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 .
Election/Restrictions
2. Applicant’s election without traverse of the following species for examination in the reply filed on June 8, 2026 is acknowledged: protease as the first enzyme and a nucleic acid processing enzyme as the second enzyme.
As noted by Applicant in the response, all of the pending claims (i.e., claims 1, 4, 6-10, 12-18, 20, 22-24, 26, and 28 read on the elected species.
Information Disclosure Statement
3. Applicant’s submission of an Information Disclosure Statement (IDS) on the following dates is acknowledged: July 11, 2023; October 2, 2023; January 4, 2024; and April 1, 2024.
All of the cited references have been considered. In the IDS of July 11, 2023, some foreign patent documents are annotated “abstract only” because a full copy of the reference was not submitted.
Specification
4. The specification is objected to because it fails to provide clear support for all of the options recited in claim 9. In particular, the specification fails to provide clear support for nano-partitions with a size between about 3 nm and about 1000 nm or nano-partitions with a size between about 3 nm and about 300 nm as recited in claim 9. It is noted that this is not a new matter issue since the subject matter is recited in the original claims. Therefore, as discussed in MPEP 2163.06 III, Applicant may amend the specification to provide the required support without introducing new matter.
Drawings
5. The drawings filed on May 12, 2023 are objected to for three reasons.
First, Figures 13B and 13C contain oligonucleotide sequences that require a sequence identifier per 37 CFR 1.821(a), but no sequence identifiers are present in the figures or the “Brief Description of the Drawings” section. As noted in MPEP 2422.02, when the figures include nucleic acid sequences that fall within the definition set forth in 37 CFR 1.821(a), said sequences must be identified with a sequence identifier, either in the figure or the “Brief Description of the Drawings” section. See also 37 CFR 1.821(d).
Second, the drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they do not include the following reference sign(s) mentioned in the description: 1190.
It is acknowledged that the specification states that this reference character is not shown in the drawings (page 57, para. 216), but 37 CFR 1.84(p)(5) does not appear to allow for this since the rule states that “Reference characters mentioned in the description must appear in the drawings.” Deleting reference character 1190 from the specification would address the issue.
Alternatively, if Applicant chooses not to amend the specification to delete reference character 1190, corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Third, the drawings are also objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: 508, 510, 512, 516, 518, 608, 610, 612, 616, 1301, and 1302.
It is acknowledged that for the reference characters in Figures 5 and 6 (i.e., all of the above reference characters except for 1301 and 1302) that the specification states that these reference characters correspond to the analogous structures in Figure 4 (pages 38-39, paras. 154-155), but 37 CFR 1.84(p)(5) does not appear to allow for this since the rule states that “Reference characters not mentioned in the description shall not appear in the drawings.”
Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
6. REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”. More specifically, Figures 13B and 13C contain nucleic acid sequences that fall within the definition set forth in 37 CFR 1.821(a), but a Sequence Listing has not been filed.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. The sequences appear in Figures 13B and 13C.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Interpretation
7. The specification includes explicit (i.e., limiting) definitions for certain terms used in the claims.
One such term is “nano-partition,” which is defined as having “dimensions on the order of about 3 nm (or 0.003 mm) to about 10 mm (or 10,000 nm) and are made of porous materials that allow small molecules (e.g., water, buffer salts, NTPs, inhibitors) but not enzymes, proteins, or other large macromolecules, to pass through” (page 12, para. 84).
Another such term is “partition,” which is defined as “a space or volume that is suitable to contain one or more species or conduct one or more reactions” (page 12, para. 82). Examples of “a partition” disclosed in the specification include droplets and wells (para. 82).
Claim Objections
8. Claim 23 is objected to because a conjunction is missing before the last option for the un-fixing agent.
Claim Rejections - 35 USC § 112
9. 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.
Claim 15 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 15 contains the following trademarks/trade names: ALCALASE, BIOPRASE, ARCTICZYMES, ESPERASE, GENENASE, KAZUSASE, MAXATASE, SAVINASE, AND THERMOASE. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe particular proteases and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 112
10. 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.
Claim 9 is 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.
Claim 9 depends from claim 1 and states that the nano-partition has a size of between about 3 nm and about 10,000 nm, between about 3 nm and about 1,000 nm and between about 3 nm and about 300 nm. This claim is rejected under 35 U.S.C. 112(d) because not all of the options for the nano-partition size are further limiting. As noted above, the explicit definition for “nano-partition” in para. 84 of the specification of the instant application requires a nano-partition to have “dimensions on the order of about 3 nm (or 0.003 mm) to about 10 mm (or 10,000 nm).” Therefore, the first option in claim 9 is not further limiting because it is already required by claim 1.
Applicant may cancel the claim, amend the claim to place it in proper dependent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 103
11. 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.
12. 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.
13. Claims 1, 4, 6-10, 12-18, 20, 24, 26, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Saul et al. (WO 2011/002319 A2) in view of Hindson et al. (US 2014/0227684 A1).
The instant claims are drawn to a method that comprises using a first enzyme to catalyze a reaction with a biological sample and a second enzyme to catalyze a reaction with the biological sample or a component thereof. A nano-partition is used to separate the first and second enzyme such that they cannot interact with one another. As noted above, Applicant has elected “protease” as the species of first enzyme for examination and “nucleic acid processing enzyme” as the species of second enzyme for examination.
Saul discloses a method that combines deactivation of contaminating nucleic acids in a sample, extraction of target nucleic acids, and amplification and detection of the extracted target nucleic acids in a single reaction vessel (see, e.g., the abstract and paras. 12-13).
Regarding claims 1, 13, 15, and 16, the method of Saul comprises the following steps (see, e.g., para. 13):
(a) providing a partition (i.e., the vessel or tube) containing a biological sample, a first enzyme (i.e., the thermophilic proteinase), and a second enzyme (i.e., the amplification reagent, which may include a polymerase and/or reverse transcriptase per paras. 92-93), wherein the first and second enzymes catalyze different reactions, and wherein the second enzyme is encapsulated in a heat-labile microcapsule to prevent it from interacting with the first enzyme (see paras. 27, 47, and 122-123);
(b) using the first enzyme to catalyze a reaction with the biological sample (para. 13, where the proteinase is used to digest proteins in the sample; see also paras. 78-84 for additional description of the proteinase digestion step); and
(c) using the second enzyme to catalyze a reaction with a component of the biological sample (para. 13, where the amplification is taught; see also paras. 91-104 for additional description of the amplification step),
wherein (c) occurs after (b) (para. 13; see also paras. 47-48 and paras. 122-123).
Regarding claim 4, in the method of Saul, reaction of the second enzyme (i.e., polymerase and/or reverse transcriptase) with the biological sample generates analytes (amplification products) (para. 13; see also paras. 91-104). Saul further teaches detecting the amplification products (para. 22; see also paras. 102 and 108-116).
Regarding claim 6, in the method of Saul, the first enzyme (proteinase) digests proteins in the biological sample that, including nucleases (paras. 13 and 80-82). Therefore, reaction of the first enzyme with the biological sample generates a substrate for the second enzyme (polymerase or reverse transcriptase) by rendering the substrate accessible to the second enzyme.
Regarding claim 7, Saul teaches that the first and second enzymes may be incompatible since the first enzyme (proteinase) may degrade the second enzyme (DNA polymerase) (see, e.g., para. 122).
Regarding claims 8 and 18, Saul teaches that the partition (i.e., vessel or tube) may contain additional assay reagents (see, e.g., paras. 13 and 60-70, where nucleic acid deactivating reagents are taught; see also paras. 27, 91-99, 122, and 123, where Saul teaches that the capsules may contain amplification reagents in addition to a polymerase or reverse transcriptase). Further regarding claim 18, by teaching that the amplification reagents may include reverse transcriptase, Saul also suggests cDNA synthesis reagents (e.g., NTPs and primers).
Regarding claim 15, as noted above, Saul teaches that the first enzyme is a protease (para. 13). Saul further teaches that the protease may be an alkaline proteinase (para. 81).
Regarding claim 20, Saul teaches that the biological sample may be derived from a tissue sample, a biopsy, or a blood sample (paras. 29 and 74).
Regarding claim 24, Saul teaches that the microcapsule is degradable by heat and that the method may include applying heat to degrade the microcapsule (paras. 27 and 122-123).
Regarding claim 28, Saul teaches that the method further comprises deactivating the first enzyme (proteinase) (para 13; see also paras. 78-80).
Saul is not anticipatory because the reference does not disclose the size of the microcapsules used to encapsulate the nucleic acid processing enzyme (i.e., the polymerase and/or reverse transcriptase in the amplification reaction). As noted above, a “nano-partition” is required by the explicit definition in para. 84 of the specification of the instant application to have “dimensions on the order of about 3 nm (or 0.003 mm) to about 10 mm (or 10,000 nm) and are made of porous materials that allow small molecules (e.g., water, buffer salts, NTPs, inhibitors) but not enzymes, proteins, or other large macromolecules, to pass through.” Since Saul is silent as to the microcapsule size used to encapsulate the polymerase and/or reverse transcriptase, the reference fails to anticipate the method of independent claim 1.
As a result, Saul also fails to meet the requirements of dependent claims 9, 10, and 12, which further limit the nano-partition recited in independent claim 1. Saul also does not teach that the microcapsule comprises one of the materials recited in dependent claim 14.
Hindson, though, discloses methods for processing nucleic acids that include the use of encapsulated reagents (e.g., polymerase and/or reverse transcriptase), wherein the reagents may be encapsulated in a capsule or a droplet that is selectively activated via a stimulus (e.g., heat, light, or a chemical reaction as recited in claim 24) to release the enzyme(s), thus controlling when the enzyme(s) is/are able to act (abstract and paras. 3-6, 12, 18-20, and 25). As noted in paras. 206-207 of Hindson, the encapsulated reagents may be used in an amplification method. As well, Hindson teaches that the capsules may have a mean diameter of 1-250 microns, 1-100 microns, or 1-50 microns (paras. 13 and 26) and may have a mean volume ranging from 1 picoliter or 1 microliter (paras. 14 and 27). These capsule sizes overlap with the required size of about 3 nm to about 10 micrometers, which is also recited in claim 9. Hindson additionally discloses specific examples of capsules with a diameter within the range recited in claim 9 (para. 164). Still further, Hindson teaches that the capsules may have pores that retain a desired species (e.g., a target nucleic acid) but allow transport of smaller molecules (paras. 75 and 251) in addition to teaching that, if desired, a stimulus may be applied to some capsules to create nanopores or an increase in porosity that allows for the release of their contents (paras. 220-221, 224, and 231-232). Lastly, Hindson teaches that the capsules may comprise a hydrogel as recited in claim 14 (paras. 11, 24, and 228). Thus, Hindson discloses capsules that meet the requirements of a nano-partition as defined in the specification of instant application and as recited in claims 1, 9, 14, and 24.
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious to practice the method of Saul using a microcapsule that meets the requirements of a “nano-partition” as defined in the instant application. As discussed above, Hindson discloses methods that are similar to the method of Saul in that they use encapsulated reagents in methods for processing nucleic acids that may include amplification. The ordinary artisan would have recognized from the similarity of the two methods that the capsules of Hindson would be suitable for use in the methods of Saul, and accordingly, would have been motivated to substitute the microcapsules of Saul with those of Hindson with a reasonable expectation of success. See also MPEP 2144.06 and 2144.07, which respectively state that, in the absence of unexpected results, it is prima facie obvious to substitute art-recognized equivalents known to be useful for the same purpose or to select a known material based on its suitability for the intended purpose. In this case, the capsules of Hindson would have been recognized by the ordinary artisan as suitable for use in the method of Saul since they were also used to encapsulate nucleic acid amplification reagents (see, e.g., paras. 3-6, 12, 18-20, 25, and 206-207). As well, no evidence of unexpected results has been presented. Thus, the methods of claims 1, 4, 6-9, 13-16, 18, 20, 24, and 28 are prima facie obvious over Saul in view of Hindson.
Further regarding claims 10 and 12, it also would have been prima facie obvious for the ordinary artisan practicing the method suggested by Saul in view of Hindson to design the nano-partitions such that the pores were any desired size (e.g., one of the sizes recited in claim 10 or capable of allowing the diffusion of mRNA molecules as recited in claim 12). The ordinary artisan would have recognized from the teachings of Saul and Hindson cited above that the porosity/pore size of the capsules (i.e., nano-partitions) was a results-effective variable that should be optimized depending on the particulars of the assay. Accordingly, the ordinary artisan would have been motivated to select any desired size for the pores in the nano-partitions and would have had a reasonable expectation of success in view of the guidance in Saul and Hindson concerning pores in capsules to be used in nucleic acid analysis methods. Thus, the methods of claims 10 and 12 are also prima facie obvious.
Further regarding claim 17, it also would have been prima facie obvious to practice the method suggested by Saul in view of Hindson in a plurality of discrete droplets. Saul provides motivation to reduce the reaction volume of individual reactions by teaching that the method can be performed in a microfluidic devices or on a microchip (para. 30). Then, since the teachings of Hindson indicate that a large number of reactions can be conducted in parallel in discrete droplets (paras. 37-48, 125, and 129-130), the ordinary artisan would have been motivated to adapt the method of Saul to be conducted in droplets to obtain this benefit and would have had a reasonable expectation of success in view of the extensive guidance throughout Hindson as to the use of capsules within large pluralities of discrete droplets to conduct reactions (see, e.g., paras. 4-17, 37-48, 55-59, 125, and 129-130; see also Figs. 1A-1B, 8A-8B, 13A-13E, and 15A-15B and their accompanying description in Hindson). Thus, the method of claim 17 is also prima facie obvious.
Further regarding claim 26, Saul teaches using heat to degrade the microcapsules and release their contents (paras. 27 and 122-123). Saul also teaches using heat to deactivate the first enzyme (proteinase) (paras. 78-80). Saul does not clearly teach that the heating step used to degrade the microcapsules also deactivates the first enzyme (proteinase), but this would have been an obvious modification since the ordinary artisan would have recognized that a heating step that both deactivates the proteinase and degrades the microcapsules would be more efficient. The ordinary artisan would have had a reasonable expectation of success since Saul provides guidance as to what conditions are necessary to degrade the proteinase (paras. 78-80), and each of Saul and Hindson provide guidance as to the use of heat to degrade a heat-labile capsule (paras. 27 and 122-123 of Saul; paras. 25, 218, and 227-229 of Hindson). Thus, the method of claim 26 is also prima facie obvious.
To summarize, the methods of claims 1, 4, 6-10, 12-18, 20, 24, 26, and 28 are prima facie obvious over Saul in view of Hindson.
13. Claims 22 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Saul et al. (WO 2011/002319 A2) in view of Hindson et al. (US 2014/0227684 A1) and further in view of Kool et al. (US 2017/0283860 A1; IDS reference).
As discussed above, the teachings of Saul in view of Hindson render obvious the methods of claims 1, 4, 6-10, 12-18, 20, 24, 26, and 28.
Regarding claim 22, Saul teaches that the method can be used with a wide variety of biological samples (paras. 29 and 74-77), but the reference does not teach using a fixed biological sample. As a result, Saul fails to disclose inclusion of an un-fixing agent in the partition as required by claim 23. Hindson does not remedy these deficiencies in Saul because although the reference teaches the use of a fixed tissue sample (para. 175), the fixed sample is never placed in a partition together with a capsule.
Prior to the effective filing date of the claimed invention, though, it would have been prima facie obvious to use a fixed sample as the biological sample when practicing the method suggested by Saul in view of Hindson. Saul provides motivation to use any sample known to contain nucleic acids useful for analysis by teaching that the disclosed method can be used with a wide variety of samples (paras. 29 and 74-77). Hindson and Kool each provide motivation to use a fixed sample since their teachings indicate that such samples contain nucleic acids that may be desirable to analyze (Hindson at para. 175; Kool at paras. 3-4). Then, since Kool described how to use an “un-fixing” agent to facilitate analysis of the nucleic acids in the fixed tissue sample (paras. 5-9, 35-36, and 64-84), the ordinary artisan would have been motivated to further include an un-fixing agent as taught by Kool in Table 1 in the partitions (i.e., reaction tubes or vessels) of Saul when practicing the method suggested by Saul in view of Hindson, recognizing that this would be necessary for analysis of this type of sample.1 The ordinary artisan would have had a reasonable expectation of success in view of the guidance throughout Kool concerning un-fixing agents and also since Kool taught that PCR could be used to analyze nucleic acids released from the fixed sample (see, e.g., paras. 9 and 71). Thus, the methods of claims 22 and 23 are prima facie obvious.
Conclusion
14. No claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Angela Bertagna whose telephone number is (571)272-8291. The examiner can normally be reached 8-5, M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANGELA M. BERTAGNA/Primary Examiner, Art Unit 1681
1 It is noted that Table 1 of Kool includes compound (4) in the instant claim 23.
Prosecution Insights