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.
Claim Objections
Claim 22 is objected to because of the following informalities: the claims lists the components of the system as “i.”, “j.” and “k.”, however there is no component a. – h. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Step 1:Independent claim 1 is directed toward a process and thus falls within a statutory category (see MPEP 2106 III. Summary of Analysis and Flow Chart).
Step 2A: The claim(s) recites step b. “using the individual levels of the protein biomarkers collectively to assess whether the patient may develop sepsis or to diagnose a patient as having sepsis”, which under its broadest reasonable interpretation can be performed in the mind, falling under the Mental processes grouping of abstract ideas and thus recites a judicial exception (see MPEP 2106.04(a)(2) III. Mental Processes).
This judicial exception is not integrated into a practical application because once it is determined that the patient may develop sepsis or is diagnosed with sepsis, nothing else is done. Furthermore, step a. of claim 1 itself recites an abstract idea because determining the biomarker levels under its broadest reasonable interpretation can be performed in the mind (see MPEP 2106.04(a)(2) III. Mental Processes) and the biomarkers themselves fall under Laws of nature, natural phenomena and products of nature as they are not being manipulated in any way (see MPEP 2106.04(b)). Furthermore, step a. amounts to mere data gathering and thus recites an insignificant extra solution actively (see MPEP 2106.05(g)). Dependent claims 2-9 and 11 merely recite additional biomarkers to be used in the abstract idea itself and the additional method steps of dependent claim 12 are also directed to a judicial exception. Dependent claims 13 and 14 are directed to using the biomarkers to effect treatment, however, the treatments are discussed with great generality (see MPEP 2106.04(d)(2) Particular Treatment and Prophylaxis in Step 2A Prong Two). Claims 16-21 fail to recite additional components that integrate the judicial exception into a practical application. Claim 22 recites “a computer processor configured to analyse data produced by the detector” however a general purpose computer for performing the judicial exception fails to quality as a particular machine and thus does not integrate the judicial exception into a practical application (see 2106.05(b)). Particular Machine.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the method steps of independent claim 1 are well-understood, routine, and conventional in the art as evidenced by primary reference Buechler (see MPEP 2106.05(d)).
Claims 1-22 are thus not patent eligible.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2 and 11-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by United States Patent Application Publication US 2007/0092911 to Buechler et al. (herein Buechler) as recited on the 12/9/22 IDS.
Regarding claims 1-2, Buechler discloses a method for analyzing a test sample (i.e., biological sample) obtained from a subject (i.e., patient), to diagnose the patient as having sepsis (see [0014-0016]). The method comprising the steps of: a. determining in the biological sample the amount of one or more biomarkers (see [0016]), wherein the individual biomarkers are combined into a marker panel (i.e., protein biomarker signature) (see [0019]); and using the biomarker levels to collectively diagnose a patient has having sepsis (see [0016]), wherein the biomarkers of the protein biomarker signature comprise at least four biomarkers (see [0016]) and wherein biomarkers used for the diagnosing sepsis include TNF-R1a, sTNFRSR11A, uPAR (see [0016]), Lymphotoxin B receptor (LTBR) (see [0021]), TNFRSF14 (see [0169]), CCL16, MPC-2, and MMP-1 (see [0176]).
Regarding claim 11, Buechler discloses all the limitations of claim 1 and discloses wherein the protein biomarker signature further comprises procalcitonin (PCT) (see [0185]), lactate, CRP, and D-dimer (see [0050]).
Regarding claim 12, Buechler discloses all the limitations of claim 1 and discloses a method of using the biomarkers to monitor a patient determined to have sepsis (see [0015]). Buechler discloses multiple determinations of one or more biomarkers can be made, and a temporal change in the markers can be used to rule in or out one or more diagnoses and/or prognoses, wherein a panel response (i.e., protein biomarker signature comprising individual biomarkers) over time may be indicative of a particular diagnosis, prognosis, etc. (see [0034, 0041]), which reads on both steps “a.” and “b.” of claim 12.
Regarding claim 13, Buechler discloses all the limitations of claim 1 and discloses a method of using the biomarkers to monitor treatment in a patient determined to have sepsis (see [0015]), wherein treatment includes antibiotics (i.e., antimicrobials) and corticosteroids (i.e., immunosuppressants) (see [0205]). Buechler discloses multiple determinations of one or more biomarkers can be made, and a temporal change in the markers can be used to rule in or out one or more diagnoses and/or prognoses, wherein a panel response (i.e., protein biomarker signature comprising individual biomarkers) over time may be indicative of a particular diagnosis, prognosis, etc. (see [0034, 0041]), which reads on both steps “a.” and “b.” of claim 13. The changes in prognosis and/or diagnosis over time would represent the effectiveness of said treatment.
Regarding claim 14, Buechler discloses all the limitations of claim 1 and discloses a method of using said biomarkers to determine a treatment regimen for a patient diagnosed with having sepsis (see [0054]), wherein the treatment regimen is a therapeutic and/or immunosuppressive agent (see [0205]). Buechler discloses multiple determinations of one or more biomarkers can be made, and a temporal change in the markers can be used to rule in or out one or more diagnoses and/or prognoses, wherein a panel response (i.e., protein biomarker signature comprising individual biomarkers) over time may be indicative of a particular diagnosis, prognosis, etc. (see [0034, 0041]), which reads on both steps “a.” and “b.” of claim 14. A change in diagnosis and/or prognosis with time would change the treatment regimen of said patient.
Regarding claims 16-18, Buechler discloses all the limitations of claim 1 and discloses a kit for analysis of said biomarkers, wherein said kit comprises devices (i.e., test elements) and reagents for the analysis of at least one test sample and instructions for performing the assay (see [0196]), wherein said reagents are labeled antibodies for selectively binding to each protein biomarker (see [0188-0189, 0198-0200]).
Regarding claim 19, Buechler discloses all the limitations of claim 18 and discloses wherein the test element is a lateral flow device (see [0192]).
Regarding claim 20, Buechler discloses all the limitations of claim 18 and discloses wherein the test element is a protein array (see [0190]).
Regarding claim 21, Buechler discloses all the limitations of claim 16 and discloses wherein the test sample is treated with an anticoagulant prior to testing (see [0208]).
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims 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 3 is rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application Publication US 2007/0092911 to Buechler et al. (herein Buechler) as cited on the 12/9/22 IDS in view of United States Patent Application Publication US 2005/0196817 to Kingsmore et al. (herein Kingsmore) as cited on the 12/9/22 IDS and International Publication WO 2017/122203 to Shen-Orr et al. (herein Shen-Orr).
Regarding claim 3, Buechler discloses all the limitations of claim 2, thus a protein biomarker signature comprising LTBR (see claim 1), CCL-16, and MCP-2, however, fails to disclose “wherein the protein biomarker signature consists of LTBR, CCL-16, CD28, FGF21 and MCP-2” as recited in the instant claim.
Kingsmore discloses biomarkers used to indicate sepsis, risk of sepsis, progression of sepsis, remission of sepsis, and risk of mortality (see abstract), wherein said biomarkers include FGF21 (see Figs. 5E and 6E).
Shen-Orr discloses a method of determining prognosis of a subject with sepsis by determining baseline levels of T-cell senescence in a subject (see abstract), wherein the T-cell senescence markers include CD28 (see pg. 4, line 20).
Buechler, Kingsmore, and Shen-Orr are analogous in the field of biomarkers for sepsis diagnosis/prognosis. The only difference between the prior art references and the claimed invention is the combination of said elements in a single reference. All the markers were known in the art, prior to the effective filing date, to be suitable biomarkers for the diagnosis/prognosis of sepsis, therefore no surprising effect would arise from the specific combination of the specific marker panel claimed. Therefore, it would have been obvious to one or ordinary skill in the art before the effective filing date to add FGF21 and CD28 to a biomarker panel of Buechler consisting of CCL-16, MCP-2, and LTBR in view of Kingsmore and Shen-Orr. See MPEP 2143 A. Combining Prior Art Elements According to Known Methods To Yield Predictable Results.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application Publication US 2007/0092911 to Buechler et al. (herein Buechler) as cited on the 12/9/22 IDS in view of United States Patent Application Publication US 2009/0203534 to Hossain et al. (herein Hossain) as cited on the 12/9/22 IDS and United States Patent Application Publication US 2009/0203534 to Hall et al. (herein Hall) as cited on the 12/9/22 IDS.
Regarding claim 4, Buechler discloses all the limitations of claim 2, thus a protein biomarker signature comprising MMP-1 (see claim 1), CCL-16, and MCP-2, however, fails to disclose “wherein the biomarker signature further comprises GALNT3, GT, LDL-R, LILRB5” as recited in the instant claim.
Hossain discloses a rapid, safe method for predicting sepsis using genes (see abstract), wherein said genes include GALNT3, LDL-R, and FABP6 (i.e., gastrotropin (GT)) (see Table 1).
Hall discloses a method for distinguishing between sepsis and SIRS comprising determining the amount of one or more biomarkers for sepsis (see abstract), wherein the one or more biomarkers includes LILRB5 (see Fig. 4).
Buechler, Hossain, and Hall are analogous in the field of biomarkers for sepsis diagnosis/prognosis. The only difference between the prior art references and the claimed invention is the combination of said elements in a single reference. All the markers were known in the art, prior to the effective filing date, to be suitable biomarkers for the diagnosis/prognosis of sepsis, therefore no surprising effect would arise from the specific combination of the specific marker panel claimed. Therefore, it would have been obvious to one or ordinary skill in the art before the effective filing date to add GLANT3, GT, LDL-R, and LILRB5 to a biomarker panel of Buechler comprising CCL-16, MCP-2, and MMP-1 in view of Hossain and Hall. See MPEP 2143 A. Combining Prior Art Elements According to Known Methods To Yield Predictable Results.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application Publication US 2007/0092911 to Buechler et al. (herein Buechler) as cited on the 12/9/22 IDS in view of United States Patent Application Publication US 2009/0203534 to Hossain et al. (herein Hossain) as cited on the 12/9/22 IDS and United States Patent Application Publication US 2009/0203534 to Hall et al. (herein Hall) as cited on the 12/9/22 IDS; and in further view of United States Patent Application Publication US 2005/0196817 to Kingsmore et al. (herein Kingsmore) as cited on the 12/9/22 IDS.
Regarding claim 5, the combination of references in regards to claim 4 renders obvious the invention of claim 4, however fails to disclose “wherein the protein biomarker signature further comprises FGF21” as recited in the instant claim.
Kingsmore discloses biomarkers used to indicate sepsis, risk of sepsis, progression of sepsis, remission of sepsis, and risk of mortality (see abstract), wherein said biomarkers include FGF21 (see Figs. 5E and 6E).
Buechler, Hossain, Hall, and Kingsmore are analogous in the field of biomarkers for sepsis diagnosis/prognosis. The only difference between the prior art references and the claimed invention is the combination of said elements in a single reference. All the markers were known in the art, prior to the effective filing date, to be suitable biomarkers for the diagnosis/prognosis of sepsis, therefore no surprising effect would arise from the specific combination of the specific marker panel claimed. Therefore, it would have been obvious to one or ordinary skill in the art before the effective filing date to add FGF21 to a biomarker panel comprising CCL-16, MCP-2, MMP-1 GLANT3, GT, LDL-R, and LILRB5 in Kingsmore. See MPEP 2143 A. Combining Prior Art Elements According to Known Methods To Yield Predictable Results.
Claims 6-9 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application Publication US 2007/0092911 to Buechler et al. (herein Buechler) as cited on the 12/9/22 IDS in view of United States Patent Application Publication US 2009/0203534 to Hossain et al. (herein Hossain) as cited on the 12/9/22 IDS and United States Patent Application Publication US 2009/0203534 to Hall et al. (herein Hall) as cited on the 12/9/22 IDS; and in further view of United States Patent Application Publication US 2005/0196817 to Kingsmore et al. (herein Kingsmore) as cited on the 12/9/22 IDS and International Publication WO 2017/122203 to Shen-Orr et al. (herein Shen-Orr).
Regarding claim 6, the combination of references in regards to claim 5 renders obvious the invention of claim 5, thus renders obvious a protein biomarker signature consisting of CCL-16, FGF21, GANT3, GT, LDL-R, LILB5, MCP-2, MMP-1 and TNFRSF11A (see claim 1), however, fails to disclose wherein the protein biomarker signature also consists of CD28 as recited in the instant claim.
Shen-Orr discloses a method of determining prognosis of a subject with sepsis by determining baseline levels of T-cell senescence in a subject (see abstract), wherein the T-cell senescence markers include CD28 (see pg. 4, line 20).
Buechler, Hossain, Hall, Kingsmore, and Shen-Orr are analogous in the field of biomarkers for sepsis diagnosis/prognosis. The only difference between the prior art references and the claimed invention is the combination of said elements in a single reference. All the markers were known in the art, prior to the effective filing date, to be suitable biomarkers for the diagnosis/prognosis of sepsis, therefore no surprising effect would arise from the specific combination of the specific marker panel claimed. Therefore, it would have been obvious to one or ordinary skill in the art before the effective filing date to add CD28 to a biomarker panel consisting of CCL-16, FGF21, GANT3, GT, LDL-R, LILB5, MCP-2, MMP-1 and TNFRSF11A in view of Shen-Orr. See MPEP 2143 A. Combining Prior Art Elements According to Known Methods To Yield Predictable Results.
Regarding claim 7, the combination of references in regards to claim 5 renders obvious the invention of claim 5, thus renders obvious a protein biomarker signature consisting of CCL-16, FGF21, GANT3, GT, LDL-R, LILB5, MCP-2, MMP-1 and TNF-R1 (see claim 1), however, fails to disclose wherein the protein biomarker signature also consists of CD244 as recited in the instant claim.
Shen-Orr discloses a method of determining prognosis of a subject with sepsis by determining baseline levels of T-cell senescence in a subject (see abstract), wherein the T-cell senescence markers include CD244 (see pg. 5, line 16).
Buechler, Hossain, Hall, Kingsmore, and Shen-Orr are analogous in the field of biomarkers for sepsis diagnosis/prognosis. The only difference between the prior art references and the claimed invention is the combination of said elements in a single reference. All the markers were known in the art, prior to the effective filing date, to be suitable biomarkers for the diagnosis/prognosis of sepsis, therefore no surprising effect would arise from the specific combination of the specific marker panel claimed. Therefore, it would have been obvious to one or ordinary skill in the art before the effective filing date to add CD244 to a biomarker panel consisting of CCL-16, FGF21, GANT3, GT, LDL-R, LILB5, MCP-2, MMP-1 and TNF-R1 in view of Shen-Orr. See MPEP 2143 A. Combining Prior Art Elements According to Known Methods To Yield Predictable Results.
Regarding claim 8, the combination of references in regards to claim 5 renders obvious the invention of claim 5, thus renders obvious a protein biomarker signature consisting of CCL-16, FGF21, GANT3, GT, LDL-R, LILB5, MCP-2, MMP-1 and TNF-R1 (see claim 1), however, fails to disclose wherein the protein biomarker signature also consists of CD28 as recited in the instant claim.
Shen-Orr discloses a method of determining prognosis of a subject with sepsis by determining baseline levels of T-cell senescence in a subject (see abstract), wherein the T-cell senescence markers include CD28 (see pg. 4, line 20).
Buechler, Hossain, Hall, Kingsmore, and Shen-Orr are analogous in the field of biomarkers for sepsis diagnosis/prognosis. The only difference between the prior art references and the claimed invention is the combination of said elements in a single reference. All the markers were known in the art, prior to the effective filing date, to be suitable biomarkers for the diagnosis/prognosis of sepsis, therefore no surprising effect would arise from the specific combination of the specific marker panel claimed. Therefore, it would have been obvious to one or ordinary skill in the art before the effective filing date to add CD28 to a biomarker panel consisting of CCL-16, FGF21, GANT3, GT, LDL-R, LILB5, MCP-2, MMP-1 and TNF-R1 in view of Shen-Orr. See MPEP 2143 A. Combining Prior Art Elements According to Known Methods To Yield Predictable Results.
Regarding claim 9, the combination of references in regards to claim 5 renders obvious the invention of claim 5, thus renders obvious a protein biomarker signature consisting of CCL-16, FGF21, GANT3, GT, LDL-R, LILB5, MCP-2, MMP-1 and U-PAR (see claim 1), however, fails to disclose wherein the protein biomarker signature also consists of CD28 as recited in the instant claim.
Shen-Orr discloses a method of determining prognosis of a subject with sepsis by determining baseline levels of T-cell senescence in a subject (see abstract), wherein the T-cell senescence markers include CD28 (see pg. 4, line 20).
Buechler, Hossain, Hall, Kingsmore, and Shen-Orr are analogous in the field of biomarkers for sepsis diagnosis/prognosis. The only difference between the prior art references and the claimed invention is the combination of said elements in a single reference. All the markers were known in the art, prior to the effective filing date, to be suitable biomarkers for the diagnosis/prognosis of sepsis, therefore no surprising effect would arise from the specific combination of the specific marker panel claimed. Therefore, it would have been obvious to one or ordinary skill in the art before the effective filing date to add CD28 to a biomarker panel consisting of CCL-16, FGF21, GANT3, GT, LDL-R, LILB5, MCP-2, MMP-1 and U-PAR in view of Shen-Orr. See MPEP 2143 A. Combining Prior Art Elements According to Known Methods To Yield Predictable Results. The claim recites “one of U-PAR or TRAIL-R2” and therefore the combination of Buechler, Hossain, Hall, Kingsmore, and Shen-Orr reads on the limitations of the claims.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application Publication US 2007/0092911 to Buechler et al. (herein Buechler) as cited on the 12/9/22 IDS in view of United States Patent Application Publication US 2014/0141435 to Garrett et al. (herein Garrett) as cited on the 12/9/22 IDS.
Regarding claim 22, Buechler discloses all the limitations of claim 16 and a detector for monitoring, measuring or detecting the individual levels of the protein biomarkers (see [0187-0196]), however, fails to disclose “a computer processor configured to analyse data produced by the detector” as recited in the instant claim.
Garrett discloses a method for distinguishing between sepsis and SIRS in a patient comprising determining the amount of one or more biomarkers for sepsis (see abstract), wherein computer-based algorithms can be used to carry out the methods of the current invention (see [0217]).
Buechler and Garrett are analogous in the field of biomarkers for sepsis diagnosis/prognosis. Therefore, it would have been obvious to one or ordinary skill in the art before the effective filing date to use a computer processor configured to analyse data produced by the detector for the benefit of analyzing a large amount of data with a high degree of certainty and accuracy (see [0217-0221]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHRYN E LIMBAUGH whose telephone number is (571)272-0787. The examiner can normally be reached Monday-Thursday 7:00-5:00.
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, Lyle Alexander can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KATHRYN ELIZABETH LIMBAUGH/Primary Examiner, Art Unit 1797