DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
Priority
The present application is a continuation of 15/521,213, filed 04/21/2027 (US Patent No. 11,371,096), which was filed as a proper National Stage (371) entry of PCT Application No. PCT/US2015/057007, filed 10/22/2015. PCT/US2015/057007 claims benefit under 35 U.S.C. 119(e) to provisional application No. 62/067,414, filed 10/22/2014.
Withdrawn Objections/Rejections
The previous objections to the claims are withdrawn in response to Applicant’s amendments to the claims.
Claim Objections
Claims 2 and 3 are objected to because of the following informalities:
Claim 2 recites “with one or more binding reagents corresponding to the Defensin alpha 3”, the language “corresponding to” is objected to because “corresponding to” generally means analogous or equivalent in character to, which is not consistent in meaning to having binding specific to or as binding is protein. It is suggested that Applicant amend the language in order to recite something such as, “one or more binding reagents for Defensin alpha 3” or “one or more specific binding reagents for Defensin alpha 3”.
Claim 3 recites “the binding reagent”, however claim 2 recites “one or more binding reagents”. It is suggested that applicant amend the language at claim 3 in order to recite “the one or more binding reagent” in order to use consistent claim language throughout the claims.
Appropriate correction is required.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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US 11,371,096 (15/521,213)
Claims 1, 12 and 14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11,371,096 in view of Fickett et al., Discovery and modeling of transcriptional regulatory regions, Current Opin. Biotechnol., 11, (2000), p. 19-24, Li et al., Upregulated expression of human alpha-defensins 1, 2 and 3 in hypercholesteremia and its relationship with serum lipid levels, 75, (2014), p. 1104-1109 and Sherman R. Abdominal Pain. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 86. Available from: https://www.ncbi.nlm.nih.gov/books/NBK412/.
Although the claims at issue are not identical, they are not patentably distinct from each other because ‘096 similarly recites a method of diagnosing and treating appendicitis in a patient, the method comprising (a) performing an assay to detect Defensin alpha 3 mRNA in a body fluid sample from a human subject with symptoms that mimic appendicitis (see claim 3 of ‘096, a body fluid that is blood), (b) comparing the level to a threshold level from a control human subject that has symptoms that mimic appendicitis but not having appendicitis, (c) determining (diagnosing) with appendicitis when the level if decreased compared to the control, and (d) treating the diagnosed patient by performing appendectomy (see ‘096 at claim 1).
‘096 differs in that although it recites patient presenting with symptoms that mimic appendicitis, and control with symptoms that mimic appendicitis, fails to recite that said symptoms are abdominal pain. Further ‘096 differs from the present claims in that it teaches detection of Defensin alpha 3 mRNA instead of protein.
As noted by Fickett et al., it is a reasonable first approximation to assume that when transcription levels (of mRNA) increase, the other effects on protein level remain the same, and the protein levels increase as well (Fickett, page 19, col. 2, para 1).
Further, with that knowledge (as cited from Fickett), specifically regarding Defensin alpha 3, it appears that protein expression levels of this protein are expected to correlate consistent with mRNA, see for example Li et al., Li measured alpha-defensin 3 gene and protein (referring to as HNP3) diagnostically (in relation to hypercholesteremia, see for example abstract). Diagnostically, both the gene and the protein consistent correlate (both the gene and the protein were increased in relation to hypercholesteremia, and decreased with treatment, see abstract, Figure 1 and Figure 2).
Sherman et al. teach pain in the abdomen is the single most important symptom of an acute abdominal pathologic process, see the reference suggesting there are many abdominal disease that produce this pain (see page 1, col. 1, para 1). See further page 1, col. 2, para 3, Sherman describes pain most often associated with acute appendicitis (see also page 3, col. 1 to col. 2 describing further initiation of appendicitis, and presentation of pain associated with appendicitis). The reference supports that it is well known that appendicitis presents with abdominal pain (see as cited above, and further throughout the reference, Sherman describe pain associated with appendicitis).
It would have been prima facie obvious to one having ordinary skill in the art to have modified ‘096 in order to have relied on Defensin alpha 3 protein in place of mRNA, because is a reasonable assumption that a protein’s expression will correlate with transcription levels (mRNA, Fickett), and because at least regarding Defensin alpha 3, the prior art supports consistency among trending levels for this biomarker (see Li et al., demonstrating increasing Defensin alpha 3 mRNA and increasing Defensin alpha 3 protein expression, considering increasing mRNA correlates with increasing protein level, one having ordinary skill would reasonably expect similarly decreasing mRNA would correlate with decreasing protein expression). One having ordinary skill in the art would have a reasonable expectation of success making this modification considering the prior art (particularly with this protein) shows consistency between mRNA and protein expression (so while this may not be the case for all proteins, it would be expected for this protein).
It would have been prima facie obvious to one having ordinary skill in the art to have modified the method of ‘096 such that patients presenting with symptoms that mimic appendicitis refer to those presenting with abdominal pain since abdominal pain is well known and most often associated with subject’s experiencing appendicitis (Sherman). One having ordinary skill would have a reasonable expectation of success relying on the symptom that is abdominal pain as the symptom mimic appendicitis because it was recognized in the art that abdominal pain is a commonly recognized leading symptom associated with appendicitis (based on Sherman).
Regarding claim 12, see ‘096 at claim 2.
Regarding claim 14, see ‘096 at claim 1.
Claim 2 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11,371,096 in view of Fickett et al., Li et al. Sherman, as applied to claim 1 above, and further in view of Buechler et al., WO99/35486.
‘096 recites a method substantially as claimed, but which fails to recite performing the method by introducing the sample into an assay instrument that contacts the sample with binding reagents for the biomarker to be assayed, the instrument generating a result and displaying the result in human readable form (claim 2).
However, see for example the invention of Buechler, teaching a test instrument (and performing methods on such instrument) for in home testing of patient sample, introducing sample into the instrument, generating the result and displaying the result in human readable format (see for example claims 28 and 48, see also page 4, lines 16-17 regarding output, page 2, lines 17-18, the instrument for detecting analytes such as proteins). Buechler et al. also teach their invention provides encoded tag on the assay device inserted into the instrument that allows ample, test or reagent information to be encoded, that fully automated embodiments allow this information to be stored along with test results and other pertinent information to create and maintain an accurate record of the tests and results, that minimizes chance of operator error in incorrectly identifying a sample or otherwise incorrectly entered information regarding a test (end of page 5 to page 6).
It would have been prima facie obvious to one having ordinary skill in the art to have performed the method of ‘096 using an automated assay instrument, as taught by Buechler et al., to accommodate in home testing, one further motivated to rely on the instrument of Buechler to further minimize risk of operator error (thereby improving the assay). One having ordinary skill would have a reasonable expectation of success because Buechler is teaching an immunoassay device capable of detection of analytes such as proteins (alpha defensin 3 is a protein analyte).
Claims 3 and 4 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11,371,096 in view of Fickett et al., Li et al., Sherman and JP2005-527235A.
‘096 teach a method substantially as claimed (assay for alpha defensin 3), however fails to teach the assay comprising antibody reagent (claim 3); and fails to teach sandwich assay (claim 4).
However, see for example, JP2005-527235A at end of page 22 to page 23, regarding detection of defensins, see specifically the reference teaches alpha defensin 3 can be detected by sandwich immunoassay using an antibody reagent.
It would have been further prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified ‘096 such that the assay is a sandwich immunoassay (antibody binding reagent) for alpha-defensin 3 as an obvious matter of use of a known assay for its art recognized purpose, namely because the prior art recognized this as an appropriate assay for detection of alpha defensin 3. One having ordinary skill in the art would have had a reasonable expectation of success using a known technique for detection of a biomarker it is known as detecting.
US 12,215,386 B2 (17/343,285)
Claims 1, 12 and 14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12,215,386B2 in view of Sherman R. Abdominal Pain. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 86. Available from: https://www.ncbi.nlm.nih.gov/books/NBK412/.
‘386 at claims 1 and 13 similarly recites methods of diagnosing and treating a diagnosed human subject with appendicitis comprising obtaining sample, detect expression (protein) of alpha defensin 3 in a blood sample (see ‘386 claim 2), comparing the detected level to the level in those not suffering appendicitis, and treating the human subject by appendectomy (removing the appendix, see claim 1).
‘386 differs from the present application in that ‘386 fails to teach the subject with abdominal pain, compared to control having abdominal pain but not appendicitis.
Sherman et al. teach pain in the abdomen is the single most important symptom of an acute abdominal pathologic process, see the reference suggesting there are many abdominal disease that produce this pain (see page 1, col. 1, para 1). See further page 1, col. 2, para 3, Sherman describes pain most often associated with acute appendicitis (see also page 3, col. 1 to col. 2 describing further initiation of appendicitis, and presentation of pain associated with appendicitis). The reference supports that it is well known that appendicitis presents with abdominal pain (see as cited above, and further throughout the reference, Sherman describe pain associated with appendicitis).
It would have been prima facie obvious to one having ordinary skill in the art to have modified the method of ‘386 to have performed the methods on those with abdominal pain since abdominal pain is well known and most often associated with subject’s experiencing appendicitis (Sherman), and because such pain can be a result of appendicitis or other disease. As such, one would be motivated to perform the method on those with abominable pain to distinguish those that need treatment for appendicitis from those that require treatment for other diseases. One having ordinary skill would have a reasonable expectation of success relying on the symptom that is abdominal pain because it was recognized in the art that abdominal pain is a commonly recognized leading symptom associated with appendicitis (based on Sherman).
Regarding claim 12, wherein the method provides sensitivity or specificity of at least 0.7 for the identification, see as cited above, ‘386 recites a detection method as claimed. Given that the method is consistent with the present claims, relies on the same biomarker for same diagnostic result, one would expect the method as taught by ‘386 achieve the same sensitivity or specificity.
Regarding claim 14, see ‘386 at claim 2, the sample including serum or plasma.
Claim 2 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12,215,386 in view of Sherman and Buechler et al., WO99/35486.
‘386 recites a method substantially as claimed, but which fails to recite performing the method by introducing the sample into an assay instrument that contacts the sample with binding reagents for the biomarker to be assayed, the instrument generating a result and displaying the result in human readable form (claim 2).
However, see for example the invention of Buechler, teaching a test instrument (and performing methods on such instrument) for in home testing of patient sample, introducing sample into the instrument, generating the result and displaying the result in human readable format (see for example claims 28 and 48, see also page 4, lines 16-17 regarding output, page 2, lines 17-18, the instrument for detecting analytes such as proteins). Buechler et al. also teach their invention provides encoded tag on the assay device inserted into the instrument that allows ample, test or reagent information to be encoded, that fully automated embodiments allow this information to be stored along with test results and other pertinent information to create and maintain an accurate record of the tests and results, that minimizes chance of operator error in incorrectly identifying a sample or otherwise incorrectly entered information regarding a test (end of page 5 to page 6).
It would have been prima facie obvious to one having ordinary skill in the art to have performed the method of ‘386 using an automated assay instrument, as taught by Buechler et al., to accommodate in home testing, one further motivated to rely on the instrument of Buechler to further minimize risk of operator error (thereby improving the assay). One having ordinary skill would have a reasonable expectation of success because Buechler is teaching an immunoassay device capable of detection of analytes such as proteins (alpha defensin 3 is a protein analyte).
Claims 3 and 4 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12,215,386 in view of Sherman and JP2005-527235A.
‘386 teach a method substantially as claimed (assay for alpha defensin 3), however fails to teach the assay comprising antibody reagent (claim 3); and fails to teach sandwich assay (claim 4).
However, see for example, JP2005-527235A at end of page 22 to page 23, regarding detection of defensins, see specifically the reference teaches alpha defensin 3 can be detected by sandwich immunoassay using an antibody reagent.
It would have been further prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified ‘386 such that the assay is a sandwich immunoassay (antibody binding reagent) for alpha-defensin 3 as an obvious matter of use of a known assay for its art recognized purpose, namely because the prior art recognized this as an appropriate assay for detection of alpha defensin 3. One having ordinary skill in the art would have had a reasonable expectation of success using a known technique for detection of a biomarker it is known as detecting.
Response to Arguments
Applicant's arguments filed 11/25/2025 have been fully considered.
Regarding remarks at page 4, the previous objections to the claims are withdrawn in response to Applicant’s amendments to the claims.
At remarks pages 4-5, Applicant argues the rejection of claims on the grounds of non-statutory double patenting, specifically that the rejection cites the patent, US 11,371,096, as reciting detection of Defensin alpha 3 protein. Applicant refers to the Certificate of Correction, the ‘096 patent actually claims Defensin alpha 3 mRNA. Applicant’s remarks are persuasive, see the amended grounds of rejection set forth in detail above. The claims are still rejected, see the newly cited prior art which supports Defensin alpha 3 mRNA and Defensin alpha 3 protein expression correlate consistently (the level of mRNA trends in correlation with protein expression). While this is not necessarily true for all mRNA/protein, in the case of Defensin alpha 3 protein, the prior art supports this is expected.
Regarding the second rejection of claim on the ground of non-statutory double patenting over US Patent 12,215,386, there are no specific argument in Applicant’s remarks.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLEN J MARCSISIN whose telephone number is (571)272-6001. The examiner can normally be reached M-F 8:00am-4:30pm.
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/ELLEN J MARCSISIN/Primary Examiner, Art Unit 1677