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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/28/2025 has been entered.
Regarding the Office action mailed 07/29/2025:
The claim objections (including the precautionary objections regarding claims that at that time were withdrawn from consideration) are withdrawn in view of the amendment.
All rejections under 35 USC 103 are withdrawn based upon the exclusion of the Bergmann reference under 35 USC 102(b)(2)(C).
The non-statutory double patenting rejection over co-pending application 17/126,439 is maintained and reiterated below. In addition, new grounds of rejection are set forth below. Applicant’s arguments will be addressed following the rejections.
Election/Restrictions
All previous restrictions in this application are withdrawn, as all claims require elements found to be free of the prior art (notwithstanding the non-statutory double patenting rejection) based upon ongoing amendments during prosecution. All claims are rejoined.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, all previous restriction requirements in this application are hereby withdrawn as to the currently pending claims. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claim Objections
Claims 10, 15 and 17 are objected to because of the following informalities:
Claim 10, last line, should say “…the first member of the binding pair…” for clarity.
Claims 15 and 17, part (c) should read “…coupled to an an .
Appropriate correction is required.
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, 2, 4, 8-11, 15-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 12 of co-pending Application No. 17/126,439 in view of Angione (US 2018/0149656). Claim 12 of the ‘439 application discloses selection of a binding pair composed of beta-L-LNA oligomers.
Angione showed how complementary oligonucleotides could be used as binding partners in an immunoassay. Specifically, one oligonucleotide was biotinylated and immobilized on a streptavidin-modified support, and the other oligonucleotide was conjugated to an antibody capable of binding to an analyte (see Figure 1). Note that during such assay, the solid phase would be in contact with an aqueous liquid phase, as recited in claim 8, which contained the conjugate comprising the other oligonucleotide, as recited in claim 9.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the application to use the beta-L-LNA binding pair disclosed by ‘439 claim 12 as shown in Angione, as one of ordinary skill in the art would have realized this to be an art-recognized use for complementary oligos.
This is a provisional nonstatutory double patenting rejection.
Claims 5-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 12 of co-pending Application No. 17/126,439 in view of Angione (US 2018/0149656) as applied to claims 1, 2, 4, 8-11, 15-21 above, and further in view of Lee (US 2020/0354677).
The disclosure of ‘439 claim 12 and Angione have been discussed. In addition, it is noted that Angione disclosed the solid phase could be magnetic beads (para 0038, 0044).
Lee disclosed the use of monodisperse (para 0180, 0193) paramagnetic beads (para 0011, 0102), having diameters of about 4.5 micron (which is about 3 micron) (para 0011), as solid phase for attaching antibody (para 0102).
It would have been obvious to one or ordinary skill in the art prior to the effective filing date of the application to use monodisperse paramagnetic beads as disclosed by Lee as the solid support for use of the LNA oligomer binding partners of ‘439 claim 12 in the immunoassay of Angione, as this represents nothing more than selecting an art-recognized material based on suitability for its intended purpose (MPEP 2144.07).
Claims 12-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 12 of co-pending Application No. 17/126,439 in view of Angione (US 2018/0149656) as applied to claims 1, 2, 4, 8-11, 15-21 above, and further in view of Polansky (US 2004/0023207).
‘439 claim 12 and Angione have been discussed.
Polansky taught (paragraph [0919]): “Well known advantages of commercial kits include convenience and reproducibility due to manufacturing standardization, quality control and validation procedures.”
It would have been obvious to put the components suggested by the combined teachings of ‘439 claim 12 and Angione into a kit to obtain the advantages of kits disclosed by Polansky.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 4-9, 11-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Each of these claims requires the limitation “and wherein no member of the binding pair is capable of hybridizing with a naturally-occurring single-stranded nucleic acid”. As a preliminary matter, this language is confusing as it is unclear if the basis for this property is intended to mean that the claimed binding pair cannot bind to natural sequences because the sequences of the members of the binding pair do not match the sequence of any naturally-occurring nucleic acid. Alternatively, it could be that the basis for the recited property is intended to mean that β-L-LNA cannot, by its nature, hybridize to natural nucleic acids due to a chemical incompatibility. In either case, the claims lack adequate written description.
As to the first possible meaning of the recited property, this would mean the claims encompass the genus of all β-L-LNA for which the sequences1 do not occur in nature. It is not possible for anyone to know what falls within this genus, because one cannot know that a sequence does NOT occur in nature. One can only know that it DOES occur in nature, by virtue of discovering such sequence in naturally occurring nucleic acid.
As to the second possible meaning of the recited property, it is noted that Kumar (2009) demonstrates that β-L-LNA can, in fact, hybridize to complementary, natural DNA and RNA (natural in the “chemical” sense). See page 2397, column 1, paragraph 1: “Thus, ‘β-L-LNA’ was found to form stable duplexes with both pRNA and pDNA but not with apRNA and apDNA.” By “p” is meant parallel, whereas “ap” stands for anti-parallel. Kumar also demonstrates this property of β-L-LNA to hybridize to natural RNA and DNA, albeit in parallel rather than anti-parallel fashion; see Table 2, ON4. Therefore, Applicant is not in possession of β-L-LNA that is incapable of hybridizing to “natural” nucleic acid.
The easiest way to overcome this rejection, as well as clear up the confusion of what is meant by “and wherein no member of the binding pair is capable of hybridizing with a naturally-occurring single-stranded nucleic acid”, is to simply strike this language from the claim, as the claims are already limited to binding pairs that consist of β-L-LNA.
Response to Arguments
Applicant's arguments filed 10/28/2025 have been fully considered but they are not persuasive.
Applicant argues (in section A, starting on page 11 of the reply) that the ‘439 application “teaches away” from the claimed invention. This is based on Applicant pointing to a particular example in the ‘439 application (Example 2, section c) in which a particular pair of LNA oligos did NOT form a duplex. The title of this section is “identification of sequence which forms duplex slowly”. However, immediately above is a section (Example 2, section b) titled “identification of sequence which forms duplex fast”, and discloses a pair of LNA oligomers that form a duplex quickly (and one of the oligos was biotinylated). Figures 3 and 4 of the application demonstrates successful duplex formation of this pair of oligos either with (Fig 4) or without (Fig 3) prior denaturation (page 19, Description of the Figures). Applicant ignores this fact to support a narrative that the ‘439 application would discourage one of ordinary skill in the art from considering a β-L-LNA binding pair as suitable for the purposes of Angione’s immunoassay platform. It is noted that ‘439 claim 12 is directed to a “method for providing a binding pair”. Surely, Applicant does not dispute that his own claim in his own co-pending application is enabled, and the underlying evidence in the specification indicates the claim is enabled to identify sequences that would function as desired. Therefore, this argument is not persuasive.
Applicant argues (section B, on page 13 of the reply) that the Office’s articulated reasoning does not account for the “teaching away evidence”. This is because, as noted above, the ‘439 application does not teach away from the claimed invention.
Applicant argues (section C, page 14 of the reply) that “[t]he instant claims include numerous structural and functional features not disclosed in claim 12 of the ‘439 Application of supplied by Angione”. Applicant presents a list of features, and then proceeds to point out which features are not taught by ‘439 claim 12, and which features are not taught by Angione. This amounts to a piecemeal analysis of the references. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The list of features recited by Applicant would result from applying the LNA binding pair of ‘439 claim 12 to the immunoassay of Angione. With particular regard to the feature of “an overcoating architecture designed to resist biotin interference”, this language is not present in the claims, nor would it be understood to require any particular “overcoating structure” beyond “a solid phase coated with (strept)avidin” as recited in the claim. Angione provides a solid phase coated with streptavidin (Fig 1, para 0008: “the solid surface is functionalized with (or coated with) streptavidin”). Therefore, this argument is not persuasive.
Applicant argues (section D, page 14 of the reply) “[w]hile the Advisory Action correctly notes that ‘the fact that two inventions may address different problems or have different goals’ does not alone establish patentability, this factor is relevant to the obviousness analysis when combined with teaching away evidence.” As noted above, there is no teaching away in the ‘439 application. There is merely recognition that not all LNA sequences rapidly form a duplex. However, the ‘439 application provides an enabled method for selecting LNA sequences that do.
Applicant argues (section E, page 15 of the reply) that there would not have been a reasonable expectation of success. This argument, like many above, is built upon the false contention that the ‘439 application “teaches away”. This argument is not persuasive because the ‘439 application shows that one can make a pair of LNA oligomers (including biotinylated oligos) that form a duplex that is fast and that does not require prior denaturation. There would have been a very reasonable expectation of success in obtaining a binding pair for use in the immunoassay of Angione.
Finally, Applicant argues (section F, page 15 of the reply) that the claims achieve “unexpected results”. Applicant argues: “Example 13 demonstrates that "formation of L-LNA oligonucleotide binding pairs is not affected by interference by free biotin," showing no signal loss at biotin concentrations of 100- 2000 ng/ml where conventional assays exhibited significant loss. This result was unexpected given the '439 application's teaching that biotinylated beta-L-LNA achieves only 5% duplex formation and fails selection criteria. The unexpected resistance to biotin interference combined with functional hybridization despite teaching away constitutes objective evidence of nonobviousness.” This argument is not persuasive, because as pointed out above, the ‘439 application also provides for biotinylated LNA binding pairs that do achieve duplex formation. In addition, Example 13 (of the instant application) fails to evidence that the lack of biotin interference is due specifically to the use of β-L-LNA oligos, as opposed to any other type of complementary nucleic acid.
For the reasons outlined above, Applicant’s arguments are not persuasive, and the double patenting rejection is maintained. The rejection has also been extended to previously withdrawn claims that would also have resulted from using β-L-LNA oligos obtained by the method of ‘439 claim 12 as the complementary oligos in Angione’s method.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL C WOOLWINE whose telephone number is (571)272-1144. The examiner can normally be reached 9am-5:30pm.
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/SAMUEL C WOOLWINE/ Primary Examiner, Art Unit 1681
1 It is understood that β-L-LNA does not occur in nature. The examiner is referring, however, to the base sequence, not the chemical structure.