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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/1/2025 has been entered.
The amended claims filed 12/1/2025 are under consideration.
The amendments and arguments presented in the papers filed 12/1/2025 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 7/30/2025 listed below have been reconsidered as indicated.
a) The rejections of claim(s) 51-52 and 54 under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Chao (The Open Infectious Diseases Journal. 2010. 4:16-30); and claim(s) 53 under 35 U.S.C. 103 as being unpatentable over Chao (The Open Infectious Diseases Journal. 2010. 4:16-30), are withdrawn because Chao teaches a composition in which amount of JUP cDNA is elevated relative to the amount in a control sample, whereas the present claims encompass a composition have decreased amounts of JUP RNA and cDNA relative to healthy controls. See Fig. 188 of the instant specification.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New and grounds of rejection necessitated by amendment are detailed below.
Priority
The present application is filed as a divisional application of US application 17/481,622. The restriction requirement of the 17/481,622 application dated 7/19/2023 was between the following inventions:
I. Claims 1-7, drawn to compositions comprising a DNA polymerase, sample peripheral blood leukocyte cDNA having a cDNA expression profile characteristic of a subject with a clinical sign of systemic inflammatory response syndrome (SIRS), wherein the sample peripheral blood leukocyte cDNA comprises a Olfactomedin 4 (OLFM4) cDNA, and at least one oligonucleotide primer that hybridizes to the OLFM4 cDNA, classified in C12Q 2600/112.
II. Claims 8-14, drawn to compositions comprising a DNA polymerase, sample peripheral blood leukocyte cDNA having a cDNA expression profile characteristic of a subject with a clinical sign of systemic inflammatory response syndrome (SIRS), wherein the sample peripheral blood leukocyte cDNA comprises a Arginase 1 (ARG1) cDNA, and at least one oligonucleotide primer that hybridizes to the ARG1 cDNA, classified in C12Q 2600/112.
The present claims are drawn to compositions that are distinct from Groups I and II above because they require JUP cDNA and at least one oligonucleotide primer that hybridizes to the JUP cDNA. The present application is not filed in response to the restriction set forth in the 17/481,622 application. In order to obtain the benefit of 35 USC 121, claims must be formally entered, restricted in, and removed from an earlier application before they are filed in a divisional application. A claim drawn to a composition that in part requires JUP cDNA and at least one oligonucleotide primer that hybridizes to the JUP cDNA was not formally entered and removed from the 17/481,622 application. The present claims are additional claims that are not consonant in scope with the claims subject to the restriction in the parent 17/481,622 application, because the above noted claim was not part of the 17/481,622 application.
The present application is a voluntary divisional application and not in response to an Office requirement for restriction and the prohibition on nonstatutory double patenting rejection does not apply for the reasons provided above. See MPEP 804.01.
Claim Interpretation
Amended claim 51 recites “A composition comprising a synthesis and amplification mixture that comprises…sample peripheral blood leukocyte RNA from a subject with systemic inflammatory response syndrome (SIRS)”. The language “from a subject with systemic inflammatory response syndrome (SIRS)” is interpreted in view of the instant specification, in regards to JUP RNA/cDNA, as having a decrease in RNA/cDNA as compared to a “healthy” (Fig. 188). The language describes the source of the RNA/cDNA and thus, limits the structure of the RNA/cDNA. The claim broadly encompasses any RNA/cDNA sample having that structure (e.g., representative of a cDNA profile of peripheral blood leukocyte from a subject that has SIRS). See MPEP 2113.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 53 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
The following are new rejections necessitated by the amendments to the claims.
The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 53 constitutes new matter. The claim requires a combination of: DNA polymerase; reverse transcriptase; the specified RNA; the specified oligonucleotide reverse transcription primers; JUP cDNA; oligonucleotide amplification primers; and amplified JUP cDNA; and a probe that hybridizes to JUP cDNA.
The instant specification does not describe what essentially is composition with elements for a combined reverse transcription method and real-time PCR assay specific for JUP.
At best the instant specification cites a known two-step process for gene expression profiling as described in US 2007/0190540, in which the first step converts RNA into cDNA and amplifies it using multiplexed gene specific primers and the second step quantifies each individual gene by real time PCR. The compositions of that method are distinct from those of the present claims as it is a composition having all the elements for a single step reaction.
The Remarks cite to paragraphs 505, 513, 532 and 550 of the published application as the originally filed specification does not have 500 pages.
Paragraph 505 states:
It will also be assumed that the user interacts with application software executed by the processing system 210 via a GUI, or the like presented on the computer system 203. Actions performed by the computer system 203 are performed by the processor 401 in accordance with instructions stored as applications software in the memory 402 and/or input commands received from a user via the I/O device 403. The base station 201 is typically a server which communicates with the computer system 203 via a LAN, or the like, depending on the particular network infrastructure available.
Paragraph 513 states:
Additionally, the reference data may include details of one or more phenotypic traits of the individuals and/or their relatives. Phenotypic traits can include information such as the gender, ethnicity, age, or the like. Additionally, in the case of the technology being applied to individuals other than humans, this can also include information such as designation of a species, breed or the like.
Paragraph 532 states:
It will therefore be appreciated that this is an iterative technique that allows reference biomarkers capable of distinguishing the groups to be progressively identified with the ability of an additional N reference biomarkers to act as potential biomarkers being assessed, within each iteration. This process performs a relatively coarse filtering of reference biomarkers allowing groups of reference biomarkers with predictive performance above the threshold to be progressively removed from the reference biomarker collection and added to the potential biomarker collection.
Paragraph 550 states:
In the event that none of the potential biomarkers are excluded, the identified potential biomarkers are used as signature biomarkers, and an indication of the signature biomarkers is typically stored in a signature biomarker collection in the database 211. The measured activities from the reference individuals for the signature biomarkers can then be used to generate signatures for use in performing the clinical assessment at step 585. The signatures will typically define activities or ranges of activities of the signature biomarkers that are indicative of the presence, absence, degree, stage, or progression of a condition. This allows the signatures to be used in performing diagnostic and/or prognostic assessment of subjects.
None of the passages describes any synthesis or amplification reactions. These passages do not support the present scope of claim 53. There is no clear description of the claimed composition in the specification that demonstrates possession of the composition of claim 53.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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(s) 51, 53, 54 and 55 is/are rejected under 35 U.S.C. 103 as being unpatentable over Talwar (Physiol Genomics. 2006. 25:203-215) and McGoldrick (Journal of Virological Methods. 1999. 79(1):85-95).
The following are new rejection necessitated by the amendments to the claims.
Regarding claims 51, 53 and 55, Talwar teaches a first composition comprising:
RNA from PBMCs of four subjects challenged with intravenous endotoxin;
random primers (which would generate JUP cDNA if present);
a reverse transcriptase from the High Capacity cDNA Archive Kit; and
cDNA (corresponding to JUP RNA if present) (p. 204, Blood Cell Preparation and Total RNA Isolation; and Validation of Gene Expression Using Real-Time PCR).
Talwar further teaches a second composition comprising:
cDNA (corresponding to JUP RNA if present);
Taq DNA polymerase from a TaqMan Universal PCR master mix;
oligonucleotides for the amplification of target cDNAs;
amplified cDNAs; and
probes that hybridize the amplified cDNAs (p. 204, Validation of Gene Expression Using Real-Time PCR).
Talwar further teaches the amount of JUP RNA in the PBMCs of subjects challenged with intravenous endotoxin is decreased relative to subjects that were not challenged with endotoxin (Table 4, p. 211).
While the RNA and cDNA of Talwar is not specifically “from a subject with systemic inflammatory response syndrome (SIRS)”, the claimed composition must not be analyzed based on the source of the product but on a comparison of the claimed product and the product of the prior art. Here, the PBMCs of subjects challenged with intravenous endotoxin are analogous to those of a patient with SIRS.
It is further noted that Talwar observed increased: TLR5 (similar to depicted in Figs. 12 and 13 of the instant specification); C3AR1 (similar to depicted in Fig. 20 of the instant specification); MMP9 (similar to depicted in Fig. 50 of the instant specification); and ADM (similar to depicted in Fig. 66 of the instant specification).
Regarding claim 54, one would recognize the above compositions include dNTPs, otherwise, the reverse transcription and amplification of Talwar would not have occurred.
Talwar does not specifically teach a single composition with all the claimed elements or primers and probes specific for JUP cDNA.
Regarding claims 51, 53, 54 and 55, McGoldrick teaches a composition comprising: primers for specific cDNA targets; dNTPs; Taq DNA polymerase; an RNA sample; outer primers for making cDNA; MMLV; reverse transcribed cDNA and amplified cDNA (p. 89, 2.4.3. RT-nPCR). McGoldrick further teaches the composition includes a TaqMan probe that hybridizes with cDNA (p. 89, 2.4.4. RT-nPCR-TaqMan).
McGoldrick does not specifically teach the claimed primers and probes specific for JUP RNA/cDNA.
It would have been prima facie obvious to the ordinary artisan to have modified the compositions of Talwar by combining them as described by McGoldrick to have arrived the composition of McGoldrick. One would have been motivated to include primers for creating JUP cDNA, amplified JUP cDNA and a probe for amplified JUP cDNA in order to validate the observed decrease in JUP RNA/cDNA observed. One would have been motivated to generate the composition of McGoldrick because it allows for cDNA creation, amplification and detection in a single tube.
Alternatively, one would have modified the composition of McGoldrick by including primers and probes for JUP RNA/cDNA in order to monitor the levels of JUP RNA/cDNA which is known to be altered after exposure to endotoxin as established by Talwar.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682
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