuchi et al. (WO 2018221271) in view of Song et al. (Aptamer-based biosensors, Trends in Analytical Chemistry, Vol. 27, No. 2, 2008), Balamurugan et al. (Surface immobilization methods for aptamer diagnostic applications, Anal Bioanal Chem (2008) 390:1009–1021) and Reinemann et al. (US 20220112499) for reasons of record which are reiterated herein below.
Regarding claims 1 and 6, Takeuchi teaches an analytical sensor comprising a material having a substrate and a polymer film on the substrate (see page 2 lines 30 and 35-37). The polymer film has a concave portion (see page 4 line 30: teaching a plurality of concave portions on polymer film), an antibody substance binding group, and a signal substance binding group (see page 2 lines 35-37).
Additionally, the antibody substance binding group can bind to a variety of antibodies against target analytes (see page 1 lines 45-47). The signal substance binding group is a group capable of introducing a signal substance into the analytical sensor preparation substrate by binding a signal substance (see page 6 par.1). Also, the signal substance may already be bound to the signal substance binding group (see page 6 par.5).
However, Takeuchi does not teach that there is a polynucleotide group for nucleic acid aptamer's binding, and there is a nucleic acid aptamer bound to the polynucleotide group .
Song provides the advances in the development of aptamer-based biosensors and bioassay methods, most of which have employed electrochemical, optical and mass-sensitive analytical techniques (see Abstract). Song teaches that aptamers exhibit many advantages as recognition elements in biosensing when compared to traditional antibodies because they are small in size, chemically stable and cost effective. More importantly, aptamers offer remarkable flexibility and convenience in the design of their structures, which has led to novel biosensors that have exhibited high sensitivity and selectivity. See Abstract.
Particularly, aptamers often possess high selectivity and affinity toward their targets. In fact, aptamers bind to their targets with high affinity, particularly with macromolecules (e.g., proteins), which often possess remarkable dissociation constants (Kd) ranging from picomolar to nanomolar (see page 109 col.1 last par. and col.2 first par.).
In addition, Balamurugan reviews a various methods for the immobilization of aptamers onto different substrates, e.g., polymer (see Abstract). Particularly, the design of aptamers for surface immobilization includes a linker or spacer group connected to the terminal functional group (see page 1013 col.1 par.3, page 1018 Linkers section, and Fig.2-3). The function of the linker is to present the aptamer above the surface to promote accessibility of target analytes to the aptamer binding site (see page 1018 col.2 par.1).
Furthermore, Reinemann discloses a biosensor comprising an aptamer to a target analyte, wherein the aptamer is immobilized on the sensor thereof (see par.9-10, par.42). A support of the sensor can be a solid phase support (e.g., a base material) (see par.112). Also, the support may comprise a membrane made of polymer (see par.113). Reinemann further teaches that the immobilization aptamer may comprise a spacer molecule, e.g., a spacer molecule selected from a polynucleotide molecule (see par.107).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the sensor of Takeuchi, replacing the antibody substance binding group with a polynucleotide group for nucleic acid aptamer’s binding because of the following reasons. Song teaches aptamers exhibit many advantages as recognition elements in biosensing when compared to traditional antibodies because they are small in size, chemically stable and cost effective (see Song Abstract). Moreover, aptamer-based sensor is also high sensitivity and selectivity (see Song Abstract). Thus according to Song, aptamer and antibody are functionally equivalent but aptamer has more advanced features relative to antibody. Additionally, in order to immobilize an aptamer to a target analyte on the sensor surface, Balamurugan teaches that a linker or spacer group is needed to connected the aptamer to the terminal functional group, thereby to present the aptamer above the surface to promote accessibility of target analytes to the aptamer binding site (see discussion above). Further, Reinemann specifically teaches that a spacer can be a polynucleotide. Therefore, instead of using antibody to detect a target analyte, the sensor of Takeuchi can be modified to an aptamer-based sensor comprising a polynucleotide spacer, thereby the sensor would be chemically stable, cost effective, high sensitivity and selectivity.
The modified sensor of Takeuchi still encompasses the sensor in claim 6 because it comprises a nucleic acid aptamer and a signal substance already bound on the sensor.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining Takeuchi, Song, Balamurugan and Reinemann because they are directed to producing a sensor for analysis of a detection target.
Regarding claim 4, Takeuchi, Song, Balamurugan and Reinemann teach the invention as discussed above. Takeuchi further teaches that the polymer film is composed of a molecular imprinting polymer which is larger in size than the detection target as a template (see page 2 lines 38-39). Moreover, the concave portion corresponds to a part of the surface shape of the template (see page 4 lines 35-36).
Regarding claim 5, Takeuchi, Song, Balamurugan and Reinemann teach the invention as discussed above. Takeuchi further teaches that the signal substance binding group includes a thiol group (see page 6 lines 17-20).
Regarding claim 7, Takeuchi, Song, Balamurugan and Reinemann teach the invention as discussed above. Takeuchi further teaches a plurality of detection targets for the sensor such as microparticles having a membrane structure (see page 6 line 47).
Regarding claim 8, Takeuchi, Song, Balamurugan and Reinemann teach the invention as discussed above. Takeuchi further teaches that the membrane structures of a microparticle are exosomes, microvesicles, apoptosis corpuscles and the like (see page 6 lines 52-53).
Regarding claim 9, Takeuchi, Song, Balamurugan and Reinemann teach the invention as discussed above. They do not explicitly teach that the nucleic acid aptamer on the sensor for analysis of a detection target has a specific binding ability to a specific molecule expressed on a surface of the microparticle having a membrane structure.
As discussed in claim 1, the modified Takeuchi’s sensor comprises an aptamer to a target analyte. See discussion in claim 1 above. Takeuchi discloses the following feature. The antibody substance binding group on the polymer film binds to antibody specific to the detection target. The antibody specific to the detection target has a specific binding ability to a specific antigen expressed on the surface of the microparticle having the membrane structure. See page 2 lines 45-51.
Song and Balamurugan also teach that aptamers have been identified as binding tightly to a broad range of targets (e.g., proteins, peptides, amino acids, drugs, metal ions and even whole cells) (see at least Song page 108 col.1 par.3, Balamurugan page 1011 col.1 par.4). Balamurugan further teaches the target may be biomarkers that are overexpressed on cell membranes (see page 1011 col.2 par.1).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute an antibody in the sensor taught by Takeuchi, with an aptamer for a specific molecule expressed on a surface of the microparticle having a membrane structure, e.g., cell membrane antigen because the following reasons. Takeuchi teaches a sensor with an antibody to a specific antigen expressed on the surface of the microparticle having the membrane structure. Song and Balamurugan teaches that aptamer can also detect a target antigen on a cell membrane. Thus aptamer and antibody are functionally equivalent. The modified sensor of Takeuchi is still able to detect a specific antigen expressed on the surface of the microparticle having the membrane structure.
A person of ordinary skill in the art would have been motivated to replace an antibody with an aptamer for detecting membrane antigen because an aptamer has a high sensitivity with a chemically stable and cost effective as taught by Song in the abstract.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining Takeuchi, Song, Balamurugan and Reinemann because they are directed to producing a sensor for analysis of a detection target.
Regarding claim 10, Takeuchi, Song, Balamurugan and Reinemann teach the invention as discussed above. To analyze a detection target, Takeuchi teaches the following.
A sample containing a detection target is brought into contact with the analytical sensor, then the detection target binds to the antibody substance (see page 2 line 52). In the case of the modified sensor of Takeuchi, the detection target would bind to the nucleic acid aptamer on the sensor because the antibody substance is replaced by the aptamer.
In addition, the binding between the detection target and the capture agent, e.g., antibody or aptamer, is detected by the changing signal from the signal substance. See page 2 lines 51-54.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to expect the success in using the modified Takeuchi’s sensor to detect an analyte target because aptamer and antibody are functionally equivalent in terms of binding the target analyte with high specificity. Therefore, modifying an antibody to an aptamer for capturing a target analyte on the Takeuchi’s sensor would result in a predictable outcome.
Claims 2 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Takeuchi et al. (WO 2018221271) in view of Song et al. (Aptamer-based biosensors, Trends in Analytical Chemistry, Vol. 27, No. 2, 2008), Balamurugan et al. (Surface immobilization methods for aptamer diagnostic applications, Anal Bioanal Chem (2008) 390:1009–1021) and Reinemann et al. (US 20220112499), as applied in claim 1 above, and further in view of Sarmanthi (Difference Between Oligonucleotide and Polynucleotide, differencebetween.com, 2017, PTO-892 filed 03/12/2024).
Regarding claims 2 and 18, Takeuchi, Song, Balamurugan and Reinemann teach the invention as discussed above. The modified Takeuchi’s sensor does not clearly teach the length of the polynucleotide group.
However, the review of Balamurugan summarized important chemical protocols for the immobilization of aptamers and compared different approaches for the immobilization. Particular emphasis was placed on presenting examples involving the optimization of the linker design and immobilization procedures. This included the identity of the molecular structure of the linker, the length of the linker, and its point of attachment, all of which are necessary to place the aptamer above the surface in a “solution-like” environment for the optimum binding of target molecules. See Conclusion section.
Moreover, Reinemann supports that the length of linker is varied (see par.102-104: teaching that aptamers may be immobilized to a support via an immobilization oligonucleotide linker; see par.107: teaching the immobilization oligonucleotide comprising a polynucleotide group; see par.105: teaching the immobilization oligonucleotide having about 10 to 20 nucleotides in length, e.g. about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more nucleotides in length). This teaching encompasses the polynucleotide group for nucleic acid aptamer’s binding has a length more than 8 bases and in between 16-25 bases as in claims 2 and 18.
Furthermore, Sarmanthi discloses a definition of a polynucleotide in page 2, last paragraph. Accordingly, a polynucleotide molecule consists of 13 or more nucleotide monomers (page 1 par. 1 and page 2 par. 2).
Briefly, Balamurugan suggests that the length of the linker, i.e., the polynucleotide should be optimized in the immobilization procedure to present the aptamer above the surface for the optimum binding of target molecules and Reinemann suggests that the length of the polynucleotide group for nucleic acid aptamer’s binding can be more than 8 bases and from 16-20 bases or more.
It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980).
Since Applicant has not disclosed that the specific limitation recited in instant claim 2 (i.e., the polynucleotide has a length of 8 bases or more or from 16-25 bases) is for any particular purpose other than the polynucleotide is used as a linker to attach aptamer to a solid support, and the prior arts teach that the length of the polynucleotide often vary according to place the aptamer above the surface in a “solution-like” environment for the optimum binding of target molecules. Therefore, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the length of the polynucleotide spacer by normal optimization procedures known in the art.
Moreover, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to expect that the polynucleotide spacer for the nucleic acid aptamer binding in the modified Takeuchi’s sensor would have had a length of 8 bases or more, or had a length of 16 to 25 bases because it is a common property of a polynucleotide as taught by Sarmanthi. Also, it would help to present the aptamer above the sensor surface to bind to a target molecule.
One having an ordinary skill in the art would have had a reasonable expectation of success in using the polynucleotide having a length of 8 or more or 16-25 bases as the nucleic acid aptamer’s binding in the modified Takeuchi’s sensor because Reinemann supports that the linker having the length of 8 or more or 16-25 bases can be used to immobilize aptamer on the solid surface for detecting an analyte of interest.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Takeuchi et al. (WO 2018221271) in view of Song et al. (Aptamer-based biosensors, Trends in Analytical Chemistry, Vol. 27, No. 2, 2008), Balamurugan et al. (Surface immobilization methods for aptamer diagnostic applications, Anal Bioanal Chem (2008) 390:1009–1021) and Reinemann et al. (US 20220112499), as applied in claim 1 above, and further in view of Gopinath et al. (USP 11391734).
Regarding claim 3, Takeuchi, Song, Balamurugan and Reinemann teach the invention as discussed above. They fails to teach that a polynucleotide group is single chain.
However, Gopinath discloses an analyte detecting device comprising a polynucleotide platform and a functional molecule, i.e., a DNA aptamer (see Abstract, Summary par.2, and col.14 lines 61-62). Gopinath further teaches that the polynucleotide platform has a single chain (see col.2 lines 58-62 disclosing that the polynucleotide platform can be single - stranded DNA or single - stranded RNA). This teaching shows that the single chain polynucleotide – aptamer complex can be used in a biosensor to detect a target analyte.
For this reason, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the sensor taught by Takeuchi, including a single chain polynucleotide group for nucleic acid aptamer as taught by Gopinath because Gopinath teaches a single chain polynucleotide conjugated with aptamer can be used to detect a target molecule in a biosensor. The motivation to do so comes from Song because Song teaches that an aptamer-based sensor has a high sensitivity with a chemically stable and cost effective (see Song Abstract).
One having an ordinary skill in the art would have had a reasonable expectation of success in combining Takeuchi and Gopinath because they are directed to an optical biosensor to detect an analyte of interest (see Takeuchi page14 lines 10-15, Gopinath Abstract).
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1 and 4-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of copending Application No. 16617987 (‘987) in view of Song et al. (Aptamer-based biosensors, Trends in Analytical Chemistry, Vol. 27, No. 2, 2008), Balamurugan et al. (Surface immobilization methods for aptamer diagnostic applications, Anal Bioanal Chem (2008) 390:1009–1021) and Reinemann et al. (US 20220112499). Although the claims at issue are not identical, they are not patentably distinct from each other because the following reasons.
Regarding claim 1, claim 1 of ‘987 discloses a base material for producing a sensor for analysis of a detection target, comprising: a base material; and a polymer film provided on a surface of the base material, wherein the polymer film includes a concave that receives the detection target, and inside the concave is a group for binding antibody substance and a group for binding signal substance.
‘987 does not teach a polynucleotide group for nucleic acid aptamer.
However, Song, Balamurugan and Reinemann teach that a polynucleotide group for nucleic acid aptamer can be integrated into a biosensor as discussed above. See discussion of Song, Balamurugan and Reinemann in claim 1 above.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the sensor of ‘987, replacing the antibody substance binding group with a polynucleotide group for nucleic acid aptamer’s binding because of the following reasons. Song teaches aptamers exhibit many advantages as recognition elements in biosensing when compared to traditional antibodies because they are small in size, chemically stable and cost effective (see Song Abstract). Moreover, aptamer-based sensor is also high sensitivity and selectivity (see Song Abstract). Thus according to Song, aptamer and antibody are functionally equivalent but aptamer has more advanced features relative to antibody. Additionally, in order to immobilize an aptamer to a target analyte on the sensor surface, Balamurugan teaches that a linker or spacer group is needed to connected the aptamer to the terminal functional group, thereby to present the aptamer above the surface to promote accessibility of target analytes to the aptamer binding site (see discussion above). Further, Reinemann specifically teaches that a spacer can be a polynucleotide. Therefore, instead of using antibody to detect a target analyte, the sensor of Takeuchi can be modified to an aptamer-based sensor comprising a polynucleotide spacer, thereby the sensor would be chemically stable, cost effective, high sensitivity and selectivity.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining ‘987, Song, Balamurugan and Reinemann because they are directed to producing a sensor for analysis of a detection target.
Regarding claim 4, ‘987, Song, Balamurugan and Reinemann teach the invention as discussed above. Further, claim 2 of ‘987 teaches that the polymer film is composed of a molecularly imprinted polymer produced using the detection target or an object larger in size than the detection target as a template.
Regarding claim 5, 987, Song, Balamurugan and Reinemann teach the invention as discussed above. Further, claim 1 of ‘987 teaches that the group for binding signal substance is a thiol group.
Regarding claim 6, 987, Song, Balamurugan and Reinemann teach the invention as discussed above. Further, claim 3 of ‘987 encompasses the limitations of the claim because the modified sensor of ‘987 comprises a nucleic acid aptamer and a signal substance already bound on the sensor. . See discussion of claim 6 above.
Regarding claim 7, 987, Song, Balamurugan and Reinemann teach the invention as discussed above. Further, claim 4 of ‘987 teaches the detection target is a microparticle having a membrane structure.
Regarding claim 8, 987, Song, Balamurugan and Reinemann teach the invention as discussed above. Further, claim 5 of ‘987 encompasses the limitations of the claim.
Regarding claim 9, 987, Song, Balamurugan and Reinemann teach the invention as discussed above. Further, claim 6 of ‘987 encompasses the limitations of the claim. . See discussion of claim 9 above.
Regarding claim 10, 987, Song, Balamurugan and Reinemann teach the invention as discussed above. Further, claim 7 of ‘987 encompasses the limitations of the claim. See discussion of claim 10 above.
Claims 2 and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of copending Application No. 16617987 (‘987) in view of Song et al. (Aptamer-based biosensors, Trends in Analytical Chemistry, Vol. 27, No. 2, 2008), Balamurugan et al. (Surface immobilization methods for aptamer diagnostic applications, Anal Bioanal Chem (2008) 390:1009–1021) and Reinemann et al. (US 20220112499), as applied in claim 1 above, and further in view of Sarmanthi (Difference Between Oligonucleotide and Polynucleotide, differencebetween.com, 2017).
Regarding claims 2 and 18, ‘987, Song, Balamurugan and Reinemann teach the invention as discussed above. The modified ‘987’s sensor does not clearly teach the length of the polynucleotide group.
However, the review of Balamurugan summarized important chemical protocols for the immobilization of aptamers and compared different approaches for the immobilization. Particular emphasis was placed on presenting examples involving the optimization of the linker design and immobilization procedures. This included the identity of the molecular structure of the linker, the length of the linker, and its point of attachment, all of which are necessary to place the aptamer above the surface in a “solution-like” environment for the optimum binding of target molecules. See Conclusion section.
Moreover, Reinemann teaches that aptamers may be immobilized to a support via a linker sequence, e.g., immobilization oligonucleotide (see par.102-104). The immobilization oligonucleotide comprises a polynucleotide group (see par.107) and is between about 10 to about 20 nucleotides in length, e.g. about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more nucleotides in length (see par.105). This teaching encompasses the polynucleotide group for nucleic acid aptamer’s binding has a length more than 8 bases and in between 16-25 bases as in claims 2 and 18.
Furthermore, Sarmanthi discloses a definition of a polynucleotide in page 2, last paragraph. Accordingly, a polynucleotide molecule consists of 13 or more nucleotide monomers (page 1 par. 1 and page 2 par. 2).
While Balamurugan and Reinemann do not specifically teach the same length of the polynucleotide group for nucleic acid aptamer’s binding, Balamurugan suggests that the length of the linker, i.e., the polynucleotide should be optimized in the immobilization procedure and Reinemann suggests that the length of the polynucleotide group for nucleic acid aptamer’s binding can be more than 8 bases and from 16-20 bases.
It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980).
Since Applicant has not disclosed that the specific limitation recited in instant claim 2 (i.e., the polynucleotide has a length of 8 bases or more or from 16-25 bases) is for any particular purpose or solve any stated problem (e.g., the polynucleotide is used as a linker to attach aptamer to a solid support) and the prior arts teach that the length of the polynucleotide often vary according to place the aptamer above the surface in a “solution-like” environment for the optimum binding of target molecules. Therefore, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the length of the polynucleotide spacer by normal optimization procedures known in the art.
Moreover, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to expect that the polynucleotide spacer for the nucleic acid aptamer binding in the modified ‘987 sensor would have had a length of 8 bases or more, or had a length of 16 to 25 bases because it is a common property of a polynucleotide as taught by Sarmanthi. Also, it would help to present the aptamer above the sensor surface to bind to a target molecule.
One having an ordinary skill in the art would have had a reasonable expectation of success in using the polynucleotide having a length of 8 or more or 16-25 bases as the nucleic acid aptamer’s binding in the modified ‘987 sensor because Reinemann supports that the linker having the length of 8 or more or 16-25 bases can be used to immobilize aptamer on the solid surface for detecting an analyte of interest.
Claim 3 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of copending Application No. 16617987 (‘987) in view of Song et al. (Aptamer-based biosensors, Trends in Analytical Chemistry, Vol. 27, No. 2, 2008), Balamurugan et al. (Surface immobilization methods for aptamer diagnostic applications, Anal Bioanal Chem (2008) 390:1009–1021) and Reinemann et al. (US 20220112499), as applied in claim 1 above, and further in view of Gopinath et al. (USP 11391734).
Regarding claim 3, ‘987, Song, Balamurugan and Reinemann teach the invention as discussed above. They fails to teach that a polynucleotide group is single chain.
However, Gopinath discloses an analyte detecting device comprising a polynucleotide platform and a functional molecule, i.e., a DNA aptamer (see Abstract, Summary par.2, and col.14 lines 61-62). Gopinath further teaches that the polynucleotide platform has a single chain (see col.2 lines 58-62 disclosing that the polynucleotide platform can be single - stranded DNA or single - stranded RNA). This teaching shows that the single chain polynucleotide – aptamer complex can be used in a biosensor to detect a target analyte.
For this reason, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the sensor taught by ‘987, including a single chain polynucleotide group for nucleic acid aptamer as taught by Gopinath because Gopinath teaches a single chain polynucleotide conjugated with aptamer can be used to detect a target molecule in a biosensor. The motivation to do so comes from Song because Song teaches that an aptamer-based sensor has a high sensitivity with a chemically stable and cost effective (see Song Abstract).
One having an ordinary skill in the art would have had a reasonable expectation of success in combining ‘987 and Gopinath because they are directed to an optical biosensor to detect an analyte of interest (see Takeuchi page14 lines 10-15, Gopinath Abstract).
Response to Arguments
Applicant's arguments filed 07/11/2025 have been fully considered but they are not persuasive.
Applicant, in page 5 last paragraph and page 6 first paragraph, argued that “The teachings by Song et al. that aptamers have high sensitivity and selectivity and affinity, with Kd values ranging from picomolar to nanomolar is no different from the known properties of antibodies. Therefore, Song et al. provides no basis to believe that aptamers would uniquely function better in the context of the presently claimed material for producing a sensor for analysis of a detection target, compared to antibodies. There was certainly no basis to believe that, compared to antibodies, aptamers have significantly higher affinities for their corresponding detection target when they are introduced into the concave of the presently claimed sensory material.”
Applicant, in page 6 paragraphs 3-4, argued that “The Examiner takes the position that, since Song et al. teaches that "aptamers exhibit many advantages as recognition elements in biosensing when compared to traditional antibodies because they are small in size, chemically stable and cost effective", there was allegedly motivation to try an aptamer in place of the antibody of Takeuchi et al. However, there are limits on the level of increased sensitivity that those skilled in the art would have been able to predict when the sensing element is substituted from an antibody to an aptamer, based on the teachings of Song et al.”
These arguments have been fully considered but are not persuasive. First, Song does teach “the performance of the aptamer-modified CNT-FET provided better results than those obtained from the antibody-modified one under identical conditions” in page 112 right column lines 3-10. This teaching is derived from the cited reference 37 of Song. Applicant, in the Remarks page 7 paragraph 2, also acknowledges the better results taught by the cited reference 37 of Song, that is “the sensitivity of the aptamer-modified sensor is at most 10 times (one order of magnitude) higher than that of the antibody-modified sensor.” That means Song does teach the sensor using the aptamer is more sensitive than the sensor using antibody. Therefore, Song has a basis to believe that, compared to antibodies, aptamers have higher affinities for their corresponding detection target, so using the aptamer-modified sensor gives better result than using the antibody-modified sensor. Thus, the motivation of substituting aptamers for antibodies in a sensor, e.g., a concave shaped sensor, is for achieving a higher sensitive sensor.
Second, the significantly increase in order of magnitude of the aptamer-based biosensor in relative to the antibody-based biosensor is one reason (given by the Applicant and the Examiner) to substitute from an antibody to an aptamer into a biosensor. However, there are many other reasons (given by the Examiner) that those skilled in the art would have been motivated to introduce aptamers into a sensor in place of antibodies. Song teaches that aptamers exhibit many advantages as recognition elements in biosensing when compared to traditional antibodies because they are small in size, chemically stable and cost effective (see Song Abstract). Thus, the motivation of substituting aptamers for antibodies in a sensor, e.g., a concave shaped sensor, is also for achieving a stable and cost-effective sensor.
Applicant, in page 6 paragraph 2 and page 7, argued that “the present inventors surprisingly discovered that there is a significant synergistic relationship between aptamers and the presently claimed material for producing a sensor for analysis of a detection target. As presented in the Rule 132 declaration by Toshifumi Takeuchi, previously submitted, when antibody is introduced in the concave of the claimed sensor material, an affinity increase corresponding to 3 to 5 orders of Kd values is achieved, compared to before introduction in the concave. In contrast, when aptamers are introduced into the concave of the claimed sensor materials, a remarkably high increase in affinity equivalent to 8 to 10 orders of Kd values is achieved, compared to before the introduction in the concave…
In contrast, according to Table A of the experimental data in the Rule 132 Declaration by Toshifumi TAKEUCHI, dated December 5, 2024, submitted on December 9, 2024 in the response to the previous Final Office Action, the comparison between Comparative Example 2, Example 3 and the additional data shows that the aptamer immobilized in the micro concave of the material has a sensitivity increase of three orders of magnitude in Kd value compared to the antibody immobilized in the micro concave of the material.
This sensitivity increase is remarkable in light of the teaching of K. Maehashi, et al. (i.e., a sensitivity increase of only one order of magnitude) referenced by Song et al. This remarkable increase in sensitivity can be obtained because the claimed material for a sensor employs a specially shaped substrate (i.e., substrate with sensing elements in the micro concave) that has the ability to increase sensitivity by 8 to 10 orders by simply immobilizing aptamers in the micro concave (see paragraph 15 of the Rule 132 declaration by Toshifumi TAKEUCHI). There was no way that the person having ordinary skill in the art could have predicted such sensitivity increases.”
Examiner respectfully disagrees. First, the remarkable increase in sensitivity that the Applicant showed in the Rule 132 declaration is not recited in the claims. The cited prior arts still meets the claims because they teach all the recited components in the claims.
Second, while the person having ordinary skill in the art could not have predicted how much sensitivity the aptamer-based biosensor increases, e.g., one or 10 or more orders of magnitude, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to envision the better performance of the aptamer-based sensor as suggested by Song, wherein the better performance can come from the advantages of aptamers in recognizing elements (e.g., the sensitivity of the aptamer-modified sensor is at most 10 times higher than that of the antibody-modified sensor), being smaller in size, being chemically stable and being cost effective (see Song in Abstract and in page 112 right column lines 3-10). Since the prior art Song teaches that the sensitivity of the aptamer-modified sensor is improved compared to the antibody-based sensor, the modification would be obvious for one having skill in the art trying this known potential technique to improve similar device.
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.
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/CHAU N.B. TRAN/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 November 7, 2025
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