DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/13/2025 has been entered.
Claims 23-25 have been canceled. Claims 38-39 have been added. Claims 22, 26-27, and 30-31 remain withdrawn. Claims 21, 28, and 32-39 are pending and are examined on the merits herein.
Response to Applicant’s Amendments
Claim Objections
Claims 32, 33, and 37 were objected to due to various informalities. In light of Applicant’s amendments to the claims submitted 10/13/2025, the objections for claims 32 and 37 have been withdrawn. The objection for claim 33 has been maintained-in-part, as Applicant did not address all of the objections presented in the Final Rejection. It is noted that Applicant has not argued against this objection in their Remarks. See also new grounds of objection below.
35 USC 112(b) Rejections
Claims 25 and 36-37 were rejected for various indefiniteness issues. Claim 25 has been canceled, and so this rejection has been rendered moot. In light of Applicant’s amendments to the claims submitted 10/13/2025, the rejections for claims 36-37 have been withdrawn. See also new grounds of rejection below.
35 USC 103 Rejections
Claims 21, 23-25, 28, and 32-37 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lee et al. (WO 2008/089193 A2) in view of Yu et al. (Bioinformatics, 2011) and various combinations of references. In light of Applicant’s amendments to the claims submitted 10/13/2025, these rejections have been withdrawn for all currently pending claims, but see “Response to Applicant’s Arguments” and new grounds of rejection below. Claims 23-25 have been canceled, and so these rejections have been rendered moot.
Response to Applicant’s Arguments
Regarding the 35 USC 103 Rejections presented in the previous Final Rejection, Applicant reiterates the allegedly unexpected results associated with their invention, and notes that none of the cited references provide motivation or a reasonable expectation of success in arriving at the claimed invention. Particularly, Applicant notes the results of Examples 1 and 3 in the instant specification, as well as data presented in previous Remarks. In the newly amended claims, Applicant states that each combination of primers in newly amended claim 21 is represented by these unexpected results, and Example 3 in particular shows that promotor sequences do not affect cycle times or the performance of primers. Applicant states, “The cycle times and performance are due to the second target-hybridizing sequences contained in these oligomers,” (Remarks, page 8). Applicant also argues that Example 3 provides similarly unexpected results with regard to three primer combinations, as are shown in instant claim 32 (Remarks, page 9).
Instant claim 21 requires the use of one of SEQ ID NOs: 78/79/80/81/83 and one of SEQ ID NOs: 108/109/111/112, where the sequences are for use together and where a 5’ promoter is attached to the second sequence. In Table 3 of the instant specification, SEQ ID NOs: 108/109/111/112 are noted to be the target-hybridizing regions of SEQ ID NOs: 88/89/91/92, where these longer sequences do have a 5’ promoter region attached. It is noted that the instant claims do not require a particular promoter sequence however, and so the second parvovirus amplification oligomer is not considered to solely encompass one of SEQ ID NOs: 88/89/91/92, though these sequences are considered to be within the scope of the claim.
In evaluating the examples in the instant specification, Example 1 is not currently relevant to claim 21, as the example is focused on sequences related to hepatitis and not parvovirus. Example 3 evaluates each combination of SEQ ID NOs: 75-87 (which contain no promoters) with SEQ ID NOs: 88-99 (which do contain promoters). Sensitivity down to 5 copies/mL of the target was found for combinations of SEQ ID NOs: 80 and 92, 80 and 91, and 81 and 92, though there was some variation depending on parvovirus genotype examined (paras. 268-269). As noted in previous actions, these data alone do not show unexpected results, as these results are not compared to those generated with the use of other primer pairs. It is presumed that these combinations exhibited the most sensitivity compared to the larger group of primer pairs, as para. 268 says “a number of combinations of amplification oligomers were identified that are useful for a parvovirus amplification reaction that amplifies as few as 10 copies of parvovirus,” but the specific properties of SEQ ID NOs: 80 and 92, 80 and 91, and 81 and 92 that led them to be considered “useful” is not stated. This evidence could be persuasive of unexpected results if the superior qualities of the primer pairs SEQ ID NOs: 80 and 92, 80 and 91, and 81 and 92 were clearly defined as compared to the other primer pairs examined.
In relating this to the instant claims, this evidence alone is not persuasive to render claim 21 as non-obvious over the prior art. The claim would need to be amended to recite only those pairs examined in para. 269, and additional data comparing the performance of these primers to the other combinations of SEQ ID NOs: 75-87 with each of SEQ ID NOs: 88-99 would be required.
Para. 270 describes combinations of three primers, where SEQ ID NOs: 80, 90, and 99, 80, 91, and 99, 80, 92, and 99, and 81, 91, and 99 all exhibited superior reactivity compared to the other combinations examined. This is considered sufficient to show a critical property of these primer combinations. Para. 271 then goes on to examine the three primer combinations of SEQ ID NOs: 80, 91, and 99, 80, 92, and 99, and 82, 90, and 99 on SEQ ID NOs: 200-202. It is noted that according to Table 3 and para. 269, SEQ ID NOs: 200-202 are simply parvovirus target sequences, and are not primers that are used for comparison. SEQ ID NOs: 82, 90, and 99 do not appear to be evaluated in para. 270, and so do not have the same reactivity comparisons as are shown for the other three primer combinations. While para. 271 shows that these three primer combinations can detect parvovirus when only a small amount is present in a sample, as these results are not compared to results of other primer combinations, it is unclear if these results are critical/unexpected.
In relating these conclusions to the instant claims, instant claim 32 recites three, three primer combinations. Two of these, SEQ ID NOs: 80, 91, and 99, and 80, 92, and 99, were described in para. 270, while SEQ ID NOs: 82, 90, and 99 was only described in para. 271. Thus, the claim as a whole cannot be said to be drawn to primers that exhibit critical/unexpected results. If the claim were amended to recite only the three primer combinations recited in para. 270 that showed superior results as compared to the other combinations (i.e. SEQ ID NOs: 80, 90, and 99, 80, 91, and 99, 80, 92, and 99, and 81, 91, and 99), then the provided evidence would likely be enough to render the claim non-obvious over the prior art.
Applicant also references pages 8-12 of their Remarks submitted 3/20/2025 to show data detailing additional alleged unexpected results. SEQ ID NOs: 78-80 and 83 shown align with the same SEQ ID NOs used in the instant application. However, SEQ ID NOs: 108-113 shown in the table of sequences in the Remarks do not appear to align with the corresponding SEQ ID NOs of the instant application. SEQ ID NOs: 108-113 in the Remarks instead appear to correspond to instant SEQ ID NOS: 88-93, respectively. Thus, these sequences represent instant SEQ ID NOs: 108-113 with particular promoter sequences attached. On pages 10-11 of these same Remarks, the data presented show that pairing each of instant SEQ ID NOs: 78, 79, 80, and 83 with each of instant SEQ ID NOs: 88, 89, 91, and 92 (SEQ ID NOs: 108, 109, 111, and 112 as listed in the data) resulted in unexpectedly short cycle times. These results are compared to those obtained from using other primer pairs, and do demonstrate superior performance over said other pairs. This data may be enough to demonstrate unexpected results.
In relating these results to the instant claims, these results are not currently commensurate in scope with instant claim 21. Firstly, instant claim 21 includes SEQ ID NO: 81, which does not appear in Applicant’s additional data. Furthermore, as noted above, instant claim 21 does not only encompass the promoter sequences recited in SEQ ID NOs: 88, 89, 91, and 92, as the claim recites the use of SEQ ID NOs: 108, 109, 111, or 112 with any promoter sequence. Instant claim 38 specifically recites use of SEQ ID NOs: 88, 89, 91, and 92, but also includes SEQ ID NO: 81 as an option for the first amplification oligomer, and so is also not commensurate in scope with the additional data. It is noted that above in Example 3, SEQ ID NO: 81 may be considered as part of critical combinations when used with SEQ ID NO: 92 (though additional data is required) or with SEQ ID NOs: 91 and 99 in a three primer combination. Applicant is encouraged to keep this in mind when amending the claims, and to consider specifying in future independent claims what sequences SEQ ID NO: 81 must be used with, if Applicant intends to keep this sequence in the claims.
Additionally regarding the scope of the claimed invention, it is noted that claim 21 is drawn to a particular combination of oligomers, and thus is a product. However, the product comprises the listed oligomers, even if the listed oligomers themselves are recited with closed language (i.e. “consists of”). Thus, additional components, such as additional oligomers, may be included in the composition, and it is unknown if any potential additionally encompassed components/oligomers would affect the results described by Applicant. Thus, it is recommended to recite the claimed composition with closed language (i.e. “said oligomer combination consisting of…”). Such a change would considerably narrow the scope of the claim. Concerning how this change may affect the dependent claims, for claim 28, this claim additionally requires the use of SEQ ID NO: 119, which according to Table 3 of the instant specification, is SEQ ID NO: 99 without the promoter sequence. SEQ ID NO: 99 is used in combinations of primers described above as potentially critical, and so it is recommended to either incorporate SEQ ID NO: 99 into claim 21 or recite a new independent claim including its use in a closed composition with other relevant primers disclosed as potentially critical above. Similarly for claim 32, this claim may be better rewritten as an independent claim that recites the triple primer combinations described as potentially critical above. Claim 33 is described separately below. Claims 34-37 would likely not need to be altered, as they include the precisely claimed invention of claim 21. Claim 38 is similar to claim 21, with the only change being that the second parvovirus oligomers now have specific promoter sequences. This claim may not be necessary if claim 21 is amended to significantly overlap in scope with claim 38. Claim 39 is also described separately below. It is stated for the record that these are only recommended claim amendments, and Applicant is free to amend the instant claims in any manner desired in future correspondence.
In the interest of compact prosecution, consideration of the above-described parvovirus primers with hepatitis A virus primers, as recited in claim 33, will be discussed. In the working examples of the instant specification, these two viruses only appear to be discussed together in Example 7, where it appears that hepatitis A virus oligomers and parvovirus oligomers were analyzed separately (para. 280). This example also does not appear to focus on the potentially critical/superior oligomer sequences for parvovirus described above. Thus, it is recommended that in instant claim 33, it be specified that the HAV primers are to be used separately from the parvovirus primers, so that the inclusion of these sequences into the invention does not render Applicant’s results concerning the parvovirus primers not commensurate in scope with claim 33. In considering this guidance in view of the guidance provided in the preceding paragraph, it is recommended to rewrite claim 33 as an independent claim, where the oligomer combination consists of two closed groups of oligomers (one for parvovirus and one for hepatitis A), where the groups of oligomers are specified to be packaged and used separately. Since these claims are still product claims, in order to ensure this use is not considered intended use, it is recommended that this use be written so as to impart structure to the claim. See MPEP 2111.02 II. Claim 39 specifically recites the use of both the parvovirus and hepatitis oligomers together, and so without data or explanation provided from Applicant, it is unclear if such a method would be commensurate in scope with the results currently provided by Applicant.
In considering the previous combination of references cited in the Final Rejection, in combining Lee in view of Yu, it is noted that in para. 26 of the Final Rejection, both a motivation (“In view of this, the ordinary artisan would have been motivated to use the commercially available software disclosed in Yu and the known human parvovirus sequences and primers disclosed by Lee to design additional primers for use in the method, kit, and reaction mixture of Lee, and in the absence of unexpected results, the claimed primers (instant SEQ ID NOs: 179-180 and 78-81, 83, 108-109, 111-112, and 119) simply represent the result of an obvious series of steps… Additionally, as Lee does not put a limit on the number of primers that may be provided in their kit, the ordinary artisan would be motivated to include multiple primers, as using multiple primer sequences would increase the chance that a target viral nucleic acid could be detected, which would be important in diagnostic and other medical contexts.”) and a reasonable expectation of success (“As Lee teaches means of amplification and detection using their primer sequences, there would be a reasonable expectation of success in using these sequences to perform the method of Lee and in arriving at the amplification oligomers of the claimed invention.”) are provided. Applicant has not provided any specific deficiencies in this rejection rationale, and so the rejection is considered proper.
Overall, Applicant’s arguments are not considered persuasive. New grounds of rejection are provided below to address Applicant’s amendments to the claims, and previously set forth teachings and rejections that remain relevant are reiterated below.
Claim Objections
Claim 33 is objected to because of the following informalities: Applicant should ensure that each instance of “(III)” includes the appropriate parentheses. In the final two wherein clauses of the claim, an additional opening parenthesis appears. Appropriate correction is required.
Claim 36 is objected to because of the following informalities: the claim uses the terminology “human parvovirus target nucleic acid” in the preamble. It is recommended that throughout the claim, wherever “parvovirus” appears, it should be amended to “human parvovirus.” Appropriate correction is required.
Claim 37 is objected to because of the following informalities: it is recommended that in lines 1-2, the wherein clause read “wherein the detection of the human parvovirus amplification product” to better match the language of the detecting step of claim 36, from which this claim depends. Appropriate correction is required.
Claim 39 is objected to because of the following informalities: the claim uses the terminology “human parvovirus target nucleic acid” in the preamble. It is recommended that throughout the claim, wherever “parvovirus” appears, it should be amended to “human parvovirus.” Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 21, 28 and 32-39 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.
Claim 21 is rejected because the structure of the second parvovirus amplification oligomer is contradictory. Specifically, it is stated that the oligomer “consists of” a second target-hybridizing sequence, meaning no additional components can be added to the oligomer. However, it is then stated that a promoter is attached to the second target-hybridizing sequence, which is considered an additional component. The metes and bound of the oligomer are therefore unclear.
Claims 28 and 32-39 are rejected due to their direct or indirect dependence on rejection claim 21.
Claim 32 is also rejected because the language is unclear. The claim states the use of multiple third oligomers, when it appears that only one is recited in the claim. It is recommended that “third amplification oligomers” read “a third amplification oligomer consisting of the sequence of SEQ ID NO: 99”, as this appears to be the only third oligomer recited in the claim. For additional clarity, it is also recommended that in the wherein clause read “wherein the oligomer combination comprises the following first amplification oligomer, second amplification oligomer, and third amplification oligomer, respectively:” Additionally, it is noted that one of the options for the second amplification oligomer, SEQ ID NO: 90, corresponds to instant SEQ ID NO: 110 with an attached promoter sequence (see Table 3 of the instant specification). However, SEQ ID NO: 110 is not one of the options for the second parvovirus amplification oligomer in claim 21, making the use of this sequence indefinite.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 32 and 38 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
As noted above in the 35 USC 112(b) Rejections, claim 32 includes a sequence for the second parvovirus amplification oligomer that is not based on any of the sequences encompassed by this oligomer in claim 21, from which this claim depends. Therefore, claim 32 does not include all the limitations of the claim upon which it depends.
Claim 38 is rejected because it states in (b) that the second parvovirus amplification oligomer consists of one of a particular group of sequences. However, claim 21, from which this claim depends, has been amended to state in (b) that the initial second parvovirus amplification oligomer consists of one of a particular group of sequences. The sequences recited in (b) of claim 38 include the sequences from (b) of claim 21, but also add additional nucleotides. Therefore, the options for the second parvovirus amplification oligomer in claim 38 do not include all of the limitations established for the second parvovirus amplification oligomer in claim 21, and so this claim is an improper dependent claim.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Interpretation
In claim 21, it is stated that the first and second amplification oligomers are used in combination. However, the claim is directed to a product. As this claimed use does not impart any structure to the oligomer combination, it is considered intended use, and therefore the prior art does not need to teach the use of the oligomers in combination in order to read on the instant claims. See MPEP 2111.02 II.
For each of the claimed amplification oligomers that comprises a target-hybridizing sequence that either comprises or consists of a particular sequence, it is noted that the amplification oligomer itself can still contain additional sequences outside of the target-hybridizing sequence.
Regarding claim 35, a “reaction mixture” is not specifically defined in the instant specification, and so is not considered to require more than the oligomer combination of claim 21.
Claim Rejections - 35 USC § 103
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 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 negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 21, 28, and 34-37 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lee et al. (WO 2008/089193 A2) in view of Yu et al. (Bioinformatics, 2011).
Lee teaches nucleic acid molecules derived from parvovirus B19 (Abstract). These molecules include primers and probes (e.g. page 15, para. 3 and page 16, para. 2). Two such molecules are SEQ ID NOs: 34 and 36, which are capable of amplifying parvovirus B19 nucleic acid in a sample (pages 10-11, under step (a)(i)). SEQ ID NO: 36 contains the sequences of instant SEQ ID NOs: 108 and 111. Lee also teaches SEQ ID NO: 128, which is a partial parvovirus B19 genomic sequence (page 13, para. 1). This sequence contains instant SEQ ID NOs: 78-81, 83, 108-109, 111-112, and 119. Lee also teaches the use of kits containing the primers of their invention, where primers may be designed from SEQ ID NO: 128 (page 21, para. 2), or from other disclosed sequences (page 32, para. 3; instant claim 34). This reference also teaches real-time PCR and notes that this may be performed quantitatively. In this PCR method, samples with viral nucleic acids are used and combined with amplification reagents in a tube or plate, and detection of amplicons occurs during the various amplification cycles (Example 2, pages 34-35; instant claims 36-37). Lee also teaches the use of multiplex assays (page 23, para. 2), and notes that the kit contains at least one primer and probe, indicating that multiple primers (and multiple primer pairs) may be used (page 21, para. 3).
Furthermore, Lee also teaches the use of promoters for isolated nucleic acids. These promoters can be artificially attached to the nucleic acid molecules (pages 25-26, joining para.). Isolated nucleic acids of their invention may be sequences short enough to be used as primers (see pages 5 and 8), can hybridize to a parvovirus genomic sequence (page 9, paras. 1-4), and can be obtained by PCR (page 25, para. 2) or used in amplification (page 27, para. 5 and page 28, para. 2). Lee teaches that promoters may be T7 promoters (page 27, para. 5). Figure 8 of the reference also shows a promoter on the 5’ end of a sequence. The promoter sequence may be used as a polymerase recognition site (page 26, para. 1).
Yu teaches a method using PriSM software where panels of primer pairs can be designed from known sequences, and particularly from known viral genomes (page 267, column 1, para. 4). These primer pairs can be used for amplification, and specifically PCR (page 267, column 1, paras. 3-4).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious to use the sequences described by Lee as amplification oligomers to arrive at the inventions of claims 21, 28, and 35. The teachings of Yu indicate that software for PCR primer design is available and can be used by the ordinary artisan to obtain multiple primers suitable for amplifying a known sequence (page 267, column 1, paras. 3-4). In view of this, the ordinary artisan would have been motivated to use the commercially available software disclosed in Yu and the known human parvovirus sequences and primers disclosed by Lee to design additional primers for use in the method, kit, and reaction mixture of Lee, and in the absence of unexpected results, the claimed primers (instant SEQ ID NOs: 78-81, 83, 108-109, 111-112, and 119) simply represent the result of an obvious series of steps. Lee already teaches the use of primers that include the sequences of SEQ ID NOs: 108 and 111, and teaches that their SEQ ID NO: 128 can be used to develop further primers, which would allow the ordinary artisan to arrive at SEQ ID NOs: 78-81, 83, 109, 112, and 119. Additionally, as Lee does not put a limit on the number of primers that may be provided in their kit, the ordinary artisan would be motivated to include multiple primers, as using multiple primer sequences would increase the chance that a target viral nucleic acid could be detected, which would be important in diagnostic and other medical contexts. As Lee teaches means of amplification and detection using their primer sequences, there would be a reasonable expectation of success in using these sequences to perform the method of Lee and in arriving at the amplification oligomers of the claimed invention.
Furthermore, in view of the promoter teachings of Lee described above, it would be prima facie obvious to combine any of the primer sequences described above by Lee in view of Yu with a promoter sequence – namely because said addition may lead to increased polymerase binding and therefore greater amplification yield, which would be motivating to the ordinary artisan. Lee teaches that the addition of promoters to nucleic acids related to viral genomes and amplification/detection is well-known, thus providing a reasonable expectation of success.
Therefore, claims 21, 28, and 34-37 are prima facie obvious over Lee in view of Yu.
Claims 32 and 38 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lee et al. (WO 2008/089193 A2), in view of Yu et al. (Bioinformatics, 2011), and further in view of Brentano et al. (US 2008/0274449 A1).
Regarding claim 32, Lee in view of Yu teaches the use of instant SEQ ID NO: 80, as described above. Regarding instant SEQ ID NOS: 90-92 and 99, these correspond to instant SEQ ID NOs: 110-112 and 119, respectively, with the addition of a T7 promoter (see Table 3) of the instant specification. Lee in view of Yu also already teaches instant SEQ ID NOs: 111-112 and 119, as described above. The T7 promoter region in the instant claims is 5’-aatttaatac gactcactat agggaga-3’ based on the comparisons of the instant SEQ ID NOs with and without promoter sequences.
Brentano teaches oligomers for detecting human parvovirus B19 genomic DNA (Abstract). The reference teaches the 5’ promoter of SEQ ID NO: 19, which is equivalent to the T7 promoter region of the instant application described above (para. 10). The reference teaches that any sequence can be modified to include a 5’ promoter sequence (para. 25), and that the promoter primer can be useful for reverse transcription purposes, similar to the teachings described by Lee above (para. 40). In para. 61, Brentano teaches amplifying a parvovirus B19 sequence with a primer that contains a target specific portion and the promoter of SEQ ID NO: 19.
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to use the teachings of Brentano to use the specific promoter of SEQ ID NO: 19 as the T7 promoter in Lee in view of Yu. This would amount to simple substitution of a particular promoter sequence. MPEP 2143 I (B) states, “The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art.” This results of this substitution would be successful amplification of a human parvovirus B19 sequence, as Brentano already teaches the use of this promoter sequence in such a fashion, and so would be predictable. Thus, this combination of references would result in the use of SEQ ID NOs: 91, 92, and 99, as this promoter could be added to SEQ ID NOs: 111, 112, and 119 described above.
Thus, claim 32 is prima facie obvious over Lee, in view of Yu, and further in view of Brentano.
Regarding claim 38, as Lee in view of Yu, and further in view of Brentano described above teaches the use of SEQ ID NOs: 78-81, 83, 91, and 92, these references also read on this claim.
Claims 33 and 39 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lee et al. (WO 2008/089193 A2), in view of Yu et al. (Bioinformatics, 2011), and further in view of Carlson et al. (U.S. Patent Application Publication No. 2006/0014142 A1) in view of Pichuantes et al. (U.S. Patent No. 6,942,965 B2), and in view of Zhang et al. (Chinese Patent Application No. 101875942 A).
Regarding claims 33 and 39, Lee in view of Yu teaches the oligomer combination of claim 21. However, neither of these references teach measuring parvovirus and HAV nucleic acids.
Carlson teaches in vitro methods for amplifying and detecting HAV sequences (Abstract). This reference specifically teaches an embodiment in which HAV and human parvovirus B19 are simultaneously detected in human samples (para. 68). This involves the use of amplification oligomers and detection probes, and both viruses are amplified and detected in the same reaction mixture (para. 68). Carlson concludes that “These results show that HAV nucleic acid is specifically detected when the sample includes HAV and another virus, human parvovirus B19, which is also specifically detected,” (para. 68).
However, Carlson does not teach the recited sequences in claim 33.
Pichuantes teaches primers and probes for HAV (Abstract). This reference specifically teaches SEQ ID NO: 29, which is an insert encoding the full length HAV open reading frame (Figure 3 and column 3, para. 5). SEQ ID NO: 29 includes instant SEQ ID NOs: 173 and 174. In addition, Pichuantes teaches that, “Sequence [sic] of polynucleotides that encode HAV proteins are also useful for designing primers for polymerase chain reaction (PCR),” (column 14, para. 3), and that PCR products can be detected using quantitative methods, such as by measuring fluorescence (column 17, para. 3).
However, this reference does not teach instant SEQ ID NOs: 175 and 177.
Zhang teaches the complete HAV genome (English Translation para. 1). This genome can be found in SEQ ID NO: 1, and it contains instant SEQ ID NOs: 175 and 177. Zhang also teaches that primers can be made from SEQ ID NO: 1 for use in detecting HAV, and that these primers can be between 15-100 nucleotides in length (English Translation paras. 16-17). These primers can then be used for PCR (English Translation para. 27).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to use the teachings of Carlson, Pichuantes, and Zhang to add to the method of Lee in view of Yu and arrive at the methods of instant claims 33 and 39. This would involve including primers for HAV in the amplification methods described by Lee in order to detect parvovirus and HAV in a single sample. Carlson provides evidence that these viruses can specifically be detected separately in a single mixture, and by developing such a multiplex assay, it would allow for more efficient diagnostic tools and would save on diagnostic reagents and equipment. Carlson also provides a reasonable expectation of success, as they accomplished a successful multiplex assay with these two viruses. As for the primer sequences, as stated above, Yu teaches designing multiple primers from known sequences, and so this would motivate one of ordinary skill in the art to design HAV primer sequences for use in the method of Lee, in view of Yu, and in view of Carlson. Thus, the ordinary artisan would have been motivated to use the commercially available software disclosed in Yu and the known HAV sequences disclosed by Pichuantes and Zhang to design additional primers for use in the method and oligonucleotide combination of Lee, in view of Yu, and in view of Carlson, and in the absence of unexpected results, the claimed primers (instant SEQ ID NOs: 173-175 and 177) simply represent the result of an obvious series of steps.
Therefore, claims 33 and 39 are prima facie obvious over Lee, in view of Yu, and further in view of Carlson, in view of Pichuantes, and in view of Zhang.
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 21, 28, 33, 36, 38 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9, and 23-26 of U.S. Patent No. 9,752,201 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of the ‘201 patent recites a method for detecting human parvovirus involving two amplification oligomers, one of SEQ ID NO: 80 (which is identical to instant SEQ ID NO: 80), and one of SEQ ID NO: 111 or 112 with a 5’ promoter attached (which are identical to instant SEQ ID NOs: 111 and 112, also with a 5’ promoter attached). Thus, this claim teaches the oligomer combination of instant claim 21. The method of claim 1 also reads on instant claim 36, as a sample is contacted with the oligomers, in vitro amplification is performed, and the presence/absence of parvovirus is detected. Claim 1 of the ‘201 patent also reads on the oligomer combination of instant claim 38, as in instant claim 38, SEQ ID NO: 80 can be used, as well as SEQ ID NOS: 91 or 92, which are equivalent to SEQ ID NOs: 111 and 112 with the addition of 5’ promoters.
Claim 9 of the ‘201 patent combines the parvovirus detection with HAV detection, where the same first and second amplification oligomers for HAV presented in instant claim 33 are used. This claim also reads on instant claim 39, as in vitro amplification and detection steps are also recited.
Claim 23 of the ‘201 patent recites the additional use of SEQ ID NO: 119, and so reads on instant claim 28.
Claim 24 of the ‘201 patent recites the use of a T7 promoter sequence for the second amplification oligomer. As this type of promoter is the one used in the instant claims (see Table 3 of the instant specification), this claim also reads on instant claims 21, 36, and 38.
Claim 25 recites the use of a particular promoter sequence (5’-aatttaatac gactcactat agggaga-3’). This corresponds to the same promoter used in the sequences of the instant claims that contain a promoter sequence (see para. 47 above), and so this claim also reads on instant claims 21, 36, and 38.
Claim 26 requires the specific use of SEQ ID NOs: 91 and 92 as the second amplification oligomer, and so even more explicitly reads on the limitations of instant claims 21, 36, and 38.
Conclusion
No claims are currently allowable.
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/F.F.G./Examiner, Art Unit 1681
/ANGELA M. BERTAGNA/Primary Examiner, Art Unit 1681