DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application is being examined under the pre-AIA first to invent provisions.
Preliminary Amendment and Status of the Claims
2. The preliminary amendment filed 9 October 2023 in which the specification was amended, claims 1-57 were cancelled and new 58-77 claims were added have been thoroughly reviewed and entered.
3. Claims 58-77 are under prosecution.
Information Disclosure Statement
4. The Information Disclosure Statements filed 25 August 2025 and 23 July 2025 are acknowledged and have 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
5. 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.
6. Claims 58-77 are 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.
Claims 58 (upon which claims 60-77 depend) and 59 each recite “where in the solvent is,” which lack antecedent basis in the previous recitation of “at least one solvent.”
Claim Rejections - 35 USC § 103
7. The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
8. Claims 58-77 are rejected under pre-AIA 35 U.S.C. 103(a) as obvious over Matthiesen (PCT International Publication No. WO 2010/097656 A1, published 2 September 2010).
Regarding claim 58, Matthiesen teaches methods of hybridizing a nucleic acid comprising providing a first nucleic acid, a second nucleic acid, and a hybridization composition comprising a solvent which denatures double-stranded nucleic acids sequences, and allowing the hybridization of the first and second nucleic acid sequences in the presence of the composition for a period of time (page 9). Matthiesen also teaches butadiene dioxide and 2-pyrrolidone (claim 16 of Matthiesen).
With respect to tetramethylene sulfoxide, the final structure listed on page 7 of Matthiesen teaches a compound where Y is S, Z is not present, and X is O, and A and B are part of the alkyldiyl. Matthiesen does not explicitly teach the length of the alkyldiyl group, but does teach it is an unsaturated hydrocarbon (page 12).
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).
Thus, the claimed compound has a five carbon ring, which is an obvious variant of the prior art.
In addition, Matthiesen also teach tetrahydrothiapyran oxide, which is a one carbon homolog (i.e., six membered ring) of the instantly claimed (five membered ring) compound, and thus is an obvious variant based on the citation above.
It is further 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)).
Thus, the substitution of the claimed five membered sulfoxide for the six membered sulfoxide is an obvious variation of the prior art.
The courts have also 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 combining the first and second nucleic acids with the hybridization composition is obvious.
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 that cannot take the place of evidence in the record.
Regarding claim 59, Matthiesen teaches methods of hybridizing a nucleic acid comprising providing a first nucleic acid in an in situ biological sample (page 10), including FISH (page 4) and providing a second nucleic acid, and a hybridization composition comprising a solvent which denatures double-stranded nucleic acids sequences, and allowing the hybridization of the first and second nucleic acid sequences in the presence of the composition for a period of time (page 9). Matthiesen also teaches the methods have the added advantage of increasing specificity (page 3). Matthiesen also teaches butadiene dioxide and 2-pyrrolidone (claim 16 of Matthiesen).
With respect to tetramethylene sulfoxide, the final structure listed on page 7 of Matthiesen teaches a compound where Y is S, Z is not present, and X is O, and A and B are part of the alkyldiyl. Matthiesen does not explicitly teach the length of the alkyldiyl group, but does teach it is an unsaturated hydrocarbon (page 12).
In addition, Matthiesen also teach tetrahydrothiapyran oxide, which is a one carbon homolog (i.e., six membered ring) of the instantly claimed (five membered ring) compound,
It is reiterated that the courts have stated that:
A. Similar properties may normally be presumed when compounds are very close in structure;
B. Compounds which are homologs are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties; and
C. Selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results.
Thus, the claimed compound has a five carbon ring, which is an obvious variant of the prior art structure on page 7 of Matthiesen, and/or the substitution of the claimed five membered sulfoxide for the six membered sulfoxide is an obvious variation of the prior art, and any order of combining the first and second nucleic acids with the hybridization composition is obvious.
Applicant is again cautioned to avoid merely relying upon counsel' s arguments in place of evidence in the record.
Regarding claims 60-62, the method of claim 58 is discussed above. Matthiesen also teaches suppling heat energy, using a heat wire, to hybridize the nucleic acids (page 9).
In addition, with respect to claim 60, it is noted that the subject matter of a properly construed claim is defined by the terms that limit its scope. It is this subject matter that must be examined. As a general matter, the grammar and intended meaning of terms used in a claim will dictate whether the language limits the claim scope. Language that suggests or makes optional but does not require steps to be performed or does not limit a claim to a particular structure does not limit the scope of a claim or claim limitation. “Wherein” clauses are examples of language that may raise a question as to the limiting effect of the language in a claim. See MPEP 2103 I.C. and MPEP § 2111.04.
It is also noted that the courts have held that optimization through routine experimentation, and in particular, when related to differences in temperature, do not support patentability (In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)). Thus, the claimed manipulations of temperature are obvious variants merely representing routine optimization of the teachings of the cited prior art.
Applicant is again cautioned to not merely rely upon counsel’s arguments in place of evidence in the record.
Regarding claim 63, the method of claim 58 is discussed above. Matthiesen teaches the first nucleic acid (i.e., probe) is double stranded (page 33) and the second nucleic acid is the sample nucleic acid and is single stranded (pages 10-11).
Regarding claim 64, the method of claim 58 is discussed above. Matthiesen teaches a step of denaturing followed by a step of combining (i.e., hybridization; page 9).
Regarding claim 65, the method of claim 58 is discussed above. Matthiesen teaches steps of heating and cooling the combined (i.e., hybridization) composition and nucleic acid sequences (page 9).
In addition, with respect to claims 64 and 65, it is reiterated that the courts have held that any order of steps of the prior art is obvious.
Applicant is again cautioned to avoid merely relying upon counsel' s arguments in place of evidence in the record.
Regarding claims 66-70, the method of claim 58 is discussed above. Matthiesen teaches hybridization times of 4 minutes (page 37).
Regarding claims 71-74, the method of claim 58 is discussed above. Matthiesen teaches the “step of method of the invention includes the steps of heating and cooling (page 9), and that the denaturing of binding and hybridization occurs in less than 5 minutes (page 9). Thus, it would have been obvious for the binding reaction, which includes steps of cooling and heating, to occur in less than five minutes, thus resulting in a cooling step of less than 5 minutes.
Further, with respect to claims 66-74, 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 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),” including with respect to temperature as discussed above. See MPEP 2144.05 II.
Therefore, the claimed ranges alternatively represent routine optimization and/or an obvious variant of the values taught by the prior art.
Applicant is again cautioned to avoid merely relying upon counsel' s arguments in place of evidence in the record.
Regarding claim 75, the method of claim 58 is discussed above. Matthiesen teaches the claimed temperature values for denaturation (page 37).
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, and that the courts have 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 particular when related to temperature.
Therefore, the claimed temperature merely represents routine optimization and/or an obvious variant of the values taught by the prior art.
Applicant is reminded to not merely rely upon counsel’s arguments in place of evidence in the record.
Regarding claims 76-77, the method of claim 58 is discussed above. Matthiesen teaches the first nucleic acid is in a sample in the form of a histology sample (page 28).
Double Patenting
9. 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.
10. Claims 58-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-52 of U.S. Patent No. 9,297,035 B2 in view of Matthiesen (PCT International Publication No. WO 2010/097656 A1, published 2 September 2010).
Both sets of claims are drawn to methods of hybridizing nucleic acids using hybridization compositions and additional nucleic acids. Any additional limitations of the ‘035 claims are encompassed by the open claim language “comprising” found in the instant claims.
The ‘035 claims do not require the claimed functionally equivalent solvents.
However, the claimed solvents and the additional claimed limitations are taught by the prior art of Matthiesen as discussed above, and that the methods reduce and/or eliminate the uses of formamide (Abstract). Thus, Matthiesen teaches 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 modified the ‘035 claims with the teachings of Matthiesen to arrive at the instantly claimed methods with a reasonable expectation of success. The ordinary artisan would have been motivated to make the modification because said modification would have resulted in methods having the added advantage of reducing and/or eliminating the use of formamide as explicitly taught by Matthiesen (Abstract). In addition, it would have been obvious to the ordinary artisan that the known techniques of Matthiesen could have been applied to the ‘035 claims with predictable results because the known techniques of Matthiesen predictably result in use of functionally equivalent solvents for hybridization.
11. Claims 58-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-54 of U.S. Patent No. 9,303,287 B2 in view of Matthiesen (PCT International Publication No. WO 2010/097656 A1, published 2 September 2010).
Both sets of claims are drawn to methods of hybridizing nucleic acids using hybridization compositions and additional nucleic acids. Any additional limitations of the ‘287 claims are encompassed by the open claim language “comprising” found in the instant claims.
The ‘287 claims do not require the claimed functionally equivalent solvents.
However, the claimed solvents, the additional claimed limitations, and the rationale for combining are taught by the prior art of Matthiesen as discussed above.
12. Claims 58-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-61 of U.S. Patent No. 9,309,562 B2 in view of Matthiesen (PCT International Publication No. WO 2010/097656 A1, published 2 September 2010).
Both sets of claims are drawn to methods of hybridizing nucleic acids using hybridization compositions and additional nucleic acids. Any additional limitations of the ‘562 claims are encompassed by the open claim language “comprising” found in the instant claims.
The ‘562 claims do not require the claimed functionally equivalent solvents.
However, the claimed solvents, the additional claimed limitations, and the rationale for combining are taught by the prior art of Matthiesen as discussed above.
13. Claims 58-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 9,388,456 B2 in view of Matthiesen (PCT International Publication No. WO 2010/097656 A1, published 2 September 2010).
Both sets of claims are drawn to methods of hybridizing nucleic acids using hybridization compositions and additional nucleic acids. Any additional limitations of the ‘456 claims are encompassed by the open claim language “comprising” found in the instant claims.
The ‘456 claims do not require the claimed functionally equivalent solvents.
However, the claimed solvents, the additional claimed limitations, and the rationale for combining are taught by the prior art of Matthiesen as discussed above.
14. Claims 58-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,202,638 B2 in view of Matthiesen (PCT International Publication No. WO 2010/097656 A1, published 2 September 2010).
Both sets of claims are drawn to methods of hybridizing nucleic acids using hybridization compositions and additional nucleic acids. Any additional limitations of the ‘638 claims are encompassed by the open claim language “comprising” found in the instant claims.
The ‘638 claims do not require the claimed functionally equivalent solvents.
However, the claimed solvents, the additional claimed limitations, and the rationale for combining are taught by the prior art of Matthiesen as discussed above.
15. Claims 58-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of U.S. Patent No. 10,662,465 B2 in view of Matthiesen (PCT International Publication No. WO 2010/097656 A1, published 2 September 2010).
Both sets of claims are drawn to methods of hybridizing nucleic acids using hybridization compositions and additional nucleic acids. Any additional limitations of the ‘465 claims are encompassed by the open claim language “comprising” found in the instant claims.
The ‘465 claims do not require the claimed functionally equivalent solvents.
However, the claimed solvents, the additional claimed limitations, and the rationale for combining are taught by the prior art of Matthiesen as discussed above.
16. Claims 58-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 11,118,214 B2 in view of Matthiesen (PCT International Publication No. WO 2010/097656 A1, published 2 September 2010).
Both sets of claims are drawn to hybridization compositions and additional nucleic acids. Any additional limitations of the ‘214 claims are encompassed by the open claim language “comprising” found in the instant claims.
The ‘214 claims do not require the claimed method steps or functionally equivalent solvents.
However, the claimed solvents, the additional claimed limitations, and the rationale for combining are taught by the prior art of Matthiesen as discussed above.
17. Claims 58-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 11,118,226 B2 in view of Matthiesen (PCT International Publication No. WO 2010/097656 A1, published 2 September 2010).
Both sets of claims are drawn to hybridization compositions and additional nucleic acids. Any additional limitations of the ‘226 claims are encompassed by the open claim language “comprising” found in the instant claims.
The ‘226 claims do not require the claimed method steps or functionally equivalent solvents.
However, the claimed solvents, the additional claimed limitations, and the rationale for combining are taught by the prior art of Matthiesen as discussed above.
It is noted that the instant Application is not a divisional of the parent application of the ‘226 parent; therefore, the nonstatutory double patenting rejections are proper.
18. Claims 58-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,795,499 B2 in view of Matthiesen (PCT International Publication No. WO 2010/097656 A1, published 2 September 2010).
Both sets of claims are drawn to methods of hybridizing nucleic acids using hybridization compositions and additional nucleic acids. Any additional limitations of the ‘499 claims are encompassed by the open claim language “comprising” found in the instant claims.
The ‘499 claims do not require the claimed functionally equivalent solvents.
However, the claimed solvents, the additional claimed limitations, and the rationale for combining are taught by the prior art of Matthiesen as discussed above.
19. Claims 58-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,834,703 B2 in view of Matthiesen (PCT International Publication No. WO 2010/097656 A1, published 2 September 2010).
Both sets of claims are drawn to hybridization compositions and additional nucleic acids. Any additional limitations of the ‘703 claims are encompassed by the open claim language “comprising” found in the instant claims.
The ‘703 claims do not require the claimed method steps or functionally equivalent solvents.
However, the claimed solvents, the additional claimed limitations, and the rationale for combining are taught by the prior art of Matthiesen as discussed above.
20. Claims 58-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12,209,276 B2 in view of Matthiesen (PCT International Publication No. WO 2010/097656 A1, published 2 September 2010).
Both sets of claims are drawn to hybridization compositions and additional nucleic acids. Any additional limitations of the ‘276 claims are encompassed by the open claim language “comprising” found in the instant claims.
The ‘276 claims do not require the claimed method steps or functionally equivalent solvents.
However, the claimed solvents, the additional claimed limitations, and the rationale for combining are taught by the prior art of Matthiesen as discussed above.
21. Claims 58-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,534,755 B2 (formerly Application No. 17/588,023) in view of Matthiesen (PCT International Publication No. WO 2010/097656 A1, published 2 September 2010).
Both sets of claims are drawn methods of hybridizing nucleic acids using hybridization compositions and additional nucleic acids. Any additional limitations of the ‘755 claims are encompassed by the open claim language “comprising” found in the instant claims.
The ‘755 claims do not require the claimed functionally equivalent solvents.
However, the claimed solvents, the additional claimed limitations, and the rationale for combining are taught by the prior art of Matthiesen as discussed above.
22. Claims 58-77 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 61-74 of copending Application No. 19/035,623 in view of in view of Matthiesen (PCT International Publication No. WO 2010/097656 A1, published 2 September 2010).
Both sets of claims are drawn to hybridization compositions and additional nucleic acids. Any additional limitations of the ‘623 claims are encompassed by the open claim language “comprising” found in the instant claims.
The ‘623 claims do not require the claimed functionally equivalent solvents.
However, the claimed solvents, the additional claimed limitations, and the rationale for combining are taught by the prior art of Matthiesen as discussed above.
This is a provisional nonstatutory double patenting rejection.
Prior Art
23. The following prior art is hereby made of record, but not presently relied upon for any rejection, as it is considered pertinent to Applicant's disclosure.
Van Ness et al. (U.S. Patent No. 5,106,730) claims a method of hybridizing nucleic acids using 2-pyrrolidone (claim 7 of Van Ness).
Conclusion
24. No claim is allowed.
25. 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.
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, Anne Gussow can be reached at 571-272-6047. 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.
Robert T. Crow
Primary Examiner
Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683