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 .
Continued Examination Under 37 CFR 1.114
2. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 19 February 2026 has been entered.
3. Applicant's arguments and amendments to the claims presented in the reply of 19 February 2026 have been fully considered but do not place the application in condition for allowance. All rejections not reiterated herein are hereby withdrawn. In particular, the previous rejection of claims 1, 2, 16 and 22 under 35 U.S.C. 101 have been obviated by the amendments to the claims to recite that the kits, compositions and reaction mixtures comprise an RSV B probe molecule species of about 26 to 100 nucleotides in length wherein the probe molecule species comprises the nucleotide sequence of the elected SEQ ID NO: 102 (or one of the non-elected sequences of SEQ ID NOs: 102 and 107-111 and 113-114) and comprises a chemiluminescent moiety, a fluorophore moiety, a quencher moiety, and both a fluorophore moiety and a quencher moiety. The recited probe is not a product of nature. The probe constitutes a patent-eligible element that adds something significantly more to the recited judicial exception.
Claim Status
4. Claims 1-4, 7-8, and 11-22 are pending.
Claims 11, 12, 14 and 15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 8 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1-4, 7, 13 and 16-22 read on the elected invention and have been examined herein. The claims have been examined only to the extent that they read on the elected species of the first RSV primer of SEQ ID NO: 100, the second RSV primer of SEQ ID NO: 115 and the RSV probe of SEQ ID NO: 102 The claims encompass non-elected species of primers and probes. Prior to the allowance of claims, any non-elected subject matter which has not been rejoined with the elected subject matter will be required to be removed from the claims.
Modified Claim Rejections - 35 USC § 103
5. 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 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.
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.
Claim(s) 1, 3, 7, 13, 16, 17, and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (U.S. 20090181360) in view of NCBI Database (GenBank Accession No. AF013254, 30 September 1999, National Library of Medicine, NIH, available via URL: <ncbi.nlm.nih.gov/nuccore/AF013254>), and Sigma-Aldrich (qPCR Technical Guide. 2008 Available via url: <gene-quantification.com/SIAL-qPCR-Technical-Guide.pdf>).
Chen teaches methods, compositions and kits for detecting human RSV B, as well as human RSV A, and influenza A and influenza B (e.g., para [0060]).
Chen teaches primers for amplifying human RSV B Matrix gene (M gene) sequences and probes for detecting the amplified sequences, wherein the primers and probes comprise Matrix (M) gene sequences from the Human Respiratory Syncytial Virus B nucleotide sequence provided at GenBank Accession No. AF013254 (SEQ ID NO:11 therein; see, e.g., para [0036-0038], [0042], [0058] and [0060]).
Chen exemplifies primers for specifically amplifying RSV B Matrix (M) gene sequences wherein the primers consist of SEQ ID NO: 25, 26, or 27 therein, and a probe for detecting the amplified RSV B sequences wherein the probe consists of SEQ ID NO: 28 therein (e.g., para [0042] and Table 1). See also Table 2 which provides the location of primer and probe sequences complementary to the M gene for amplifying and detecting RSV B in GenBank Accession No. AF013254, as well as GenBank Accession No. NC_001781, AY353550.
Chen teaches that the probes are labeled with a fluorescent moiety or both a fluorescent moiety and quencher (e.g., para [0030-0032] and [0042]).
Chen does not teach kits, compositions or reaction mixtures comprising the presently claimed forward RSV B primer of SEQ ID NO: 100 and the reverse RSV B primer of SEQ ID NO: 115, alone or in combination with the RSV B probe of SEQ ID NO: 102.
However, Chen teaches that additional primers and probes can be readily prepared for amplifying and detecting RSV B (e.g., para [0121]).
Chen provides guidance for the selection of additional RSV B primers and probes, and particularly states:
[0074] The skilled artisan is capable of designing and preparing primers that are appropriate for amplifying a target sequence in view of this disclosure. The length of the amplification primers for use in the present invention depends on several factors including the nucleotide sequence identity and the temperature at which these nucleic acids are hybridized or used during in vitro nucleic acid amplification. The considerations necessary to determine a preferred length for an amplification primer of a particular sequence identity are well known to the person of ordinary skill in the art.
[0075] Primers that amplify a nucleic acid molecule can be designed using, for example, a computer program such as OLIGO (Molecular Biology Insights, Inc., Cascade, Colo.). Important features when designing oligonucleotides to be used as amplification primers include, but are not limited to, an appropriate size amplification product to facilitate detection (e.g., by electrophoresis or real-time PCR), similar melting temperatures for the members of a pair of primers, and the length of each primer (i.e., the primers need to be long enough to anneal with sequence-specificity and to initiate synthesis but not so long that fidelity is reduced during oligonucleotide synthesis). Typically, oligonucleotide primers are 15 to 40 nucleotides in length.
[0076] Designing oligonucleotides to be used as hybridization probes can be performed in a manner similar to the design of primers. As with oligonucleotide primers, oligonucleotide probes usually have similar melting temperatures, and the length of each probe must be sufficient for sequence-specific hybridization to occur but not so long that fidelity is reduced during synthesis. Oligonucleotide probes are generally 15 to 60 nucleotides in length.
Chen teaches that the sequence of the gene encoding for the RSV B matrix protein was well known in the prior art and Chen specifically exemplifies designing primers to the gene encoding the matrix protein present within GenBank Accession No. AF013254. Each of present SEQ ID NO: 100, 115 and 102 are present within the sequence of GenBank Accession No. AF013254, as shown in the alignments below, wherein “Query” is the sequence of GenBank Accession No. AF013254 and “Sbjct” is the sequence of one of the present primers and probes:
SEQ ID NO: 100:
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Note that present SEQ ID NO: 100 includes a Y at position 12 and thereby includes either a “T” (as present in AF013254) or a C.
SEQ ID NO: 115:
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SEQ ID NO: 102:
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Moreover, the prior art provides extensive guidance, direction and motivation to select primers to amplify target nucleic acids and probes to detect amplified nucleic acids.
For example, Sigma-Aldrich provides a review of the parameters which effect PCR sensitivity and specificity and discloses the parameters for the design of optimal PCR primer and probe sequences to be used in quantitative RT-PCR (e.g., p. 10). The reference teaches optimizing the primers selected for multiplex reactions in particular, and provides guidance for performing routine assays that may be performed to ensure the optimal design and performance of primers and probes (e.g., p. 17, and p. 25-26). It is further disclosed that software programs are available to assist with primer and probe selection (e.g., p. 11 and 18). Sigma-Aldrich also teaches using primers and probes to detect viruses in clinical samples (e.g., p. 1 p. 7, col. 2; p. 8, col. 1). For instance, it is stated that “For instance, qPCR can be used to measure viral load or bacterial pathogens in a clinical sample, to verify microarray data, for allelic discrimination or to determine RNA (via cDNA) copy numbers.”
Designing primers and probes to amplify and detect specific target nucleic acids identified in the prior art (including reverse complements), which are equivalents to those taught in the art was well-known in the prior art, as exemplified by the teachings of Chen, and requires only routine experimentation. The prior art teaches the parameters and objectives involved in the selection of oligonucleotides that function as primers and probes (see Sigma-Aldrich and Chen). The prior art is replete with guidance and information necessary to permit the ordinary artisan in the field of nucleic acid detection to design primers and probes to sequences identified in the prior art. As discussed above, the ordinary artisan would have been motivated to have designed and tested new primers and probes that function to amplify and detect RSV B in view of the teachings of Chen.
For the reasons provided above, the ordinary artisan would have been motivated to have designed additional primers and probes and would have had more than a reasonable expectation of success of designing additional primers and probes for RSV B, including primers comprising or consisting of present SEQ ID NO: 100 and 115 and the probe of SEQ ID NO: 102.
Further, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have included the primers of SEQ ID NO: 100 and 115 and the probe of SEQ ID NO: 102 in a reaction mixture, composition or kit for the advantage that the primers and probe could be used in combination in amplification reactions to assay for RSV B nucleic acids in test samples.
Regarding the limitation that the probe is about 26 to about 100 contiguous nucleotides in length, Chen teaches that the probes can be up to 60 nucleotides in length (e.g., para [0076]).
Regarding claim 7, Chen teaches that the primers can be peptide nucleic acid primers, locked nucleic acid primers, or phosphorothioate modified primers (e.g., para [0029]) and thereby the primers can include a nucleotide analogue.
Regarding claim 13, the use of the modified compositions of Chen as set forth above in an amplification assay in which a target RSV B nucleic acids were present would have resulted in a composition comprising a first RSV B primer comprising SEQ ID NO: 100, a second RSV B primer comprising SEQ ID NO: 115, an RSV B probe comprising SEQ ID NO: 102, and an amplicon comprising RSV B sequences amplified by the first and second RSV B primers.
Regarding claim 22, Chen further teaches that the reaction mixtures containing the primers also contain reagents for performing the amplification assays, including DNA polymerase and dNTPs (e.g., para [0082] and [0126], and [0127] / Table 3).
6. Claims 2 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (U.S. 20090181360) in view of NCBI Database GenBank Accession No. AF013254, (30 September 1999, National Library of Medicine, NIH, available via URL: <ncbi.nlm.nih.gov/nuccore/AF013254>), and Sigma-Aldrich (qPCR Technical Guide. 2008 Available via url: <gene-quantification.com/SIAL-qPCR-Technical-Guide.pdf>), and further in view of Mullis et al (U.S. Patent No. 4,683,202).
The teachings of Chen, NCBI Database GenBank Accession No. AF013254 and Sigma-Aldrich are presented above.
The combined references do not teach that the primers include a sequence that is not complementary to the RSV B target nucleic acid.
However, Mullis teaches methods for amplifying target nucleic acids. It is stated that:
“In addition, the primer can contain as part of its sequence a non-complementary sequence provided that a sufficient amount of the primer contains a sequence which is complementary to the strand to be amplified. For example, a nucleotide sequence which is not complementary to the template sequence (such as, e.g., a promoter, linker, coding sequence, etc.) may be attached at the 5' end of one or both of the primers, and thereby appended to the product of the amplification process. After the extension primer is added, sufficient cycles are run to achieve the desired amount of new template containing the non-complementary nucleotide insert.” (col. 13, lines 27-41).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the kits of Chen so as to have included in the primers a 5’ / upstream sequence that is not complementary to the target RSV B nucleic acids so that the non-target sequence would be included in the amplification products, such that the additional 5’ / upstream sequence could be used to clone detected amplification products or otherwise modify the amplification products for further processing.
7. Claim(s) 18 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (U.S. 20090181360) in view of NCBI Database (GenBank Accession No. AF013254, 30 September 1999, National Library of Medicine, NIH, available via URL: <ncbi.nlm.nih.gov/nuccore/AF013254>), and Sigma-Aldrich (qPCR Technical Guide. 2008 Available via url: <gene-quantification.com/SIAL-qPCR-Technical-Guide.pdf>), and further in view of Thermo Fisher Scientific (“Thermo Scientific Modified Nucleoside Phosphoramidites,” 2007. 2 pages, available via URL: <assets.thermofisher.com/TFS-Assets/LSG/brochures/Modified-Nucleoside-Phosphoramidites.pdf>) and Shafer, D. (U.S. 20040053275).
The teachings of Chen, NCBI Database GenBank Accession No. AF013254 and Sigma-Aldrich are presented above.
In particular, Chen teaches that the primers can be phosphorothioate modified primers (e.g., para [0029]), and thereby the primers may include nucleotide analogues. Chen does not teach that the primers or the primers and probes each include the nucleotide analogue of 5-me-dC.
However, Thermo Fisher Scientific teaches oligonucleotides for use as probes or primers that incorporate 5-Methyl dC (i.e., 5-Me-dC; see p. 1). It is disclosed that the stability and melting temperature of oligonucleotide duplexes can be improved by the incorporation of 5-Methyl dC into oligonucleotide primers and probes (p. 1).
Further, Shafer (para [0216]) teaches that incorporation of 5-Me-dC into oligonucleotides “can significantly raise melt temperature (Tm) by several degrees, and can diminish non-specific binding of these components.”
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the primers and probes of Chen so as to have incorporated the nucleotide analog of 5-Methyl dC into the primers and probes in order to have increased the melting temperature of the primers and probes and the stability of duplexes formed with the primers and probes, thereby improving the specificity of binding of the primers and probes in amplification and detection assays.
10. Claims 20 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (U.S. 20090181360) in view of NCBI Database (GenBank Accession No. AF013254, 30 September 1999, National Library of Medicine, NIH, available via URL: <ncbi.nlm.nih.gov/nuccore/AF013254>)and Sigma-Aldrich (qPCR Technical Guide. 2008 Available via url: <gene-quantification.com/SIAL-qPCR-Technical-Guide.pdf>), and further in view of Shen et al (U.S. Patent No. 5834254).
The teachings of Chen, NCBI Database GenBank Accession No. AF013254 and Sigma-Aldrich are presented above.
The combined references do not teach that one or more of the primers or probes are in a lyophilized form and that the kit includes a salt as a rehydration reagent.
However, Shen teaches providing the reagents used to perform amplification assays in lyophilized form, including the reagents of primers and reverse transcriptase (e.g., Example 6 at col. 21 lines 1-26). Shen (col. 7, lines 31-55) discloses:
“the present invention comprises a component of a kit for the amplification and specific identification of nucleic acids belonging to one or more phylogenetic groupings of organisms, for example for the specific detection of one or more species within a genus or one or more genera within a family. The invention provides a reconstitutable dried formulation comprising a reverse transcriptase, an RNA polymerase, ribonucleotide triphosphates, deoxyribonucleotide triphosphates, zinc and/or magnesium salts, and a reducing agent in a single container. Amplification primers and an aqueous reconstitution solution may be supplied as one or more additional separate components of the kit. Alternatively, amplification primers may be comprised in the dried formulation. Target sequence-specific nucleic acid hybridization assay probes and any desired unlabeled helper oligonucleotides may be included in the dried formulation or provided in a separate reagent. Upon reconstitution of the dried formulation and addition of the oligonucleotide primers (if not already present), the mixture is contacted with a partially or wholly single-stranded target nucleic acid. If the target nucleic acid has nucleotide sequences complementary to the primer(s) (or the primer portion of a promoter-primer(s)), the reaction will proceed upon incubation of the reaction mixture at a temperature sufficient for nucleic acid amplification.”
Shen (col. 3, lines 41-59) further states:
“A method of storing and shipping reverse transcriptase and RNA polymerase without the need for refrigeration would obviate the necessity for refrigerated transport and/or methods of cold storage such as dry ice, wet packs, dry packs, or styrofoam shipping containers. Such methods would also be more cost effective, since the production overhead associated with these methods of maintaining enzyme activity would be unnecessary. Methods of storing enzymes which would allow the enzyme preparation to tolerate a limited exposure to higher temperatures would eliminate the losses in enzyme activity which could result if the enzyme preparation sits on a loading dock or in a truck during shipment. Such a method would have to be highly reproducible. Moreover, if the enzymes could be provided in a single container in a form compatible with their intended use (such as in a formulation containing all or most of any necessary co-factors and substrates) such a preparation would be more economical to manufacture and more convenient to use.”
Shen teaches that the reconstitution buffer comprises MgCl2 (e.g., col. 10, lines 9-15).
In view of the teachings of Shen, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the kits of Chen so as to have provided one or more of the primers or probe, in a lyophilized form in the kit, as well as to have included the salt of magnesium chloride for rehydrating the amplification reagents. One would have been motivated to have done so to achieve the advantages set forth by Shen of providing an economical and convenient means for performing amplification reactions, and obviating the need for refrigerated transport and cold storage of the amplification reagents.Response to remarks regarding the rejections under 35 U.S.C. 103:
In the reply of 19 February 2026, Applicant traversed the rejections under 35 U.S.C. 103.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Note that the rejections are based on what the references, when considered in combination would have suggested to one of ordinary skill in the art and not what the individual references teach in isolation.
The response argues that the Sigma-Aldrich reference does not provide “guidance for selecting Applicant's claimed primers from GenBank AF013254.” Applicant goes on to critique Sigma-Aldrich as only teaching how to avoid self-complementarity and optimizing reaction conditions. It is argued that “The guidance provided by Sigma-Aldrich might be useful in optimizing previously selected sequences for used in a multiplex assay, but none of the suggestions provided by Sigma-Aldrich provides any direction on selecting primer sequences that will specifically detect multiple species of RSV B without detecting other species and do so in a multiplex assay..”
These arguments have been fully considered but are not persuasive. The rejection is not based on the isolated teachings of Sigma-Aldrich, but on the combination of teachings. When considered as a whole, the prior art teaches the sequences of the RSV B Matrix gene, which sequence includes the sequences of present SEQ ID NO: 100, 115 and 102, suggests generating additional primers and probes to detect the RSV B matrix gene and provides extensive guidance, including well-known software programs for designing primers and probes to known target regions. Accordingly, it is maintained that the ordinary artisan would have been motivated to have designed additional primers and probes and would have had more than a reasonable expectation of success of designing additional primers for RSV B, including primers comprising SEQ ID NO: 100 and 115, as well as probes comprising SEQ ID NO: 102.
Regarding the arguments pertaining to multiplex assays, it is noted that the present claims are not drawn to multiplex assays. The claims are drawn to kits, compositions and reaction mixtures which detect only RSV B per se. There is no requirement for additional primers and probes that detect multiple strains / species of RSV B in a multiplex reaction / assay.
The response argues “the Examiner has failed to provide any nexus between NCBI Database (Genbank AF013254) and any of the guidance of Chen or Sigma-Aldrich that would lead someone of skill in the art to arrive at the primers as claimed.”
This argument has been fully considered but is not persuasive. The rejection clearly sets forth that Chen teaches generating primers and probes from the RSV B matrix (M) gene sequence (e.g., para [0226-0117] and particularly the Matrix gene sequence of AF013254. For instance, Chen (para [0058]) states “FIG. 11 is nucleotide sequence of the Human Respiratory Syncytial Virus B M gene sequence provided at GenBank Accession No. AF013254 (SEQ ID NO:11).”
Table 2 of Chen also lists the target nucleic acid sequence for designing the RSV B primers and probes including GenBank Accession No. AF013254, as shown below:
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Although Sigma-Aldrich does not specifically teach GenBank Accession No. AF013254, it was not cited for such a teaching. The ordinary artisan would have recognized that Sigma-Aldrich is a general reference that provides guidance for generating primers and probes to target sequences, including viral sequences, and would be applicable to additional nucleotide sequences.
The response states:
“The Examiner states (p. 22 of the office action), "the present claims are drawn to primers "comprising" sequence ID NO: 100 and SEQ ID NO: 115 and a probe "comprising" SEQ ID NO: 102." The Examiner's interpretation is incorrect. With respect to the primers, the claims recite the target hybridizing sequence consists of the nucleic acid sequence of SEQ ID NO:100 and SEQ ID NO:115. Thus, while the claimed primers can have nucleotide sequence in addition to the target hybridizing sequence (e.g., non-target hybridizing sequence) the target hybridizing sequence consists of SEQ ID NO:100 or 115.”
This argument has been fully considered but is not persuasive because the claims recite the language of “comprises a target hybridizing sequence consisting of a nucleic acid sequence.” The recitation of “comprises” prior to consisting of means that additional nucleotides may be present in addition to the “target hybridizing sequence.” The claims do not recite that the additional sequences are limited to “non-target hybridizing sequences.” What constitutes a “target hybridizing sequence” is arbitrary since the target is not defined as limited to consisting of only a specific sequence. The claims do not exclude the presence of additional RSV B sequences flanking SEQ ID NO: 100, 115 and/or 102. This is in contrast to a claim that recites, for example, a primer consisting of: i) a target hybridizing sequence consisting of SEQ ID NO: 100 and ii) a non-target hybridizing sequence that does not hybridize to a RSV B nucleotide sequence.
The response states:
“Applicant has used one such program, Primer3Plus (referenced in Untergasser NAR, 2007, Vol 35, W71-W74), to select detection primers for GenBank AF013254. As shown in Appendix 1, Primer3Plus identified 5 sets of primers (from 141847 possible forward primers and 147072 possible reverse primers) for use in detection of GenBank AF013254. None of the forward or reverse primers identified by Primer3Plus had any overlap with claimed SEQ ID NOs:100-101 and 106 or SEQ ID NO: 115. Two additional programs-Primer-BLAST and Eurofins PCR Primer Design Tool-also failed to identify Applicants claimed primers (see Appendix 1).”
However, Applicant’s arguments pertaining to the software programs and Appendix 1 are not provided in declaratory form. See MPEP 716.01(c):
“I. TO BE OF PROBATIVE VALUE, ANY OBJECTIVE EVIDENCE SHOULD BE SUPPORTED BY ACTUAL PROOF
Objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. See, for example, In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984) (“It is well settled that unexpected results must be established by factual evidence.” “[A]ppellants have not presented any experimental data showing that prior heat-shrinkable articles split. Due to the absence of tests comparing appellant’s heat shrinkable articles with those of the closest prior art, we conclude that appellant’s assertions of unexpected results constitute mere argument.”). See also In re Lindner, 457 F.2d 506, 508, 173 USPQ 356, 358 (CCPA 1972); Ex parte George, 21 USPQ2d 1058 (Bd. Pat. App. & Inter. 1991).
II. ARGUMENTS BY APPLICANT CANNOT TAKE THE PLACE OF EVIDENCE
Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.” (Emphasis added).
The reason for requiring evidence in declaration or affidavit form is to obtain the assurances that any statements or representations made are correct, as provided by 35 U.S.C. 25 and 18 U.S.C. 1001.
Note that this should not be construed as an invitation for providing a declaration or affidavits. See MPEP 716.01 regarding the timeliness of filing declarations/affidavits.
Additionally, the information in Appendix 1 is not clear. Appendix 1 refers to yellow, green and green/yellow alternating sequences (as well as pink and blue sequences at p. 17). However, the information provided is in black and white text. Also, the appendix does not list the specific parameters that were used for the search. Since most of the primers identified are 20 nucleotides in length, it is not clear as to whether the length of the primers was limited to 20 nucleotides. Herein, the RSV B primers of SEQ ID NO: 100 and 115 are 23 nucleotides in length and the RSV probe is 26 nucleotides in length. Also, as discussed above, the claims encompass primers of any length that comprise the 23 nucleotides of SEQ ID NO: 100 or 115. It is not clear from the information provided that the search that was conducted would have fairly identified primers comprising the longer length primers of SEQ ID NO: 100 and 115.
Applicant argues “the Examiner has failed to provide any evidence or reasoning that shows how any of the "well-known" parameters constrains the number of possible primers in a way that would lead the skilled person to the claimed primers.”
This argument has been fully considered but is not persuasive. The claims encompass primers and probes that are fragments of the RSV B matrix gene of GenBank Accession No. AF013254. The prior art teaches generating additional primers and probes to known gene sequences to and provides extensive guidance to generate such additional primers and probes which are equivalents those in the prior art. There is no requirement for the examiner to provide evidence that the combined prior art results in Applicant’s claimed primers. There is only a requirement to establish that the combined prior art when considered as a whole would have both suggested the claimed primers and probes and the ordinary artisan would have had a reasonable expectation of obtaining the claimed primers and probes.
The response states:
“Applicant has provided post-filing data showing the sensitivity and specificity of the RSV B primers and probe as claimed (Appendix 2).
As shown at Table 8, the claimed RSV B primers and probe detected 1 x 1000 TCID50/mL RSV B. Chen is silent with respect to sensitivity. One skilled in the art could not have predicted, and would have had no expectation, that primers having the sequences as claimed would be able to detect 1x 1000 TCID50/mL RSV B. As shown in Tables 9 and 11, the claimed RSV B primers and probes detected 2 different strains of RSV B (Table 9), without detecting numerous other pathogens (Table 11). One skilled in the art could not have predicted, and would have had no expectation, that primers having the sequences as claimed would be able to (a) detect multiple species of RSV B without detecting 52 common respiratory pathogens, and (b) detect RSV B in a multiplex system that also contains primers and probes for detection Flu A and Flu B.”
These arguments and the content of Appendix 2 have been fully considered but are not persuasive. First, Appendix 2 not provided in declaratory form. There are no assurances that any statements or representations made therein are correct, as provided by 35 U.S.C. 25 and 18 U.S.C. 1001.
Secondly, it is not clear as to what primers and probes were used in the assay described in Appendix 2 since the reply refers generally to “RSV B primers and probe as claimed.” With respect to RSV B, there is no clear statement that the primers were limited to nucleic acids consisting of SEQ ID NO: 100 and 115 and the probe was limited to a nucleic acid consisting of SEQ ID NO: 115 (and one of the labels recited in claim 1). If the primers and probes were limited to the sequences consisting of SEQ ID NO: 100, 115 and 102, the results provided therein cannot be extrapolated to the breadth of the claimed primers and probe claimed since the claimed primers and probe are not limited to nucleotide sequences consisting of SEQ ID NO :100, 115 and 102. See above discussion regarding the claim language of “comprises a target hybridizing sequence consisting of a nucleic acid sequence.” The presence of nucleotides of any identity flanking the sequences of SEQ ID NO: 100 and 115, and particularly sequences of any identity present at the 3’ end of the primers of SEQ ID NO: 100 and 115, would be expected to substantially alter the annealing specificity of the primers. There is no showing that primers comprising any number of additional nucleotides 5’ and/or 3’ of SEQ ID NO: 100 and 115 would provide the asserted unexpected improved results obtained with the primer pair consisting of SEQ ID NO: 100 and 115. Note also that claim 1 recites that the “the RSV B probe molecule species is about 26 to about 100 contiguous bases in length, comprises the nucleotide sequence” of SEQ ID NO: 102 and thereby the 5’ and 3’ flanking nucleotide sequences of the probe are not defined. It has not been established that the results obtained with a probe consisting of SEQ ID NO: 102 would be the same as the results obtained with a probe comprising SEQ ID NO: 102 flanked (5’ and/or 3’) by 74 nucleotides of any identity. Accordingly, the results shown in Appendix 2 are not commensurate in scope with the claims.
The rejections under 35 U.S.C. 103 are maintained for the reasons set forth above.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 EST.
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, Wu-Cheng Winston Shen 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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/CARLA J MYERS/Primary Examiner, Art Unit 1682
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