DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Preliminary Amendment and Status of the Claims
2. This action is in response to papers filed 10 April 2025 in which claims 1-14 were cancelled, the specification and claim 15 was amended, and new claims 16-33 were added. All of the amendments have been thoroughly reviewed and entered.
3. Claims 15-33 are under prosecution.
Specification
4. The use of trade names or marks used in commerce (including but not necessarily limited to Activator 42, InyLinker, and NittoPhase), has been noted in this application. Any trade names or marks should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Information Disclosure Statement
5. The Information Disclosure Statement filed 8 August 2024 is acknowledged and has been considered.
It is noted that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
6. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
7. Claim 25 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The word “preferably” in claim 25 is indefinite, as it is unclear if the “preferable” limitation is actually required.
Claim Rejections - 35 USC § 103
8. 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.
9. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
10. Claims 15-19, 23, and 33 are rejected under 35 U.S.C. 103 as obvious over Peyman et al. (U.S. Patent Application No. US 2002/0151512 A1, published 17 October 2002) and Okamoto et al. (U.S. Patent Application Publication No. US 2013/0289263 A1, published 31 October 2013).
Regarding claim 15, Peyman et al. teach methods for producing poly-G flanked (i.e., G-capped) oligonucleotides, wherein the oligonucleotides are 10 to 40 nucleotides long and comprise 7 or more (e.g., 10) consecutive guanine monomers at teach of the 5’ and 3’ termini, and wherein the oligonucleotides are chemically synthesized (Abstract, see also the second and third sequences under “22” on page 7 and claims 1 and 42 of Peyman et al.). The oligonucleotides are unmodified (paragraph 0007) and thus consist exclusively of phosphodiester bound oligonucleotides, and are also DNA molecules (e.g., paragraph 0033; see also paragraph 0010 [which shows oligos containing T, and thus are not RNA] and paragraph 0057 [which states the oligos are formed using a DNA synthesizer]), and thus are deoxy-oligonucleotide molecules. Peyman et al. further teach the synthesis of the molecules uses standard phosphoramidite chemistry and oxidation (paragraph 0057); thus, because the oligos start with multiple guanines, it would have been obvious to start with a guanosine phosphoramidite coupling to the first guanine nucleotide of the oligo being synthesized, followed by oxidation to produce a GG dinucleotide. In addition, because the oligos are 40 nucleotides long and use the standard phosphoramidite chemistry (Abstract and paragraph 0057), it would have been obvious to repeat steps of coupling a nucleoside phosphoramidite to the oligonucleotide, followed by oxidation of each resulting extension product for the claimed number of times to produce the claimed oligonucleotide. Peyman et al. also teach the methods produce oligonucleotides having the added advantage of being useful for treating diseases (paragraph 0047). Thus, Peyman et al. teach the known techniques discussed above.
It is noted that Peyman et al. also teach removal of protective groups (paragraph 0057), and the courts have held that selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946). See MPEP 2144.04 IV.C. Thus, any order of the deprotection is an obvious variant of the teachings of the prior art.
In addition, it is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
In addition, MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, counsel’s mere arguments cannot take the place of evidence in the record.
Peyman et al. do not explicitly teach the claimed coupling.
However, Okamoto et al. teach methods of forming deoxyoligonucleotides (i.e., DNA; paragraphs 0006 and 0153) having phosphodiester bonds (see page 2) wherein a nucleoside (i.e., formula G) is coupled to a phosphoramidite in a solution comprising a mixture of 1:1 mixture of DMF and acetonitrile, which is 50% DMF, as well as a tetrazole activating agent (paragraph 0189-0190), and that the methods have the added advantage of easily producing a probe containing a dye (paragraph 0056). Thus, Okamoto et al. teach the known techniques discussed above.
In addition, it is reiterated that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists.
Therefore, the claimed ranges merely represent an obvious variant of the values of the cited prior art.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Peyman et al. and Okamoto et al. to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantages of producing oligonucleotides useful for treating diseases as explicitly taught by Peyman et al. (paragraph 0047) and easily producing a probe containing a dye as explicitly taught by Peyman et al. (paragraph 0056). In addition, it would have been obvious to the ordinary artisan that the known techniques of Okamoto et al. and Peyman et al. could have been combined with predictable results because the known techniques of Okamoto et al. and Peyman et al. predictably result in reliable chemistry for forming useful oligonucleotides.
Regarding claims 16-19, the method of claim 15 is discussed above. Okamoto et al. teach the solvent is a 1:1 mixture of acetonitrile and DMF (i.e., claim 19; paragraph 0190), which is also in the ranges of claims 16-19.
In addition, it is reiterated that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists.
Therefore, the claimed ranges merely represent an obvious variant of the values of the cited prior art.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record.
Regarding claim 23, the method of claim 15 is discussed above. Peyman et al. teach the use of a support (e.g., CPC or Tentagel; paragraph 0057).
Regarding claim 33, the method of claim 15 is discussed above. Peyman et al. teach sequences having 10 guanines at each end (i.e., the CAPs) with an oligo of 10 bases in between (Abstract), which is 66.6% guanine.
In addition, it is reiterated that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists.
Therefore, the claimed ranges merely represent an obvious variant of the values of the cited prior art.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record.
11. Claims 20-22 are rejected under 35 U.S.C. 103 as obvious over Peyman et al. (U.S. Patent Application No. US 2002/0151512 A1, published 17 October 2002) and Okamoto et al. (U.S. Patent Application Publication No. US 2013/0289263 A1, published 31 October 2013), and as applied to claim 15 above, and further in combination with Cook et al. (U.S. Patent No. 6,528,631 B1, published 4 March 2003).
Regarding claims 20-22, the method of claim 15 is discussed above in Section 10.
Neither Okamoto et al. nor Peyman et al. specifically teach the solvent is only DMF.
However, Cook et al. teach phosphoramidite synthesis of oligonucleotides, wherein coupling of phosphoramidites (i.e., claim 22) is performed in DMF only (i.e., claims 20 and 22), using 5-methylthio-1H-tetrazole (Example 24). Cook et al. also teach the method has the added advantage of allowing incorporation of folate (Abstract), which is useful for increasing uptake of conjugates into cells (column 5, lines 1-20). Thus, Cook et al. teach the known techniques discussed above.
It is noted that the courts have stated:
similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Grabiak, 769 F.2d 729, 731, 226 USPQ 870, 871 (Fed. Cir. 1985) (“When chemical compounds have very close’ structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563 F.2d 457, 461, 195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d 1013, 1016, 173 USPQ 560, 562 (CCPA 1972) (see MPEP 2144.08(d)).
The courts have also stated:
[c]ompounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious) (see MPEP 2144.09).
Therefore, the use of the claimed 5-ethylthio-1H-tetrazole is an obvious variation over the 5-methylthio-1H-tetrazole of Cook et al. (i.e., claims 21-22; Example 24).
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the methods of Peyman et al. and Okamoto et al. with the teachings of taught by Cook et al. to arrive at the instantly claimed methods with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in methods having the added advantage of producing nucleic acids having increased uptake into cells as explicitly taught by Cook et al. (column 5, lines 1-20). In addition, it would have been obvious to the ordinary artisan that the known techniques of Cook et al. could have been combined with the methods of Peyman et al. and Okamoto et al. with predictable results because the known techniques of Cook et al. predictably result in molecules useful for cellular uptake.
12. Claims 21 and 23-24 are rejected under 35 U.S.C. 103 as obvious over Peyman et al. (U.S. Patent Application No. US 2002/0151512 A1, published 17 October 2002) and Okamoto et al. (U.S. Patent Application Publication No. US 2013/0289263 A1, published 31 October 2013) as applied to claims 15 and 23 above, and further in combination with Srivastava et al. (U.S. Patent Application Publication No. US 2011/0137010 A1, published 9 June 2011).
It is noted that while claims 21 and 23 ha been as described above, the claim is also obvious using the interpretation outlined below.
Regarding claims 21 and 23-24, the method of claim 15 is discussed above in Section 10.
While Peyman et al. teach the use of a CPC or Tentagel support (i.e., claim 23; paragraph 0057), neither Okamoto et al. nor Peyman et al. teach the functionally equivalent support of claim 24.
However, Srivastava et al. teach the synthesis of nucleic acids on a solid support using a universal support, in the form of divinylbenzene crosslinked polystyrene supports (paragraphs 0381-0382).
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record.
Srivastava et al. also teach the methods have the added advantage of using one of the most often used solid phase materials (paragraph 0381). Thus, Srivastava et al. teach the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the methods of Peyman et al. and Okamoto et al. with the functionally equivalent support taught by Srivastava et al. to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in methods having the added advantage of utilizing one of the most often used solid phase materials as explicitly taught by Srivastava et al. (paragraph 0381). In addition, it would have been obvious to the ordinary artisan that the known techniques of Srivastava et al. could have been combined with the method of Peyman et al. and Okamoto et al. with predictable results because the known techniques of Srivastava et al. predictably result in reliable chemistry for forming useful oligonucleotides.
13. Claim 25 is rejected under 35 U.S.C. 103 as obvious over Peyman et al. (U.S. Patent Application No. US 2002/0151512 A1, published 17 October 2002), Okamoto et al. (U.S. Patent Application Publication No. US 2013/0289263 A1, published 31 October 2013) Srivastava et al. (U.S. Patent Application Publication No. US 2011/0137010 A1, published 9 June 2011). as applied to claim 24 above, and further in combination with Ravikumar et al. (Org. Proc. Res. Devel., vol. 12, pages 399-410, published online 16 May 2008).
Regarding claim 25, the method of claim 24 is discussed above in Section 12.
None of the previously cited prior art teaches the claimed functionally equivalent linker.
However, Ravikumar et al. teach the synthesis of nucleic acids on a solid support
using the claimed universal linker (Figure 6). Ravikumar et al. also teach the support comprises a hydroxyl group (page 404), which becomes the O on the linker to X upon coupling the linker to the support. Ravikumar et al. also teach the linkers have the added advantage of allowing smooth and efficient synthesis (Abstract).
Thus, Ravikumar et al. teach the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of the previously cited prior art with the functionally equivalent linker taught by Ravikumar et al. to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantage of smoothly and efficiently producing nucleic acids as explicitly taught by Ravikumar et al. (Abstract). In addition, it would have been obvious to the ordinary artisan that the known techniques of Ravikumar et al. could have been combined with the previously cited prior art with predictable results because the known techniques of Ravikumar et al. predictable results in useful linkers for immobilizing nucleic acids.
14. Claims 26-33 are rejected under 35 U.S.C. 103 as obvious over Peyman et al. (U.S. Patent Application No. US 2002/0151512 A1, published 17 October 2002) and Okamoto et al. (U.S. Patent Application Publication No. US 2013/0289263 A1, published 31 October 2013) as applied to claim 15 above, and further in view of Bachmann et al. (U.S. Patent Application Publication No. US 2003/0099668 A1, published 29 May 2003).
It is noted that while claim 33 has been as described above, the claim is also obvious using the interpretation outlined below.
Regarding claims 26-33, the method of claim 15 is discussed above in Section 10.
While Peyman et al. teach four to ten guanosine entities at the 5’ and 3’ ends of oligonucleotides and having the claimed lengths (i.e., claims 26-33; Abstract and he second and third sequences under “22” on page 7), neither Peyman et al. nor Okamoto et al. teach SEQ ID NO:1, which meets the limitations of all of the listed claims.
However, Bachmann et al. teach SEQ ID NO:1 and that the nucleic acid has the added advantage of being immunostimulatory (Table 1, which follows paragraph 0380), and thus is ideal for therapeutic vaccination (Abstract). Thus, Bachmann et al. teach the known techniques discussed above
In addition, it is reiterated that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists.
Therefore, the claimed ranges (i.e., the 11 G residues at one end of SEQ ID NO:1) merely represent an obvious variant of the values of the cited prior art.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record.
It is also noted that each of SEQ ID Nos: 7-9 and 2 are contained withing DEQ ID NO:1.
It would therefore have been obvious to a person of ordinary skill in the art t before the effective filing date of the claimed invention to have used the methods of Okamoto et al. and Peyman et al. to synthesize SEQ ID NO:1 as taught by Bachmann et al. to arrive at the instantly claimed methods with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in methods having the added advantage of producing immunostimulatory nucleic acids that are ideal for therapeutic vaccination as explicitly taught by Bachmann et al. (Abstract and Table 1). In addition, it would have been obvious to the ordinary artisan that the known techniques of Bachmann et al. could have been combined with the methods of Okamoto et al. and Peyman et al. predictable results because the known techniques of Bachmann et al. predictably result in a sequence useful for preparing vaccines
Conclusion
15. No claim is allowed.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert T. Crow whose telephone number is (571)272-1113. The examiner can normally be reached M-F 8:00-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dave T. Nguyen can be reached on 571-272-0731. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Robert T. Crow
Primary Examiner
Art Unit 1634
/Robert T. Crow/Primary Examiner, Art Unit 1634
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