Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of the claims
Applicant’s amendments filed 10/28/2025 is acknowledged. claims 1-3, 5-7, 9-13 and 31-41 are pending and claim 36-41 were previously withdrawn from consideration as being directed to non-elected invention. See the office action of .
Therefore, claims 1-3, 5-7, 9-13 and 31-35 are examined on merits in this office action.
Claim Rejections - 35 USC § 103
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 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 1-3, 5-7 and 9-13 and 31-35 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kool et al (US 2017/0283860A1) in view of Jonas et al (WO2016162309A1).
In regards to claims 1, 32, 34 and 35, Kool discloses method of de-crosslinking a formalin fixed tissue by contacting the fixed biological tissue with an adduct reversal agent (abstract), thereby de-crosslinking the fixed biological tissue (Abstract and Claim 1). Kool teaches that the adduct reversal agent is a compound selected from Table 1 (abstract and claim 9), which table 1 (page 11) discloses 2-aminobenzoic acid (
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) for adduct reversal. The compound 2-aminobenzoic acid reads on the formula (I) of claims 1, 34 and 35 with the following selection: A is C(=O)OH, each of X1, X2, X3 and X4 is CH. Note that claim 35 does not further limit claim 34 limitation to at least one of the X1, X2, X3 or X4 to CRa but merely defines Ra.
Kool teaches that biological sample is a tissue sample that has been embedded in a convenient media, which includes but are not limited to: paraffin, paraffin-containing compounds, araldite, celloidin, DURCUPAN™. Kool teaches that the fixed specimens have been fixed with a variety of cross-linking agents, such as formaldehyde, paraformaldehyde, glutaraldehyde, or 1-ethyl-3-(3-dimethylaminopropyl) (paragraph [0064]). Kool teaches that the adduct reversal agent can catalyze the removal of adducts and/or crosslinks under relatively mild conditions (conditions that are not as damaging to biological samples, such as tissue samples, as the conditions used by other methods of crosslink removal). Thus, the subject methods result in less damage to biomolecules than other available methods for removing adducts and/or crosslinks. For example, the subject methods can result in much less damage to biomolecules than other available methods for removing adducts and/or crosslinks. Other methods use high temperatures and are carried out at pHs that are damaging to biomolecules such as nucleic acids and proteins. Thus, biomolecules can be “recovered” intact from aldehyde fixed samples using the subject methods. Because the subject methods can be carried out in relatively mild conditions (pH near neutral, temperatures near room temperature, short time frame of treatment, etc.), and inflict less damage on biomolecules present in aldehyde fixed samples, downstream methods can be performed to detect biomolecules present in the sample after the number of adducts and/or crosslinks have been reduced. Kool teaches that the methods include, after contacting a sample having aldehyde fixed biomolecules (e.g., a sample having formaldehyde fixed biomolecules, an aldehyde fixed biological sample, a formaldehyde fixed biological ample, an FFPE biological sample, and the like) with an adduct reversal agent, a step of detecting a biomolecule (e.g., RNA, DNA, and/or protein) in the biological sample. Any convenient detecting method can be used. Kool teaches that sample having a fixed biomolecules is contacted with an adduct reversal agent in solution buffered to a pH that is at or near the pKa of the adduct reversal agent. Kool teaches pH range of from 6-8 and also pH 6.5 to 7.7 (paragraph [0008]). Kool teaches treating fixed tissue with adduct reversal agent at a pH of 7 in Tris buffer (paragraph [0014]). Kool teaches treating fixed tissue at pH 7.0 (paragraph [0027]).
Kool teaches that in some cases, said detecting includes PCR, nucleic acid sequencing, in situ hybridization, and/or a protein detection method (e.g., an enzymatic detection assay, an antibody-based protein detection method, western blot, enzyme-linked immunosorbent assay (ELISA), immunohistology, an immunoenzymatic assay, immunofluorescence detection, fluorescent dye-based quantification (e.g. Qubit), spectroscopic quantification (e.g. Nanodrop) etc.).
As described above, Kool teaches treating fixed biological tissue with an adduct reversal agent (as for example, 2-aminobenzoic acid) for removing adducts and/or crosslinks for subsequent detection of biomolecules (e.g., RNA, DNA, and/or protein) in the biological sample with various detection methods including in situ hybridization, ELISA, enzymatic detection assay, immunohistochemistry or fluorescent dye-based quantification. Kool teaches detection of nuculid acid in biological tissue after treating fixed sample with adduct reversal agent, but however, does not specifically mention using probe that hybridizes target nucleic acid in the sample for the detection process.
Jonas teaches method for determining a location of a nucleic acid in a tissue section, the method comprising: (a) contacting the tissue section with an array comprising a plurality of capture probes, wherein a capture probe of the plurality of capture probes comprises (i) a spatial barcode and (ii) a capture domain that binds the nucleic acid (e.g. spatially tagging using probes with barcodes unique to each probe and polyT capture sequences; Figs. 7-8, Abstract, pgs. 1-3 and claim 1); (b) binding the nucleic acid to the capture domain of the capture probe (Figs. 7-8); (c) and identifying the presence or absence of the target nucleic acid in the tissue section based on the detection by the barcode sequence (Figs. 7-8 and pgs. 39, Example Ill, IV). Jonas teaches that the tissue can be a fixed tissues (page 27, line 23 to line 15 of page 28).
Therefore, given the fact that utilization of nucleic acid probe labeled with barcode label is known and common for detection and analysis of nucleic acid in a fixed tissue (Jonas) and given the fact that Kool teaches detection of biomolecules (e.g., RNA, DNA, and/or protein) in fixed biological tissue sample after treating with adduct reversal agent such as 2-aminobenzoic acid utilizing various detection methods including in situ hybridization, it would be obvious to one of ordinary skilled in the art before the effective filing date of claimed invention, to easily envisage detection of the adduct reversal agent (e.g. 2-aminobenzoic acid) treated fixed biological tissue with a probe (e.g. nucleic acid probe) have a barcode sequence that hybridizes to target nucleic acid in the 2-aminobenzoic acid treated sample for detection with the barcode sequence with a reasonable expectation of success..
In regards to claims 2 and 3, Kool teaches that the fixed biological tissue section is mounted on a substrate such as a glass slide (paragraph ([0054] and [0055]).
In regards to claims 4-5, Kool teaches that the fixed biological tissue is formalin fixed paraffin embedded biological sample (claims 24-26).
In regards to claim 6, Kool teaches treating the paraffin embedded fixed biological sample to remove paraffin prior to contact with the adduct reversal agent.
In regards to claims 7 and 33, as described above, Kool discloses de-crosslinking agent 2-aminobenzoic acid (
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) but however, Kool does not teach 2-amino-5-methylbenzoic acid (
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) as claimed in claim 7 and as encompassed by claim 33.
However, 2-aminobenzoic acid is very similar to the compound of 2-amino-5-methylbenzoic acid, differing by having a substitution group H in place of a methyl group at position 5 of 2-aminobenzoic acid. However, it was well established that the substitution of methyl for hydrogen on a known compound is not a patentable modification absent unexpected or unobvious results or that hydrogen and methyl are deemed obvious variants. In In re Wood, 582 F.2d 638, 199 USPQ 137 (CCPA 1978).
In regards to claim 9, Kool teaches contacting fixed tissue with adduct reversal agent at a concentration range or 15mM to 20mM (paragraph [0081]), which is within the range of 10mM to about 500mM as claimed in claim 9.
In regards to claim 10, Kool teaches contacting fixed biological tissue with an adduct reversal agent for a period of 30 minutes to 1 hour or 45 minutes to 1 hour, or at least 30 minutes, or at least 40 minutes or at least 1 hour or at least 1.5 hours (paragraph [0069]).
In regards to claim 11, Kool teaches treating fixed tissue with adduct reversal agent at a pH of 7 in Tris buffer (paragraph [0014]). Kool teaches treating fixed tissue at pH 7.0 (paragraph [0027]).
In regards to claims 12-13, Kool teaches various temperature ranges including a range of 15⁰C to 85⁰C (paragraph [0008] and [0070]), various pH including pH of 6.5-7.5 and various ranges of time periods including 20 minutes to 6 hours (paragraph [0008]). Kool teaches that the adduct reversal agent can be used at any convenient concentration and discloses various concentration ranges including 0.5mM to 200mM. Kool also teaches optimization of adduct reversal agent with various temperature, pH and time to get a suitable optimized condition (paragraph [0079]). Therefore, various temperatures, concentration ranges, incubation time and pH ranges would be obvious to one of ordinary skilled in the art for routine optimization. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454,456, 105 USPQ 233, 235 (CCPA 1955).
In regards to claim 31, as described above, Kool teaches detecting a biomolecule (e.g., RNA, DNA, and/or protein) in an aldehyde fixed biological tissue comprising: contacting the aldehyde fixed sample with an adduct reversal agent and detecting a biomolecule (e.g., RNA, DNA, and/or protein) in the adduct reversal agent treated aldehyde fixed biological tissue sample. Kool teaches that any convenient detecting method can be used. In some cases, said detecting includes PCR, nucleic acid sequencing, in situ hybridization, and/or a protein detection method (e.g., an enzymatic detection assay, an antibody-based protein detection method, western blot, enzyme-linked immunosorbent assay (ELISA), immunohistology, an immunoenzymatic assay, immunofluorescence detection, fluorescent dye-based quantification (e.g. Qubit), spectroscopic quantification (e.g. Nanodrop) etc.).
Claims 1-3, 5-7 and 9-13 and 31-35 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kool et al (US 2017/0283860A1) in view of Pedersen et al (WO2015188839; cited in the IDS filed 10/24/2023).
In regards to claims 1, 32, 34 and 35, Kool discloses method of de-crosslinking a formalin fixed tissue by contacting the fixed biological tissue with an adduct reversal agent (abstract), thereby de-crosslinking the fixed biological tissue (Abstract and Claim 1). Kool teaches that the adduct reversal agent is a compound selected from Table 1 (abstract and claim 9), which table 1 (page 11) discloses 2-aminobenzoic acid (
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) for adduct reversal. The compound 2-aminobenzoic acid reads on the formula (I) with the following selection: A is C(=O)OH, each of X1, X2, X3 and X4 is CH. Note that claim 35 does not further limit claim 34 limitation to at least one of the X1, X2, X3 or X4 to CRa but merely defines Ra.
Kool teaches that biological sample is a tissue sample that has been embedded in a convenient media, which includes but are not limited to: paraffin, paraffin-containing compounds, araldite, celloidin, DURCUPAN™. Kool teaches that the fixed specimens have been fixed with a variety of cross-linking agents, such as formaldehyde, paraformaldehyde, glutaraldehyde, or 1-ethyl-3-(3-dimethylaminopropyl) (paragraph [0064]). Kool teaches that the adduct reversal agent can catalyze the removal of adducts and/or crosslinks under relatively mild conditions (conditions that are not as damaging to biological samples, such as tissue samples, as the conditions used by other methods of crosslink removal). Thus, the subject methods result in less damage to biomolecules than other available methods for removing adducts and/or crosslinks. For example, the subject methods can result in much less damage to biomolecules than other available methods for removing adducts and/or crosslinks. Other methods use high temperatures and are carried out at pHs that are damaging to biomolecules such as nucleic acids and proteins. Thus, biomolecules can be “recovered” intact from aldehyde fixed samples using the subject methods. Because the subject methods can be carried out in relatively mild conditions (pH near neutral, temperatures near room temperature, short time frame of treatment, etc.), and inflict less damage on biomolecules present in aldehyde fixed samples, downstream methods can be performed to detect biomolecules present in the sample after the number of adducts and/or crosslinks have been reduced. Kool teaches that the methods include, after contacting a sample having aldehyde fixed biomolecules (e.g., a sample having formaldehyde fixed biomolecules, an aldehyde fixed biological sample, a formaldehyde fixed biological ample, an FFPE biological sample, and the like) with an adduct reversal agent, a step of detecting a biomolecule (e.g., RNA, DNA, and/or protein) in the biological sample. Kool teaches that sample having a fixed biomolecules is contacted with an adduct reversal agent in solution buffered to a pH that is at or near the pKa of the adduct reversal agent. Kool teaches pH range of from 6-8 and also pH 6.5 to 7.7 (paragraph [0008]). Kool teaches treating fixed tissue with adduct reversal agent at a pH of 7 in Tris buffer (paragraph [0014]). Kool teaches treating fixed tissue at pH 7.0 (paragraph [0027]).
Kool teaches that any convenient detecting method can be used. In some cases, said detecting includes PCR, nucleic acid sequencing, in situ hybridization, and/or a protein detection method (e.g., an enzymatic detection assay, an antibody-based protein detection method, western blot, enzyme-linked immunosorbent assay (ELISA), immunohistology, an immunoenzymatic assay, immunofluorescence detection, fluorescent dye-based quantification (e.g. Qubit), spectroscopic quantification (e.g. Nanodrop) etc.).
As described above, Kool teaches treating fixed biological tissue with an adduct reversal agent (as for example, 2-aminobenzoic acid) for removing adducts and/or crosslinks for subsequent detection of biomolecules (e.g., RNA, DNA, and/or protein) in the biological sample with various detection methods including in situ hybridization, ELISA, enzymatic detection assay, immunohistochemistry or fluorescent dye-based quantification.
Kool teaches detection of nucleic acid in biological tissue after treating fixed sample with adduct reversal agent, but however, does not specifically mention using probe that hybridizes target nucleic acid in the sample for the detection process.
Padersen teaches detection of analyte in a sample comprising contacting the sample with a detection molecule wherein the detection molecule comprises a binding molecule (BM), a linker and a label (La) (claim 20). Padersen teaches that the sample may be of various types including tissue sample and fixed tissue sample (claim 28). Padersen teaches that the binding molecule associates with, recognizes and/or binds to specific target (claim 6-8) wherein the binding molecules includes various binding partners including an antibody, a peptide, an oligonucleotide, a nucleic acid aptamer, a DNA aptamer and an RNA aptamer (claim 9). Paderson teaches that the label includes various detectable label including a DNA label, a nucleic acid label, a peptide label, a fluorescent label and an isotope label (claim 3) and specifically teaches that the nucleic acid label comprises a barcode region (claim 4) wherein the barcode region comprises a sequence of consecutive nucleic acids(page 48). Padersen teaches that in a particular embodiment the binding molecule of the detection molecule is an oligonucleotide, wherein said oligonucleotide preferably binds to DNA or RNA molecules inside a cell (pages 55 and 56). Paderson teaches detection of the detection molecule after binding to target in the sample comprises detecting the label by amplification of the label or sequencing the label (claim 25).
Therefore, given the fact that utilization of nucleic acid probe labeled with barcode label is known and common for detection and analysis of nucleic acid in a tissue sample of a fixed tissue (Padersen) and given the fact that Kool teaches detection of biomolecules (e.g., RNA, DNA, and/or protein) in fixed biological tissue sample after treating with adduct reversal agent such as 2-aminobenzoic acid utilizing various detection methods including in situ hybridization, it would be obvious to one of ordinary skilled in the art before the effective filing date of claimed invention, to easily envisage detection of the adduct reversal agent (e.g. 2-aminobenzoic acid) treated fixed biological tissue with a probe (e.g. nucleic acid probe) have a barcode sequence that hybridizes to target nucleic acid in the 2-aminobenzoic acid treated sample for detection of target in various tissue sample by detecting the barcode sequence with a reasonable expectation of success..
In regards to claims 2 and 3, Kool teaches that the fixed biological tissue section is mounted on a substrate such as a glass slide (paragraph ([0054] and [0055]).
In regards to claims 4-5, Kool teaches that the fixed biological tissue is formalin fixed paraffin embedded biological sample (claims 24-26).
In regards to claim 6, Kool teaches treating the paraffin embedded fixed biological sample to remove paraffin prior to contact with the adduct reversal agent.
In regards to claims 7 and 33, as described above, Kool discloses de-crosslinking agent 2-aminobenzoic acid (
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) but however, Kool does not teach 2-amino-5-methylbenzoic acid (
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) as claimed in claim 7.
However, 2-aminobenzoic acid is very similar to the compound of 2-amino-5-methylbenzoic acid, differing by having a substitution group H in place of a methyl group at position 5 of 2-aminobenzoic acid. However, it was well established that the substitution of methyl for hydrogen on a known compound is not a patentable modification absent unexpected or unobvious results or that hydrogen and methyl are deemed obvious variants. In In re Wood, 582 F.2d 638, 199 USPQ 137 (CCPA 1978).
In regards to claim 9, Kool teaches contacting fixed tissue with adduct reversal agent at a concentration range or 15mM to 20mM (paragraph [0081]), which is within the range of 10mM to about 500mM as claimed in claim 9.
In regards to claim 10, Kool teaches contacting fixed biological tissue with an adduct reversal agent for a period of 30 minutes to 1 hour or 45 minutes to 1 hour, or at least 30 minutes, or at least 40 minutes or at least 1 hour or at least 1.5 hours (paragraph [0069]).
In regards to claim 11, Kool teaches treating fixed tissue with adduct reversal agent at a pH of 7 in Tris buffer (paragraph [0014]). Kool teaches treating fixed tissue at pH 7.0 (paragraph [0027]).
In regards to claims 12-13, Kool teaches various temperature ranges including a range of 15⁰C to 85⁰C (paragraph [0008] and [0070]), various pH including pH of 6.5-7.5 and various ranges of time periods including 20 minutes to 6 hours (paragraph [0008]). Kool teaches that the adduct reversal agent can be used at any convenient concentration and discloses various concentration ranges including 0.5mM to 200mM. Kool also teaches optimization of adduct reversal agent with various temperature, pH and time to get a suitable optimized condition (paragraph [0079]). Therefore, various temperatures, concentration ranges, incubation time and pH ranges would be obvious to one of ordinary skilled in the art for routine optimization. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454,456, 105 USPQ 233, 235 (CCPA 1955).
In regards to claim 31, as described above, Kool teaches detecting a biomolecule (e.g., RNA, DNA, and/or protein) in an aldehyde fixed biological tissue comprising: contacting the aldehyde fixed sample with an adduct reversal agent and detecting a biomolecule (e.g., RNA, DNA, and/or protein) in the adduct reversal agent treated aldehyde fixed biological tissue sample. Kool teaches that any convenient detecting method can be used. In some cases, said detecting includes PCR, nucleic acid sequencing, in situ hybridization, and/or a protein detection method (e.g., an enzymatic detection assay, an antibody-based protein detection method, western blot, enzyme-linked immunosorbent assay (ELISA), immunohistology, an immunoenzymatic assay, immunofluorescence detection, fluorescent dye-based quantification (e.g. Qubit), spectroscopic quantification (e.g. Nanodrop) etc.).
Response to argument
Applicant's arguments and amendments filed 10/2/2025 have been fully considered but are not found persuasive to overcome the rejections under 35 USC 103.
In regards to rejections under 35 USC 103, Applicant considered the compound 4 of the reference of Kool as a lead compound and based on the consideration, argued that that there is no reason to modify the compound 4 of Kool to arrive at the compound of 2-aminobenzoic acid for use an adduct reversal agent.
Applicant stated that as amended, the scope of the compound of formula (I) has been amended to more closely align with the exemplified compounds, the compound 2-amino-5-methylbenzoic acid having the structure shown below, is presently elected:
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. The above arguments have fully been considered but are not found persuasive because claim 1 is not limited to 2-amino-5-methylbenzoic acid or closely aligned (very similar property?) compounds to 2-amino-5-methylbenzoic acid as formula (I) as claimed, encompasses distinct structures, as for example,
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,
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, and
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, to exemplify a few. The optional part of the claim is considered not a part of the claimed invention.
According to MPEP 2145 “Consideration of Applicant's Rebuttal Arguments,” arguing limitations which are not claimed is improper:
“Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. In reVan Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993) (Claims to a superconducting magnet which generates a “uniform magnetic field” were not limited to the degree of magnetic field uniformity required for Nuclear Magnetic Resonance (NMR) imaging. Although the specification disclosed that the claimed magnet may be used in an NMR apparatus, the claims were not so limited.); Constantv. Advanced Micro-Devices, Inc., 848 F.2d 1560, 1571-72, 7 USPQ2d 1057, 1064-1065 (Fed. Cir.), cert. denied, 488 U.S. 892 (1988) (Various limitations on which appellant relied were not stated in the claims; the specification did not provide evidence indicating these limitations must be read into the claims to give meaning to the disputed terms.); Ex parteMcCullough, 7 USPQ2d 1889, 1891 (Bd. Pat. App. & Inter. 1987) (Claimed electrode was rejected as obvious despite assertions that electrode functions differently than would be expected when used in nonaqueous battery since “although the demonstrated results may be germane to the patentability of a battery containing appellant’s electrode, they are not germane to the patentability of the invention claimed on appeal.”).
Applicant argued that as claim 1 recites a method that includes use of a chemical compound of formula (I), legal analysis under obviousness should be conducted in a manner consistent with the “lead compound” analysis, a two-part inquiry, whether a chemist of ordinary skill would have selected the asserted prior art compounds as lead compounds, or starting points, for further development efforts and whether the prior art would have supplied one of ordinary skill in the art with a reason or motivation to modify a lead compound to make the claimed compound with a reasonable expectation of success. Applicant argued that as stated by the court in Takeda v. Alphapharm, "in cases involving new chemical compounds, it remains necessary to identify some reason that would have led a chemist to modify a known compound in a particular manner to establish prima facie obviousness of a new claimed compound. Applicant argued that based in the teaching of Kool, a skilled artisan would have understood that compound 4 constitutes a “lead compound” and in contrast Office has selected compound 2 of Kool by stating “table 1” and compound 2 was chosen by the mere fact that it exists, which is an insufficient reason for identifying compound 2 as the “lead compound. Applicant argued that Kool fails to teach or suggest the use of its compound 2 as a lead compound and rather Kool shows that compound 2 as having mimimal activity in reversing hemiaminal formation. Applicant argued that Kool confirm the compound 4 is the most efficient and based on the disclosure of Kool, a skilled artisan would have not reason to select compound 2 as the lead compound. Applicant further argued that based on the disclosure of compound 4 as the lead compound by Kool, one would not propose a modification of the lead compound to arrive compound 3 or compound 2 as a lead compound. Applicant argued that compound 1, compound 2 and compound 8 of Kool have the lowest activity and by contrast compound 4 of Kool is shown as having maximal activity in reversing hemiaminal formation and thus based on the disclosure of Kool, one of ordinary skill in the art would have no reason to select compound 2 as the lead compound, particularly as the lead compound over compound 4.
The above arguments have fully been considered by are not found persuasive because the reference of Kool does not provide any teaching of suggestion for the modification of compound 4 to arrive the different compounds disclosed in the reference for utilizing as a de-crosslinking agent. The reference of Kool teaches various compounds useful of de-crosslinking of fixed tissue and tested some of the compound for effectiveness in de-crosslinking of some sample and based on this found compound 4 is efficient over the other disclosed compounds tested. The result does not provide compound 4 is the only compound that can be used for de-crosslinking, nor does the reference discourages utilizing other disclosed compound as a de-crosslinking agent because Kool clearly disclosed and claimed that adduct reversal agent is a compound comprising an aromatic ring and at least one of an amine and a proton-donating group (claim 1) and wherein the proton-donating group selected from a carboxylic acid group, a phosphoric acid group and sulfuric acid group and clearly teaches that that the adduct reversal agent is a compound selected from Table 1. Therefore, the compounds of Table 1 (which includes compounds 2, 3, 4..) have clearly been claimed for utilizing as an adduct reversal agent. The claiming of the disclosed compounds of Table 1 as an adduct reversal agent clearly indicates the reference of Kool does not teach away of other compound for using as an adduct reversal agent for various types of samples. Kool teaches that there are roughly 300 million tissue samples stored as formalin-fixed, paraffin-embedded (FFPE) specimens in the U.S. alone (paragraph [0099]) and one of ordinary skilled in the art understands that a single compound would not be useful for all types of aldehyde fixed tissues. The disclosure that Kool tested some compounds and found compound 4 provides improve result (i.e. a preferred compound) as adduct reversal agent with some tissue sample, but this does not provide or indicate that the other compounds disclosed and claimed are difunctional or non-usable as tissue reversal agent, because Kool claimed compounds of Table 1 for tissue reversal agents. According to MPEP §2123 disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). Kool discloses and claimed compound 2 including compound 4 as an adduct reversal agent, but discloses compound 2 is inferior to compound 4 for reversing certain adduct. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994).
Applicant’s arguments regarding rationale of obviousness rejection based on identifying of lead compound and modifying the lead compound to arrive compound 2 (amino benzoic acid) does not stand in this context because compound 2 is not a compound to be derived from compound 4 as the compound 2 has already been disclosed by Koon and claimed as one of an adduct reversal compound. Instant claim 1 claimed the disclosed compound of Koon (i.e. compound 2) in a method for adduct reversal and thus is not a new compound by Applicant which needed to be derived from compound 4 of Koon as Koon already disclosed compound 2 as an adduct reversal agent. The reference of Jones was not cited for modifying the adduct reversal compounds, nor does the reference of Koon teaches modification as compounds of Table 1, which also include compound 2 and is clearly claimed by Kool and an adduct reversal agent. Thus, all compounds of Table 1 of Kool (including compound 2) are obvious for the process claim as shown obvious by the combination of Kool in view of Jonas. The proper question would have been based on whether one would have expected unexpected advantage with the selection of compound 2 which is claimed in instant claim 1 but which is also claimed with among other compounds in claim 9 of Kool as a de-crosslinking agent. Instant claim 1 have been amended to delete the preferred compound of Kool but kept other compounds and argued on the basis of lead compound analyses but however, does not provide any unexpected advantages over using of other disclosed non-preferred compounds (as for example, aminobenzoic acid) of Kool’s claimed compounds as de-crosslinking agent. Moreover, as evidenced from the large number claimed compounds encompassed by various substitutions on formula (I), a particular substitution has not been disclosed as having an unexpected property. Whether the unexpected results, if any, are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at "elevated temperatures" using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100C).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SHAFIQUL HAQ/
Primary Examiner, Art Unit 1678