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 .
Election/Restrictions
Applicant's election with traverse of group I, claims 1-12, TXN, BCL6, BCAT1, LCN2, UBE2L6, HLA-DPB1, and oseltamivir in the reply filed on 05/08/2026 is acknowledged. The traversal is on the ground(s) that it would not be unduly burdensome to perform a search on all of the claimed together in the application. This is not found persuasive because the restriction requirement is required under 35 USC 121 and 372. In the instant case the claims lack unity of invention as addressed in the office action mailed 11/26/2025. When two groups lack unity of invention a restriction is proper. Additionally even arguendo, searching group I and group II is a burden as each invention would have a different field of search, different search strategies, different classification, electronic resource and prior art applicable to one invention would not likely be applicable to another invention and the inventions are likely to raise different non-prior art issues under 35 USC 101 and 35 USC 112, first paragraph. As such there is an undue burden to examine group I and group II, along with group I and group II lacking unity of invention.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-12 and 20-21 are under examination with respect to TXN, BCL6, BCAT1, LCN2, UBE2L6, and HLA-DPB1. Claim 11 and 12 are under examination with regard to oseltamivir.
Drawings
The drawings file 03/16/2023 are acceptable.
Claim Objection
Claim 6 is objected to because of the following informalities: the claim recites a severe or mile score which appears to be a typographical error. The claim should recite severe or mild score. Appropriate correction is required.
Claim 12 is object to because of the following informalities: the claim comprises a period in the middle of the claim. A claim should only comprise one sentence and should not comprise a period in the middle of the claims. Appropriate correction is required.
Improper Markush
Claims 1, 7-8 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of HLA-DPB1, BCL6, NQO2, ORM1, DEFA4, KLRB1, CTSG, LCN2, AZU1, TXN, DOK2, CCL2, CEACAM8, AQP9, KLRG1, KLRD1, EPHX2, GRN, CAMP, TLR2, ANXA3, SLPI, KLHL2, CEP55, SRGN, TRIP13, PRC1, TCEAL9, EXOC2, BCAT1, PRF1, PRSS23, TRIB2, FURIN, ACSL1, EZH1, HMMR, UBE2L6, CASP7, OLR1, BUB3, SCANDi, ITGB7, DOK3, SIDT1, RAD23B, KIF15, ARHGAP45, MAP3K4, ATPBB4, IGFBP2, IFITM2, USP11, SMYD2, PFKFB4, VAMPS, ELL2, POMP, H1-0, ADM, SSR2, VRK2, IL7R, FBLN5, MAFB, TRAF5, CDT1, OASL, TRAF3IP3, TMEM123, TLN1, CCR7, LTBP3, CHMP7, PITPNCi, NUCB1, RBM15B, FAM8A1, BTBD7, ATG3, BCL2A1, IFITM1, DDB1, BCL2L11, LAPTM4A, KIF23, TYK2, PIK3R1, BANF1, TRIM28, SOCS6, LRBA, ANXA2, IFTM3, CREG1, and NAPA is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
A Markush claim contains an ‘‘improper Markush grouping' ' if: (1) the species of the Markush group do not share a ‘‘single structural similarity,' ' or (2) the species do not share a common use. Members of a Markush group share a ‘‘single structural similarity' ' when they belong to the same recognized physical or chemical class or to the same art-recognized class. Markush group applies when there is an expectation from the knowledge in the art that the members of the class will behave in the same way in the context of the claimed invention. There is no evidence that the members of the claimed classes encompasses a wide range of RNA transcripts encoded by a wide range of genes will behave in the same way in the context of the claimed invention. There is no common use that flows from the substantial structural feature, see MPEP 2117 (II) B. There is no structural feature that is common use for viral infection of developing severe symptoms.
The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: each member of the RNA transcripts of the claimed genes are structurally unique relative to one another. There is no disclosed common substantial structural feature. The only structural similarity present is that all detected transcripts are part of nucleic acid molecules. The fact that the transcripts comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated with gastric cancer. Accordingly, while the different markers are asserted to have the property of being indicative of developing severe symptoms from a viral infection, they do not share a single structural similarity. Additionally there is no expectation from the knowledge in the art that the members of the class will behave in the same way in the context of the viral infection, in other words there is no expectation from the art that each of the claimed transcripts will be associated with predisposition to severe symptoms in virally infected subject.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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 1-12 and 20-21 rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature and an abstract idea without significantly more.
Claim 1 recites a law of nature/natural phenomena. Claim 1 recite determining a virally infected subject’s risk of developing a severe symptom by measuring amount of RNA transcripts of TXN, BCL6, BCAT1, LCN2, UBE2L6, and HLA-DPB1. Claim 7 recites the elected genes. Claim 8 recites virally infected subject risk of developing severe infection based on gene expression data obtained by measuring RNA transcripts of TXN, BCL6, BCAT1, LCN2, UBE2L6, and HLA-DPB1. The recited relationship of the RNA transcripts with risk of developing severe symptoms is a natural phenomenon that exists apart from any human action. This type of correlation is a consequence of a natural process.
Claim 1 recites an abstract idea that is a mental process and mathematical. The recitation of based on the gene expression data providing a report indicating the subjects risk of developing severe symptoms in claim 1 is a mental process. The claim further requires increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1. The determination of increased and decreased expression is a mental process which requires a comparison to determine an increase or decrease. The broadest reasonable interpretation is a step that can be accomplished mentally be evaluating data and critical thinking process such that one mentally reads information in a database or report regarding expression then draws a mental conclusion.
Claim 6 recites calculating a severe to mild score based on the amounts of the RNA transcript, wherein the score indicates the probability the subject will develop severe symptoms, which encompasses both mathematical calculation and mental process. The score is a mathematical calculation, the recitation of based on the amount of RNA transcript is a mental process as this requires a mental comparison of the RNA transcript. The recitation of wherein the score indicates the probability that the subject will develop severe symptoms encompasses a law of nature, the RNA transcripts are a natural consequence of the viral infection and developing severe symptoms.
Claim 8 recites report is based on gene expression data obtained by measuring amount of RNA transcript of TXN, BCL6, BCAT1, LCN2, UBE2L6, and HLA-DPB1, wherein increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1 increased subject risk of developing symptoms. These steps encompass a mental process and natural correlation which is a law of nature. The comparison of expression is a mental process and the association of gene expression with developing severe symptoms is a law of nature. These judicial exceptions are not integrated into a practical application because the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application. For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or
improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological
environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
Claim 1 recites measuring amount of RNA transcripts and based on gene expression data providing a report indicating the subjects risk of developing severe stomps. The step of generating a report is post solution activity that is not integrated into the claim as a whole. The step of generating a report does not amount to an inventive concept.
Claim 8 is a method of treating a subject having a viral infection comprising receiving a report and treating the subject based on whether the subject has a high risk of developing severe symptoms. The step of treating is conditional and not specific. The step of treating is dependent on developing severe symptoms and the step of treating comprises any treatment, including treatment not specific to viral infection. Additionally the step of administering intensive care as recited in claim 9-10 encompasses monitoring functions and does not result in administering a specific treatment. The step of administering treatment in claims 11-12 are not specific and do not integrate the judicial exceptions. These additional elements of administering antiviral therapy do not apply the judicial exception.
As mentioned above, a claim limitation can integrate a judicial exception by applying or using the judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. When evaluating this consideration one must the following:
(i) the particularity or generality of the treatment or prophylaxis limitation;
(ii) whether the limitations have more than a nominal or insignificant relationship to the exception; and
(iii) whether the limitations are merely extra solution activity or field of use.
The steps of “treating the subject based on whether the subject has a high risk of developing severe symptoms” is not particular is not particular i.e., specifically identified so that it does not encompass all applications of the judicial exception. In other words the claims broadly encompass any and all therapy regimens and further does not require administering the therapy to the subject as the claims recite treating the subject based on whether the subject has a high risk of developing severe symptoms. Additionally claims that recite specific antiviral therapy are not specific and do not require the subject to have a specific expression level and administering to the subject the expression level a specific therapy, for example. The treatment limitations do not appear to have a significant relationship to the exception.
In addition to the judicial exceptions the claims recite measuring steps for RNA transcript (claim 2-4) and sample type (claim 5). These additional steps/elements are not considered to integrate the judicial exception into a practical application because they merely add insignificant extra-solution activity (data gathering) to the judicial exception and further limit the judicial exception.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than well-understood, routine, and conventional activities in the art and do not add something significantly more so as to render the claims patent -eligible. The step of identifying elevated levels of increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1 and generating a report merely instructs a scientist to use well-established routine and conventional nucleic acid techniques to gather samples for diagnostic analysis. As address in the instant specification methods of expression analysis employ conventional methods within the skill in the art (See pg. 8 lines 27-34). The specification addresses the measuring step can be done using any suitable method and demonstrates these methods are routine and conventional in the art (see pg. 16, lines 26-pg 17 lines 1-7).
The step of measuring RNA transcript levels of BCL6, LCN2, TXN, BCAT1, UBE2L6 HLA-DPB1 in a sample constitutes a data gathering step required to apply the law of nature/natural phenomenon. It is acknowledged that the claims name particular biomarkers, BCL6, LCN2, TXN, BCAT1, UBE2L6 HLA-DPB1 whose level is to be determined however the claims do not require a particular, non-conventional primer or probe consisting of or comprising a specific nucleotide sequence or any other specific reagent that is used to accomplish such determining such that the claims would recite significantly more than the judicial exception. The targets to be detected are part of the judicial exception and thereby the naming of the targets does not add something “significantly more” to the recited judicial exceptions.
The additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide inventive concept necessary to render the claims patient eligible. There is no combination of elements in this step that distinguishes it from well-understood, routine and conventional data gathering activity engaged in by scientists prior to applicant’s invention and at the time the application was filed. Many cited prior art references in this record demonstrate that these techniques were conventional at the time of the invention. The specification discloses that the biomarker expression data can be obtained from publicly available data sets (GSE,,,,). Thus the prior art and specification demonstrates it was routine, well-known and conventional in the art to determine expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 HLA-DPB1 in biological samples. The dependent claims do not provide significantly more to the claims outside of the judicial exception as they encompass conventional techniques as described in the instant specification as noted above.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-12 and 20-21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites based on the gene expression data, claim 6 recites based on the amount of the RNA transcript, and claim 8 recites based on the gene expression data. It is unclear what is encompassed and required for “based on”. Claim 1 and 8 recite receiving a report based on the gene expression data however it is unclear what is encompassed by the report that is based on gene expression. It is unclear if this encompasses gene expression, a conclusion of the expression data, a conclusion of subjects risk or some other derivation of the gene expression. Therefore the recitation of “based upon” renders the claim indefinite and one of skill in the art cannot determine the metes and bound of the claim and would not be reasonably apprised of infringing on the claimed invention. Additionally the claims require providing a report wherein increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1 however it is unclear how increased and decreased expression is determined for the report. Is the increased expression and decreased expression compared to a control or compared to a previous report? It is unclear how the report is provided based on expression data and how this expression data is determined. Therefore the recitation of “based upon” and providing a report wherein increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1 renders the claim indefinite and one of skill in the art cannot determine the metes and bound of the claim and would not be reasonably apprised of infringing on the claimed invention.
Claim 4 recites the limitation "the same" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 4 depends from claim 1 and it is unclear what labeling of RNA or cDNA made from the same refers to or encompasses.
Claim 9 recites the limitation "the comparing the risk to a threshold" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 9 depends form claim 8 and claim 8 does not recite or require comparing or determining risk. The administering step in claim 9-12 is unclear because it is dependent on the comparing risk to threshold from claim 8 however claim 8 does not require a comparison step and it is therefore unclear what is required for the administering steps in claim 9-12.
Claim 11 recites the limitations of “N4” and “N3”. This recitation renders the claim indefinite. It is unclear what is encompassed by N4 or N3. The claim requires administering a therapeutic dose of an antiviral therapy however N3 and N4 are not antiviral therapy and it is unclear what is encompassed N3 and N4.
Regarding claim 12 the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. Additionally claim 12 recites exemplary antiviral agents include and this recitation renders the claim indefinite because it is not clear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 12 contains the trademark/trade name Tamiflu, Relenza, vitravene, arbidol, atripla, combivir, imunovir, nexavir, norvir, trizivir, truvada, valtrex, and viramidine. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe antiviral therapies and, accordingly, the identification/description is indefinite.
Claim 12 is vague and indefinite for the recitation of multiple parentheticals. Parenthetical make the claim indefinite because it is unclear whether the information in the parenthesis has the same, less or more weight as the rest of the claim language. The information in the parenthesis is not equivalent to the information that it defines. For example the recitation of “atripla (fixed dose drug)” does not contain equivalent information as atripla is an antiviral drug and fixed dose drug refers to a larger class of drugs. This rejection may be overcome by deleting the information in the parentheses.
Claims 2-7 and 9-12 depend from claim 1 and claim 8, respectively. The claims are indefinite for the reasons applied to claim 1 and claim 8.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 9-12 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 9 depends from claim 8. Claim 9 recites wherein the comparing the risk to a threshold. Claim 8 recites a method for treating a subject comprising receiving a report and treating the subject based on whether the subject has a high risk of developing severe symptoms. Claim 8 does not require a comparison step or comparing risk to a threshold. Claim 9 does not further limit claim 8. Claims 10-12 depend from claim 9 and do not further limit claim 8 from which claim 9 depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-12 and 20-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A method for treating a subject having an influenza viral infection comprising measuring increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1 in a blood sample from the subject and is compared to a control where the control is a level of gene expression in a blood sample from a healthy human subject; and
administering oseltamivir to the subject with an increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1.
does not reasonably provide enablement for the breadth of the methods as claimed which encompass the analysis of any viral infection, any severe symptom and treating with any antiviral therapy, the analysis based on gene expression of the elected genes and the comparison of gene expression.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The claims are drawn to a method comprising determining a virally infected subject risk of developing severe symptoms by measuring the amount of RNA transcript of BCL6, LCN2, TXN, BCAT1, UBE2L6, HLA-DPB1 and decreased expression of HLA-DPB1 and based gene expression data providing a report indication risk of developing severe symptoms by increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1. Additional claims are drawn to method of treating a subject having a viral infection comprising receiving a report wherein the report is based on gene expression obtained by measuring the amount of RNA transcript wherein increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1 increased subject risk of developing severe symptoms and treating the subject based on high risk of developing severe symptoms. The breadth of the claims encompasses the analysis of gene expression relative to any value, any severe symptom, any viral infection, and any antiviral therapy.
The disclosure provides an analysis of gene expression related to different clusters of respiratory viruses. Relevant to the instant rejection, the specification provides an analysis of gene expression data sets from human subjects to discover markers of severe viral infections using influenzas, RSV or HRV compared to healthy controls (see fig 3, pg. 10-13) in blood samples. The specification teaches severe symptoms of respiratory viral infection is identified when increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1 compared to levels in a healthy control (p.10-13).
The specification identifies methods of administering and dosage of administering therapeutics are known in the art or can be derived from the art (see pg. 20) however the claims encompass a large genus of therapies that are not known in the art or taught in the instant specification. For example the claims encompass N3 or N4 therapies (claim 11), fusion inhibitor, interferons, fixed dose combination, interferon type I, II, or III of which are not known in the art and not taught in the specification to treat any severe symptom in any viral infection. With regard to the elected therapy, oseltamivir, this therapy only is effective in treating influenza viral infections and is not enabled to treat any other severe symptom of viral infection, for example, HIV, HPV, Ebola, coronaviruses, etc.
The specification does not provide any analysis of data of comparison of gene expression to any control data other than a healthy subjects. The specification not teach any antiviral therapy and any viral infection other than influenza therapy association with the elected genes.
While methods of detecting biomarkers are known in the art, methods of correlating biomarkers with a phenotype (severe symptoms of viral infection) are highly unpredictable.
The claims are drawn to methods of determining risk of severe symptoms based on the expression levels of RNA transcripts in a sample.
The claims are drawn to methods of detecting tuberculosis based on the expression levels of biomarkers in a biological sample. The claims broadly encompass the analysis of ANY type of biological sample. It is highly unpredictable if the expression levels observed in whole blood samples can be extrapolated to other sample types encompassed by the claims. The prior art of Whitehead (Genome Biology 2005 Vol 6 Issue 2 Article R13) teaches that variation in gene expression is extensive among tissues (abstract). The specification teaches increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1 in whole blood samples obtained from patients with active tuberculosis. There is no analysis in the specification on the levels of these biomarkers in other sample types (sputum, urine, hair, lung tissue, etc.) obtained from patients with respiratory infections (RSV, HRV, influenza) (see pg. 24) Thus in the absence of evidence to the contrary it is highly unpredictable if increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1 are differentially expressed in additional sample types obtained from patients with any viral infection. The specification only provides enablement for the analysis of whole blood samples in RSV, HRV, influenza.
The claims are drawn to methods of detecting severe symptoms of viral infection based on the increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1 in a biological sample. However the is no evidence in the specification that the gene set can successfully distinguish between severe symptoms versus mild systems in any viral infection. The specification discloses analysis of only respiratory viruses of RSV, HRV, and influenza. Yet this is broadly encompassed by the claims and would be highly unpredictable in the absence of evidence to the contrary.
Finally it is highly unpredictable if the claimed method can be practiced using reference value ranges for the biomarkers for ANY type of control subject. As discussed above the claims do not set forth what the control subject is and broadly encompass ANY control subject, including subjects that are healthy, have active infection, have any viral infection, have cancer, have HIV, have other disease etc. However the teachings in the specification only provide support for a method wherein a subject with increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1 in comparison to the levels in samples obtained from healthy control subjects. It is highly unpredictable if increased expression of BCL6, LCN2, TXN, BCAT1, UBE2L6 and decreased expression of HLA-DPB1 when compared to ANY control encompassed by the claims would be associated with any severe symptom of a viral infection.
A large and prohibitive amount of experimentation would be required to make and use the claimed invention. Such experimentation would require case: control analysis to establish that any sub combination of gene expression marker, in a variety of samples for a variety of viral infections as compared to any control, is indicative of severe infection.
Taking into consideration the factors outlined above, including the nature of the invention and breadth of the claims, the state of the art, the level of skill in the art and its high level of unpredictability, the lack of guidance by the applicant and the particular examples, it is the conclusion that an undue amount of experimentation would be required to make and use the claimed invention in the full scope as claimed.
Claim Rejections - 35 USC § 102
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 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, 4-7, 20-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu (BMC Bioinformatics, 2016, vol 17, pp 1-15).
Liu teaches analysis of gene expression in subject using Affymetrix Human U133 A 2.0 Gene chip that were prepared from total RNA (see Methods, pg. 2). The subjects were infected with HRV, RSV, H1N1, and H3N2 (see viral challenge study model, pg. 2) The expression level of each gene of the elected gene combination was detected in the method of Liu and is provided in the data that can be accessed via the Gene Expression Omnibus repository (GSE73072), which represents providing a report. Liu teaches subject were syntomic or asymptomatic, symptomatic subject encompass severe symptoms as indicated in specification by fever, headache, muscle aches. Liu further teaches prediction algorithms (see pg. 46) which includes a score based on the amount of RNA transcripts to indication probability (claim 6). It is noted that claim require providing a report indicating the subject risk of developing symptoms, the claims do not require detecting an increase or decrease of TXN, BCL6, BCAT1, LCN2, UBE2L6, and HLA-DPB1. As such Liu measuring RNA expression of TXN, BCL6, BCAT1, LCN2, UBE2L6, and HLA-DPB1 and based on the expression provides a report indicating risk, which is the only active process step of the claims. It is noted that the prior art dataset is recited as a dataset that is included in the retrospective analysis of the instant disclosure (see pg. 24).
The claims are enabled to the extent of the specification in order to provide compact prosecution Liu is provided as it teaches the positive active steps of the claims.
Claims 1-2, 4-7, 20-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wilk (Nature Medicine, vol 26, 2020, pp 1070-1076) (cited on IDS).
Wilk teaches analysis of gene expression in subject using single cell transcriptomic in severe COVID-19. Wilks teaches massively parallel single cell RNA sequencing on blood sample from hospitalized patients with RT-PCR confirmed SARS-Cov 2 (see pg. 1070, 1st column) (claim 2, 4-5). The expression level of each gene of TXN, BCL6, BCAT1, LCN2, UBE2L6, and HLA-DPB1 was detected in the method of Wilks and is provided in the data that can be accessed via the Gene Expression Omnibus repository (GSE150728), which represents providing a report (see pg. 1078). Wilks teaches subjects were hospitalized (severe symptoms). Wilks teaches score were determined based on expression level (see pg. 1073, 1st column). It is noted that claim require providing a report indicating the subject risk of developing symptoms, the claims do not require detecting an increase or decrease in TXN, BCL6, BCAT1, LCN2, UBE2L6, and HLA-DPB1. As such Wilks teaches measuring RNA expression of TXN, BCL6, BCAT1, LCN2, UBE2L6, and HLA-DPB1 and based on the expression provides a report indicating risk, which is the only active process step of the claims. It is noted that the prior art dataset is recited as a dataset that is included in the retrospective analysis of the instant disclosure (see pg. 25).
The claims are enabled to the extent of the specification in order to provide compact prosecution Wilk is provided as it teaches the positive active steps of the claims.
Claims 1, 4-7, 8-12, and 20-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ramillo et la. (Blood, 2007, vol 109, pp 2066-2077).
Ramillo teaches analysis of gene expression in blood samples from subject with viral infections (see patient information) including influenza. Ramillo teaches total RNA was isolated and hybridization was performed using Affymetrix HGU133 gene chips (see methods and fig 6) (claim 4-5). Ramillo teaches data obtained for all microarray was deposited in the public gene expression database GEO, GSE6269. The expression level of each gene of TXN, BCL6, BCAT1, LCN2, UBE2L6, and HLA-DPB1was detected in the method of Ramillo and is provided in the data that can be accessed via the Gene Expression Omnibus repository (GSE6269), which represents providing a report (see pg. 1078). The Affymetrix U133 gene chip plus 2 comprises probes for TXN, BCL6, BCAT1, LCN2, UBE2L6, and HLA-DPB1 and therefore will comprise measuring mRNA transcript levels of the elected genes. Ramillo teaches subjects were hospitalized (severe symptoms) (see patients characteristics). Ramillo teaches administering oseltamivir (see table 2). It is noted that claim require providing a report indicating the subject risk of developing symptoms, the claims do not require detecting an increase or decrease in the elected gene. As such Ramillo teaches measuring RNA expression of TXN, BCL6, BCAT1, LCN2, UBE2L6, and HLA-DPB1 and based on the expression provides a report indicating risk, which is the only active process step of the claims. Additionally Ramillo teaches administering oseltamivir and measuring expression of the elected gene set.
The claims are enabled to the extent of the specification in order to provide compact prosecution Ramillo is provided as it teaches the positive active steps of the claims.
Conclusion
No claims are allowable
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/SARAE L BAUSCH/Primary Examiner, Art Unit 1699
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