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 .
The claims dated 10/16/2025 are under consideration.
The amendments and arguments presented in the papers filed 3/8/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 12/16/2025 listed below have been reconsidered as indicated. The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
Information Disclosure Statement
The listing of or citation of references in the specification or the citation of references throughout 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 or cited on a submitted IDS, they have not been considered.
Drawings
The drawings dated 2/3/2022 include sequences. The sequences presented in the Figures are identified in the specification starting on page 17.
Claim Interpretation
Claim 3 recites “at least (≥)”. The symbol “≥” in the parenthetical is understood to be short hand for “at least”, i.e. greater than or equal to.
Claim 7 is interpreted as requiring: 1) “the first variable sequence tract V1 differs from the second variable tract V2 in length”; and/or 2) “the base sequence and/or composition of the first variable sequence tract V1 differs from the base sequence and/or composition of the second variable sequence tract V2 in at least one position”.
Claim 10 is interpreted as describing the structure of the probe sequence P in regards to what hybridizes with it.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-10 and 12 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Mullins (WO 95/01453).
The following rejections have been maintained
Regarding claim 1, Mullins teaches a method that produces the results in Figure 2E (which distinguishes between different nucleic acid sequences based on electrophoretic mobility) and that involves heteroduplex analysis carried out with gap-containing heteroduplex molecules (p. 12, lines 20-24).
Mullins teaches when two divergent sequences are mixed and hybridized to form heteroduplex molecules, mobility shifts in polyacrylamide gels was observed. The heteroduplexes contain various internal gaps. See Figure 2E; p. 17, lines 1-18.
Mullins teaches the heteroduplexes were formed from a number of HIV-1 fragments from different source materials that were amplified and fragments having divergent sequences were identified (p. 17, 16-26).
Based on sequence comparisons, three HIV-1 fragments having internal deletions (i.e., deletions in HIV-1 sequences) of 9 base pairs were identified (9, Figure 2E; and p. 17, lines 23-26). These HIV-1 amplification fragments having internal deletions of 9 base pairs are encompassed by the broad scope of “probe sequence P”, which is simply complementary to 5’ and 3’ portions of first nucleic acid sequence S1 and second nucleic acid sequence S2.
The Heteroduplexes were formed between:
1) the HIV-1 fragments having internal deletions 9 base pairs as probes; and
2) the normal fragments, i.e., those not containing a deletion, as encompassed by “first nucleic acid sequence S1” having a V1 sequence of 9 bases”; and/or those with a 3 base pair internal deletion having a V2 sequence of 3 base pairs as encompassed by “second nucleic acid sequence S2”.
On p. 49, HIV-1 fragments were named and are mapped to the claims as follows:
“Probe” – MA311 or MA6, each having a 9 bp central deletion
“first nucleic acid sequence S1” – insertion fragments or the “normal sequence”
“second nucleic acid sequence S2” – MA21, having a 3 bp central deletion
The “first nucleic acid sequence S1” and “second nucleic acid sequence S2” of Mullins identified above have length that varies by 6 nucleotides.
Because the deletions are centrally located, each of the of the Mullins “S1” and “S2” have a C1 and C2 and a C1’ and a C2’, respectively, located at the 5’ and 3’ ends. These 5’ and 3’ ends are identical to one another. The “probe” of Mullins includes a RC1 and RC2 that hybridizes with these 5’ and 3’ ends of S1 and S2.
Because the “probes” of Mullins are amplification products, they are double stranded. This is further evidenced by the fact that amplification products are combined, denatured and renatured (p. 23, lines 7-17; p. 40, lines 2-6; and p. 63, lines 28-32).
The heteroduplexes are resolved using electrophoresis and polyacrylamide gels (p. 12, line 23-24), which is relevant to the step of “subsequently submitting the first and second probe hybrids to electrophoresis and detecting the electrophoretic mobility of the first and second probe hybrid”, thereby distinguishing between the first and second nucleic acid sequences. See Fig. 2E, distinguishing between different sequences via an electrophoretic gel.
See also p. 49, line 1 to p. 50, line 6.
Regarding claim 2, Mullins teaches the amplification products have a length of 704 base pairs, and some with deletions of 3 or 9 base pairs (p. 49, lines 9-21).
Regarding claim 3, the length of C1, C2, C1’ and C2’ are not defined in the claim. The “S1” and “S2” of Mullins have sufficient length so as to have the structure described in claim 3. For example, when C1 and C1’ start at position 10 of the 704 base pair amplification product, there are 9 nucleotides 5’ of C1 and C1’. Similarly, when C2 and C2’ end at position 694 of the 704 base pair amplification product, there are 9 nucleotides 3’ of C2 and C2’.
Regarding claim 4, because Mullins teaches the amplification products having a length of 704 base pairs as noted above, the combined length of the C1 and C2 tracts is between 18 and 3500 nucleotides.
Regarding claim 5, Mullins teaches the amplification products having a length of 704 base pairs as noted above having centrally located deletions or “insertions” in the case of the “normal” sequence. Thus, the 5’ and 3’ flanking sequences have a ratio between 1:7 and 7:1, in particular roughly around a 1:1 ratio.
Regarding claim 6, Mullins teaches insertion fragments or “normal” fragments which individually each have a “V1” or a “V2” that is 9 base pairs as noted above.
Regarding claims 7 and 8, Mullins teaches the insertion fragment or “normal” fragment as “S1” having a “V1” of 9 nucleotides and MA21 as “S2” having a “V2” of 3 nucleotides. This results in a length difference of 6 nucleotides as encompassed by claim 8.
Regarding claim 9, Mullins teaches the composition of the “V1” and “V2” described in the rejections of claim 7 and 8 differs in 2 positions, i.e., two of the 6 nucleotides deleted between them.
Regarding claim 10, Mullins teaches double stranded “S1” and “S2” that are amplification products that are denatured as described above. Thus, “S1” and “S2” are hybridized to their reverse complements prior to denaturing.
Regarding claim 12, Mullins teaches denaturing and renaturing as noted above. The ordinary artisan would recognize the denaturing occurs at a temperature above the melting temperature of hybridized nucleic acids and renaturing occurs at a temperature below the melting temperature of two nucleic acids.
The Examiner’s response to the traversal of the 102 rejections
The Remarks argue the cited reference does not teach all of the claimed elements, and so cannot and does not anticipate the instant claims and repeats the language of claim 1 (p. 2-3). The Remarks argue Mullins does not disclose "A method for distinguishing a first nucleic acid sequence from a second nucleic acid sequence by electrophoresis" because there is no such step of distinguishing two nucleic acids described in Mullins (p. 3).
The arguments have been fully considered but are not persuasive. Claim 1 is drawn to a method for “distinguishing a first nucleic acid sequence from a second nucleic acid sequence by electrophoresis”; however, the active method steps do not explicitly require an active method step of “distinguishing a first nucleic acid sequence from a second nucleic acid sequence by electrophoresis”. MPEP 2111.02 states:
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention's limitations, then the preamble is not considered a limitation and is of no significance to claim construction.
Accordingly, the claim language of "distinguishing a first nucleic acid sequence from a second nucleic acid sequence by electrophoresis" merely sets forth the intended use or purpose of the claimed methods, but does not limit the scope of the claims. The claims are given the broadest reasonable interpretation as requiring:
contacting the first nucleic acid sequence and the second nucleic acid sequence with a probe sequence P as defined in the claim under conditions allowing the hybridization of the probe sequence to the first and second nucleic acid sequence;
subsequently submitting the first and second probe hybrids to electrophoresis; and
detecting the electrophoretic mobility of the first and second probe hybrid.
The claims states the “contacting” step results in “forming a first probe hybrid and a second probe hybrid”. Mullins teaches each of these above steps.
Even if the claim was amended to require an active method step of "distinguishing a first nucleic acid sequence from a second nucleic acid sequence by electrophoresis", it is noted that Mullins does teach distinguishing between the first and second nucleic acid sequences using electrophoresis. See Fig. 2E, distinguishing between different sequences via an electrophoretic gel. Mullins further teaches distinguishing nucleic acid sequences based on genetic distance as reflected in heteroduplex mobility.
The Remarks further argue the subject matter of claim 1 is not disclosed in Mullins because if one sequence with a 9 base pair (bp) deletion is considered the "probe" of claim 1 and the sequence without this deletion is considered "the first nucleic acid sequence", there is no "second nucleic acid sequence". The Remarks argue the 3bp and 9bp deletions are distributed over the full length sequence of the HIV gene and there is only a first nucleic acid sequence and no corresponding second nucleic acid sequence, which would have the C1' and C2' part as the probe and the first nucleic acid sequence and a different V2 than V1, which is not present in the probe sequence. See p. 3.
The arguments have been fully considered but are not persuasive. Mullins teaches heteroduplexes were formed between:
1) the HIV-1 fragments having internal deletions 9 base pairs as probes; and the normal fragments, i.e., those not containing a deletion, as encompassed by “first nucleic acid sequence S1” having a V1 sequence of 9 bases”; and
2) the HIV-1 fragments having internal deletions 9 base pairs as probes; and fragments with a 3 base pair internal deletion having a V2 sequence of 3 base pairs as encompassed by “second nucleic acid sequence S2”.
On p. 49, HIV-1 fragments were named and are mapped to the claims as follows:
“Probe” – MA311 or MA6, each having a 9 bp central deletion;
“first nucleic acid sequence S1” – insertion fragments or the “normal sequence”
“second nucleic acid sequence S2” – MA21, having a 3 bp central deletion
The “first nucleic acid sequence S1” and “second nucleic acid sequence S2” of Mullins identified above have length that varies by 6 nucleotides and the V1 and V2 regions are represented as insertions relative to the 9 bp deletion. In other words, the first and second nucleic acid sequences of Mullins have a “gap” between the C1/C1’ and C2/C2’ reflected by the insertions of 6 or 9 nucleotides relative to the 9 bp deletion in the MA311 or MA6 sequence. Mullins further teaches the results indicate the mobility of the heteroduplexes is affected by the sequence that is "looped out" of the "insertion" sequence relative to the "deletion" sequence (p. 17-18). This is analogous to what happens in when a target has a looped out region after hybridization with a probe as depicted in Figure 1b of the present application.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682
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