DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 90, 92-95, 97-102, 104-115 are pending in this application.
Applicant’s amendments to the claims filed 09/19/2025 and 03/09/2026 are acknowledged. The listing of the claims filed 03/09/2026 replaces all prior versions and listings of the claims.
Applicant’s amendment to the specification filed 09/19/2025 is acknowledged.
Applicant’s amendment to the drawings filed 09/19/2025 is acknowledged.
Applicant’s remarks filed on 09/19/2025 in response to the non-final rejection mailed on 03/21/2025 is acknowledged and has been fully considered.
The rejections of claim 103 are withdrawn in view of the cancelation of claim 103.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election
The elected subject matter is
Species of Group A) the polypeptide Ribosomal protein S6 kinase alpha-5, and
Species of Group B) the metabolite creatinine
elected with traverse in the reply filed 12/04/2024 is acknowledged.
Applicant’s election without traverse of
the species of the method of claim 90, further comprising assaying the biofluid sample for the polypeptide DNA repair protein XRCC1,
in the reply filed reply filed 03/09/2026 is acknowledged.
Claim 111 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made with traverse in the reply filed on 12/04/2024.
Claims 90, 92-95, 97-102, 104-110 and 112-115 are being examined on the merits only to the extent they read on the elected subject matter.
Objections to Specification
The objection to the specification is withdrawn in view of the amendments regarding the use of trademarks.
Objections to Drawings
The objection to the drawings is withdrawn in view of the amendment to distinctly label the multiple viewings of Figure 1 and to have the corresponding descriptions of each panel disclosed in the specification.
Claim Objections
The objection to claim 90 is withdrawn in view of the amendment to recite the steps (a), (b), (c) and (d), and the substeps (i) and (ii) without the use of a period.
The objection to claim 110 is withdrawn in view of the amendment to no longer recite alternatives that end with a period.
Claim Rejections - 35 USC § 112(b)
Claims 90, 92-95, 97-102, 104-110 and 112-115 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The instant rejection is maintained from a previous office action, any newly recited portions are necessitated by claim amendment.
Claim 90 (claims 92-95, 97-99, 112 and 114 dependent therefrom) and 100 (claims 101-102, 104-110, 113 and 115 dependent therefrom) are rejected for the recitation of the phrase “a subject who has CIS and is a rapid convertor to CDMS”, as the term "rapid" in is a relative term which renders the claim indefinite. Regarding the term, the instant specification discloses on p 8 that a “rapid converter” may be a subject who converts within 10 years of CIS occurring, while in one embodiment it is a subject who converts within 5 years of a CIS occurring, and preferably is a subject who converts from within 4 years of a CIS occurring. As such, the term "rapid" is not clearly defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 90 (claims 92-95, 97-99, 112 and 114 dependent therefrom) and 100 (claims 101-102, 104-110, 113 and 115 dependent therefrom) are indefinite for the recitation of the phrases
“(d)(i) predicting that the subject will convert when … the assayed concentration is decreased when compared to … a non-convertor reference standard; or … decreased … when compared to … a convertor reference standard”, and
“(d)(ii) predicting that the subject will not convert when … the assayed concentration is increased … when compared to … a non-convertor reference standard; or … increased … when compared to … a convertor reference standard”.
It is unclear how observing the same relative result compared to opposite reference standards can produce the same conclusion. Put another way, it is unclear how a convertor is determined by observing a decrease in target molecule concentration compared to both a convertor and a non-convertor standard, as the two standards are interpreted to be synonymous with positive and negative controls for carrying out the method. Similarly, it is unclear how a convertor is determined by observing and increase in target molecule concentration compared to both a convertor and a non-convertor standard, as the two standards are interpreted to be synonymous with positive and negative controls for carrying out the method.
Claims 93 and 104 are rejected for the recitation of the phrases “wherein the concentration of Ribosomal protein S6 kinase alpha-5 is determined indirectly by assessing gene expression by: Northern blot, quantitative reverse transcription PCR (RT-PCR), RNA sequencing, and/or transcriptomics”, as it is unclear how the concentration of protein is determined using techniques for assaying nucleic acids.
Claim 100 (claims 101-102, 104-110, 113 and 115 dependent therefrom) is rejected for the recitation of the phrase “a subject who has CIS and is a slow convertor to CDMS”, as the term "slow" in is a relative term which renders the claim indefinite. Regarding the term, the instant specification discloses on p 9 that a “slow converter” may be a subject who converts more than 10 years from CIS occurring, in one embodiment it is a subject who converts more than 5 years from a CIS occurring, and preferably is a subject who converts more than 4 years from a CIS occurring. As such, the term "slow" is not clearly defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Response to Remarks: beginning on page 26 of Applicants response to 112(b) rejections mailed 09/19/2025; Applicant in summary contends the terms “rapid convertor” and “slow convertor” would be understood by one of skill in the art and that the terms are defined in the specification on page 8, line 33 to page 9, line 7; Applicant further contends claims 93 and 104 have been amended to reflect that protein concentration is indirectly determined by the RNA-associated methods, and one of skill in the art would clearly understand how the concentration of the protein can be determined by these methods; Applicant further contends the definitions of convertor and non-convertor standards in claim 100 overcomes the rejection of record.
Applicants remarks are considered and found not convincing.
Regarding the relative terms “rapid” and “slow”, the rejection of record cites the same portion of the specification referred to by Applicant, which states a “rapid converter” may be a subject who converts within 10 years of CIS occurring, while in one embodiment it is a subject who converts within 5 years of a CIS occurring, and preferably is a subject who converts from within 4 years of a CIS occurring, and a “slow converter” may be a subject who converts more than 10 years from CIS occurring, in one embodiment it is a subject who converts more than 5 years from a CIS occurring, and preferably is a subject who converts more than 4 years from a CIS occurring. As such, the terms “rapid” and "slow" are not clearly defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Regarding the indirect determination of protein by RNA techniques, it is unclear how one of skill in the art would determine a concentration of protein by RNA sequencing, transcriptomics, RT-PCR, or Northern blot analysis, as these are each measurements of RNA. Furthermore, there is no requirement that the RNA being measured by these methods is mRNA, and even considering that only mRNA is being measured, there is no requirement that the mRNA is translated to protein.
Regarding the definitions of convertor and non-convertor standards, these definitions do not clarify how observing the same relative result compared to opposite reference standards can produce the same conclusion as stated in the rejection above.
Claim Rejections - 35 USC § 101
Claims 90, 92-95, 97-102, 104-109 and 112-115 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims below were evaluated using “Subject Matter Eligibility Test for Products and Processes” as shown in MPEP 2016 III.
The instant rejection is maintained from a previous office action, and any newly recited portion is necessitated by claim amendment.
Claims 90, 92-95, 98-99, 112 and 114:
Patent Eligibility Analysis Step 1: The claim is drawn to a process (method) which is one of the four statutory categories.
Patent Eligibility Analysis Step 2A Prong 1: The claims recite the abstract ideas of “measuring a concentration” in recited in step (b), “comparing … the measured concentration” in step (c), “performing a statistical analysis” in step (c), “predicting that the subject will convert from CIS to CMDS” by “comparing” two concentrations recited in step (d) of independent claim 90. In the broadest reasonable interpretation of the claim, “measuring” encompasses the mental action of counting, “comparing” encompasses the mental action of analyzing at least two data points, “performing a statistical analysis” encompasses the abstract idea of a mathematical concept, “predicting by comparing” encompasses the mental actions of analyzing at least two data points and interpreting said analysis to arrive at a conclusion. Accordingly, claims 90, 92-95, 98-99, 112 and 114 recite judicial exceptions.
Patent Eligibility Analysis Step 2A Prong 2: Claim 90 recites the additional element of “obtaining a biofluid sample” in step (a). However, the additional element encompasses data gathering needed to carry out the abstract idea. Data gathering does not impose any meaningful limitation on the abstract ideas, or how the abstract ideas are performed. Data gathering steps are not sufficient to integrate an abstract idea into a practical application (MPEP 2106.05(g)). Claim 90 also recites the additional element of “using a biological measurement instrument” to carry out the JE of measuring, which amounts to mere instructions to apply a judicial exception using a computer or other machinery merely as a tool to perform an existing process (MPEP 2106.05(f)). Claim 90 also recites the additional element of “performing [the JE] with a processor”, which amounts to mere instructions to apply a judicial exception using a computer or other machinery merely as a tool to perform an existing process (MPEP 2106.05(f)).
Claim 99 recites the additional element of recording the output of steps (b), (c) and (d) on a data-storage medium. However, under the broadest reasonable interpretation, “recording the output of steps” is drawn to writing down data values on paper, which is considered a mental activity, and therefore claim 99 recites an additional judicial exception. Alternatively, the additional element is considered to encompass data gathering and data outputting, which do not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering and outputting steps are not sufficient to integrate judicial exceptions into practical application (MPEP 2106.05(g)).
There are no additional elements recited in claims 92-95, 98, 112 and 114 beyond the judicial exception.
Patent Eligibility Analysis Step 2B: Achiron et al. (US 2010/0112568A1; cited on the IDS submitted 01/04/2022), Weiner et al. (WO 2013/055865 A1; cited on the IDS submitted 01/04/2022) and Powers et al. (J Proteome Res, 2016, 15:659; cited on the Form PTO-892 mailed 03/21/2025) all relate to methods of biomarker detection from samples derived from MS patients or patients with clinically isolated syndrome comprising blood samples [Weiner, regarding testing of monocytes in blood, p 19, para 2; Achiron, regarding the testing of blood cells derived from patient’s blood, para 0026] or urine samples which is considered to encompass a cell-free biofluid sample [Powers, abstract], wherein biomarkers were quantified using biological instruments [see Achiron paras 0102-0104; Weiner, p 64; Powers, p 660, col 2 final paragraph]. Additionally, while the methods of Achiron, Weiner and Powers do not explicitly recite the recording of output of the steps on a data-storage medium, the output of these steps is considered inherently to be recorded in order to carry out the respective disclosed methods, specifically in view of the multivariate analysis of Powers that is carried out on a computer, and therefore is considered to be performed by a processor [p 660, col 2, final paragraph] and statistical analysis of Weiner [p 20, beginning col 3]. In view of Achiron, Weiner and Powers, the additional element of “obtaining a biofluid sample” in step (a) of claim 90 and “recording the output of steps” in claim 99 are considered to be well-understood, routine and conventional activities previously known to the industry (MPEP 2106.05(d)), and therefore the judicial exception is recited without additional limitations amounting to significantly more than the exception. All of the signified additional elements to the judicial exception are considered to be required data collection steps of the judicial exception that are well-understood, routine and conventional, and, therefore, do not amount to significantly more than the judicial exception that is claimed.
Claims 101-102, 104-109, 113 and 115:
Patent Eligibility Analysis Step 1: The claim is drawn to a process (method) which is one of the four statutory categories.
Patent Eligibility Analysis Step 2A Prong 1: The claims recite the abstract ideas of “assaying the biofluid sample for a concentration” in step (b), “comparing the assayed concentrations” by “performing a statistical analysis” in step (c), and “predicting that the subject will convert from CIS to CMDS” and “predicting that the subject will not convert from CIS to CDMS” by “comparing” two concentrations of in step (d) of independent claim 100. In the broadest reasonable interpretation, “assaying the biofluid sample for a concentration” encompasses the mental action of measuring or counting the amount of a component of a sample, “comparing” encompasses the mental action of analyzing at least two data points, “performing a statistical analysis” encompasses the abstract idea of a mathematical concept, “predicting by comparing” encompasses the mental actions of analyzing at least two data points and interpreting said analysis to arrive at a conclusion. Accordingly, claims 101-102, 104-109, 113 and 115 recite judicial exceptions.
Patent Eligibility Analysis Step 2A Prong 2: Claim 100 recites the additional element of “obtaining a biofluid sample” in step (a). However, the additional element encompasses data gathering needed to carry out the abstract idea. Data gathering does not impose any meaningful limitation on the abstract ideas, or how the abstract ideas are performed. Data gathering steps are not sufficient to integrate an abstract idea into a practical application (MPEP 2106.05(g)). Claim 100 also recites the additional element of “using a biological measurement instrument” to carry out the JE of measuring, which amounts to mere instructions to apply a judicial exception using a computer or other machinery merely as a tool to perform an existing process (MPEP 2106.05(f)). Claim 100 also recites the additional element of “performing [the JE] with a processor”, which amounts to mere instructions to apply a judicial exception using a computer or other machinery merely as a tool to perform an existing process (MPEP 2106.05(f)).
Claim 108 recites the additional element of recording the output of steps (b), (c) and (d) on a data-storage medium. However, under the broadest reasonable interpretation, “recording the output of steps” encompasses writing down data values on paper, which is considered a mental activity, and therefore claim 108 recites an additional judicial exception. Alternatively, the additional element encompasses data gathering and data outputting, which do not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering and outputting steps are not sufficient to integrate judicial exceptions into practical application (MPEP 2106.05(g)).
There are no additional elements recited in claims 101-102, 104-107, 109, 113 and 115 beyond the judicial exception.
Patent Eligibility Analysis Step 2B: Achiron et al. (US 2010/0112568A1; cited on the IDS submitted 01/04/2022), Weiner et al. (WO 2013/055865 A1; cited on the IDS submitted 01/04/2022) and Powers et al. (J Proteome Res, 2016, 15:659; cited on the Form PTO-892 mailed 03/21/2025) all relate to methods of biomarker detection from samples derived from MS patients or patients with clinically isolated syndrome comprising blood samples [Weiner, regarding testing of monocytes in blood, p 19, para 2; Achiron, regarding the testing of blood cells derived from patient’s blood, para 0026] or urine samples which is considered to encompass a cell-free biofluid sample [Powers, abstract], wherein biomarkers were quantified using biological instruments [see Achiron paras 0102-0104; Weiner, p 64; Powers, p 660, col 2 final paragraph]. Additionally, while the methods of Achiron, Weiner and Powers do not explicitly recite the recording of output of the steps on a data-storage medium, the output of these steps is considered inherently to be recorded in order to carry out the respective disclosed methods, specifically in view of the multivariate analysis of Powers that is carried out on a computer, and therefore is considered to be performed by a processor [p 660, col 2, final paragraph] and statistical analysis of Weiner [p 20, beginning para 4; p 115, para 1]. In view of Achiron, Weiner and Powers, the additional element of “obtaining a biofluid sample” in step (a) of claim 100 and “recording the output of steps” in claim 108 are considered to be well-understood, routine and conventional activities previously known to the industry (MPEP 2106.05(d)), and therefore the judicial exception is recited without additional limitations amounting to significantly more than the exception. All of the signified additional elements to the judicial exception are considered to be required data collection steps of the judicial exception that are well-understood, routine and conventional, and, therefore, do not amount to significantly more than the judicial exception that is claimed.
As the instant claims recite judicial exceptions that are not integrated into practical application, and no elements that amount to significantly more than the judicial exception as recited, the claims were found not to be drawn to eligible subject matter under 35 U.S.C. 101.
Response to remarks: beginning on page 27 of Applicant’s response to 101 rejections filed 09/19/2025; Applicant in summary contends the claims do not recite any abstract ideas as none of the cited JEs in the rejection can be practically done in the human mind; Applicant further contends the claimed method establishes an improvement in the field based on the ability to provide early prediction of conversion from CIS to CDMS as well as the speed and prognosis of said conversion in view of the instant specification; Applicant further contends the additional elements in the claim render the invention significantly more than the JE as a result of providing technical improvements by way of the additional elements being non-conventional and providing the improvement for predicting a subject will convert from CIS to CDMS, and predicting a subject will not convert from CIS to CDMS; Applicant further contends the use of a biological instrument and performing of statistical analysis with a processor are significantly more than an abstract idea.
Applicant’s remarks are considered and found not convincing.
Regarding the assertion that the identified JEs of the rejection are not abstract ideas as they cannot be practically performed in the human mind, Applicant states “using a biological instrument to measure a concentration” and “comparing, by performing a statistical analysis with a processor” as recited in independent claims 90 and 100 are not capable of being carried out by the human mind. Applicant’s examples are not the identified JEs of the rejection, and therefore are not considered at Step 2A1. The identified JEs can be found in the rejection above, and corresponding to Applicants examples are “measuring”, “comparing”, and “performing statistical analysis”, which are drawn to mental activities as described above, and are considered capable of being carried out in the human mind. Applicant has offered no reasoning why a human mind cannot perform the activities of “measuring”, “comparing” and “performing statistical analysis”.
Regarding the assertion that the additional elements in the claim render the invention significantly more than the abstract idea, the additional elements cited by Applicant apply to two of the five identified JEs in each independent claim. These additional elements are identified and evaluated in Step 2A2, and are directed to mere data gathering required to carry out the abstract idea which does not impose any meaningful limitations on the abstract idea or how the abstract ideas are performed, or are mere instructions to apply a judicial exception using a computer or other machinery merely as a tool to perform an existing process, and therefore are not sufficient to integrate the abstract idea into practical application. The additional elements cited by Applicant of the use of a biological instrument and performing of statistical analysis with a processor are considered mere instructions to apply a judicial exception using a computer or other machinery merely as a tool to perform an existing process. Applicant’s assertion that the improved prediction of the method establishes the method as an improvement in the field amounts to an improvement in a JE as a result of another JE. For example the prediction is facilitated by the comparison, which is facilitated by the measuring, the comparing, and the math, all of which are JEs themselves, and the carrying out of these JEs improves the final JE. However, JEs cannot be a practical application of a JE as stated in MPEP 2106.04.II.A.2 “Because a judicial exception is not eligible subject matter, Bilski, 561 U.S. at 601, 95 USPQ2d at 1005-06 (quoting Chakrabarty, 447 U.S. at 309, 206 USPQ at 197 (1980)), if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application.”
Regarding the assertion that the invention establishes an improvement in the field based on the ability to provide early prediction of conversion from CIS to CDMS as well as the speed and prognosis of said conversion, and that said improvement is specifically recited in the claims as steps of predicting that a subject will convert from CIS to CDMS, and predicting a subject will not convert from CIS to CDMS, wherein this prediction is additionally non-conventional:
as stated above, the recited prediction is a JE, and a JE cannot provide integration or practical application of another JE. Step 2B requires examining only the additional elements, either alone or in combination with one another, for conventionality. An “inventive concept” is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself (Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966)). The limitations pointed to by Applicant are considered to recite a judicial exception as described above and are therefore not considered at Step 2B. As stated in the rejection above in Step 2B, the additional elements recited in the claims are considered to be well understood, routine and conventional.
Claim Rejections - 35 USC § 103
Claims 90, 93-95, 97-101, and 104-109 are rejected under 35 U.S.C. 103 as being unpatentable over Achiron et al. (US 2010/0112568A1; cited on the IDS submitted 01/04/2022; herein referred to as Achiron) in view of Weiner et al. (WO 2013/055865 A1; cited on the IDS submitted 01/04/2022; herein referred to as Weiner).
The instant rejection is maintained from a previous office action. Any newly recited portions are necessitated by claim amendment.
Claim 90 (claims 93-95, and 97-99 dependent therefrom) is drawn to a method of predicting conversion of a subject from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS), the method comprising:
obtaining a biofluid sample derived from the subject having, or suspected of having, CIS;
using a biological measurement instrument to measure a concentration of Ribosomal protein S6 kinase alpha-5 (R6SKA5) and/or creatinine in the sample;
comparing by performing a statistical analysis with a processor the measured concentration with the concentration of the R6SKA5 and/or creatinine, respectively, in a reference standard; and
(d)(i) predicting that the subject will convert from CIS to CDMS when:
the measured concentration is decreased when compared to the concentration in the reference standard when the reference standard is a non-convertor reference standard; or the measured concentration is decreased or the same when compared to the concentration in the reference standard when the reference standard is a convertor reference standard; and/or
(d)(ii) predicting that the subject will not convert from CIS to CDMS when:
the measured concentration is increased or the same when compared to the concentration in the reference standard when the reference standard is a non-convertor reference standard; or the measured concentration is increased or the same when compared to the concentration in the reference standard when the reference standard is a convertor reference standard; or
wherein the convertor reference standard corresponds to a subject who has CIS and is a rapid convertor to CDMS or that has MS.
The instant specification does not specifically define the term “CIS”, but gives examples that it is “an initial neurological attack” [p 1] and “may refer to a first episode of neurologic symptoms that lasts for at least 24 hours and that is caused by inflammation and/or demyelination in the brain of the subject” [p 3].
The instant specification does not clearly define the terms “rapid convertor” and “slow convertor”, but provides the following examples:
“A ‘rapid convertor’ (used synonymously with ‘fast convertor’ herein) may be a subject who converts from CIS to CDMS within 10 years of CIS occurring. In one embodiment a ‘rapid convertor’ is a subject who converts from CIS to CDMS within 5 years of CIS occurring. Preferably, a ‘rapid convertor’ is a subject who converts from CIS to CDMS within 4 years of CIS occurring” [p 8-9],
and
“A ‘slow convertor’ may be a subject who converts from CIS to CDMS in more than 10 years of CIS occurring. In one embodiment a ‘slow convertor’ is a subject who converts from CIS to CDMS in more than 5 years of CIS occurring. Preferably, a ‘slow convertor’ is a subject who converts from CIS to CDMS in more than 4 years of CIS occurring” [p 9].
In view of the specification, and for the sake of the examination, the term “rapid convertor” is being interpreted as a subject who converts from CIS to CDMS within 10 years of CIS occurring, and the term “slow convertor” is being interpreted as a subject who converts from CIS to CDMS more than 10 years from CIS occurring.
Achiron relates to methods for diagnosis of MS in probable MS subjects [title].
Regarding claim 90, Achiron discloses the differential expression of markers in subjects diagnosed with probable MS which further develop the definite diagnosis of MS [para 0001], and describes a method for identifying a patient with CIS at high risk for developing MS by detecting the level of expression of a marker gene and comparing the level of expression to a control [claim 1] which is considered to correspond to the limitations in step (a) of claim 90 as determining the expression of a marker gene is interpreted to encompass obtaining a biofluid sample from a patient, the limitations in step (c) of claim 90 of comparing the measured concentration with a standard, and the limitations in step (d) of claim 90 of predicting whether or not subject will convert to CDMS based on the comparison of the measured biomarker compared to a control. Additionally the determination of biomarker levels by Achiron comprised the detection of labeled nucleotides generated from extracted RNA [para 0102-0104], which corresponds to the limitations in step (b) of claim 90 of measuring the concentration of a protein with a biological instrument.
Achiron does not teach measuring the concentrations of the Ribosomal protein S6 kinase alpha-5 (RPS6KA5) or creatinine, the comparison to non-convertor and convertor reference standards, and the carrying out of statistical analysis with a processor.
Weiner relates to neurodegenerative disorders (NDD) [title] and discloses methods for diagnosing NDD in a subject, identifying subject at risk of developing NDD, wherein the NDD is MS [abstract].
Regarding claims 90, Weiner discloses a method for diagnosing and identifying subjects at risk for NDD by determining the level of inflammatory markers on monocytes or in CSF [abstract], wherein RPS6KA5 is shown to be an inflammatory marker that is decreased in monocytes from patients having NDD relative to healthy controls [Table 20], which corresponds to the limitations of measuring concentrations of RPSKA5 and comparing them to a control, which are interpreted to correspond to the limitations in steps (b), (c) and (d) of claim 90. Weiner further discloses that healthy controls come from a subject that does not present with two or more symptoms of a neurodegenerative disorder, a subject that has not been diagnosed with a neurodegenerative disorder, and/or a subject that has no family history of neurodegenerative disease [p 17, para 2], which is considered to encompass the non-convertor reference standard of a subject that has CIS but does not have multiple sclerosis (MS) as recited in the claims. Weiner additionally discloses the calculation of statistical significance by importing data into MetaCore [p 115, para 1; and Figure descriptions beginning on p 20, para 4], which is considered to correspond to the limitations of part (c) regarding performing statistical analysis with a processor.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine Achiron and Weiner to modify the method of Achiron by detecting the polypeptide RPS6KA5, as taught by Weiner, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the method of Achiron by detecting the polypeptide RPS6KA5, because Weiner teaches that methods for identifying subject at risk of developing MS comprising detecting differential levels of the polypeptide RPS6KA5. One of ordinary skill in the art would have had a reasonable expectation of success because both Achiron and Weiner relate to methods for identifying and diagnosing MS in probable MS subjects.
Regarding claim 93, Achiron discloses the use of Northern blot analysis and RT-PCR to characterize expression [para 0063].
Regarding claim 94, the claim limits the assaying of creatinine concentration to be carried out by NMR, MS, HPLC-UV and/or IR spectrometry, but does not limit the method of claim 90 to assay the concentration of creatinine. Therefore the method recited in claim 94 still encompasses the alternatives of claim 90 of measuring a concentration of R6SKA5, a concentration of creatinine, or a concentration of both R6SKA5 and creatinine. Therefore the teachings used to reject claim 90 are also used for claim 94.
Regarding claim 95, Achiron discloses the testing of samples comprising blood cells [claim 17], which is considered to correspond to the biofluid sample being blood.
Regarding claim 97, Achiron discloses upon the determination that one might develop definite MS, the subject can be treated with suitable therapeutics to prevent deterioration of clinical symptoms and can increase the chance of achieving cure and remission of symptoms [para 0079], which is interpreted to correspond to the delay of conversion.
Regarding claim 98, the claim limits the convertor reference standard to be from a subject that has relapsing-remitting multiple sclerosis (RRMS), but does not limit the method of claim 90 to compare to the convertor reference standard. Therefore the method recited in claim 98 still encompasses the alternatives of claim 90 including the comparison to a non-convertor reference standard. Therefore the teachings used to reject claim 90 are also used for claim 98.
Regarding claim 99, Achiron and Weiner discloses the combined method described in the rejections of claim 90 above, which do not explicitly recite the recording of output of the steps on a data-storage medium. However, as the output of these steps is considered inherently to be recorded in order to carry out the disclosed methods, under the broadest reasonable interpretation the output of these steps is recorded by hand on paper, wherein paper is considered to be encompassed by a data-storage medium. As such, the combined method of Achiron and Weiner satisfies the claim limitations. Considering an alternative interpretation that data-storage medium is intended to mean a computer-readable medium, according to MPEP 2144.04.III, it is obvious to automate a manual activity, wherein broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art.
Regarding claim 100, Achiron discloses the differential expression of markers in subjects diagnosed with probable MS which further develop the definite diagnosis of MS [para 0001], and describes a method for identifying a patient with CIS at high risk for developing MS by detecting the level of expression of a marker gene and comparing the level of expression to a control [claim 1] which is considered to correspond to the limitations in step (a) of claim 100 as determining the expression of a marker gene is interpreted to encompass obtaining a biofluid sample from a patient, the limitations in step (c) of claim 100 of comparing the measured concentration with a standard, and the limitations in step (d) of claim 100 of predicting whether or not subject will convert to CDMS based on the comparison of the measured biomarker compared to a. Additionally the determination of biomarker levels by Achiron comprised the detection of labeled nucleotides generated from extracted RNA [para 0102-0104], which corresponds to the limitations in step (b) of claim 100 of measuring the concentration of a protein with a biological instrument. Weiner discloses a method for diagnosing and identifying subjects at risk for NDD by determining the level of inflammatory markers on monocytes or in CSF [abstract], wherein RPS6KA5 is shown to be an inflammatory marker that is decreased in monocytes from patients having NDD relative to healthy controls [Table 20], which corresponds to the limitations of measuring concentrations of RPSKA5 and comparing them to a control, which are interpreted to correspond to the limitations in steps (b), (c) and (d) of claim 100. Weiner further discloses that healthy controls come from a subject that does not present with two or more symptoms of a neurodegenerative disorder, a subject that has not been diagnosed with a neurodegenerative disorder, and/or a subject that has no family history of neurodegenerative disease [p 17, para 2], which is considered to encompass the non-convertor reference standard of a subject that has CIS but does not have multiple sclerosis (MS) as recited in the claims. Weiner additionally discloses the calculation of statistical significance by importing data into MetaCore [p 115, para 1; and Figure descriptions beginning on p 20, para 4], which is considered to correspond to the limitations of step (c) of claim 100 regarding performing statistical analysis with a processor.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine Achiron and Weiner to modify the method of Achiron by detecting the polypeptide RPS6KA5, as taught by Weiner, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the method of Achiron by detecting the polypeptide RPS6KA5, because Weiner teaches that methods for identifying subject at risk of developing MS comprising detecting differential levels of the polypeptide RPS6KA5. One of ordinary skill in the art would have had a reasonable expectation of success because both Achiron and Weiner relate to methods for identifying and diagnosing MS in probable MS subjects.
Regarding claim 101, Achiron discloses the method wherein the differential expression of a marker indicates a high probability of the subject to develop definite MS within a period of about 2 years [para 0068].
Regarding claim 104, Achiron discloses the use of Northern blot analysis and RT-PCR to characterize expression [para 0063].
Regarding claim 105, the claim limits the determination of creatinine concentration to be carried out by NMR, MS, HPLC-UV and/or IR spectrometry, but does not limit the method of claim 90 to determine the concentration of creatinine. Therefore the method recited in claim 94 still encompasses the alternatives of claim 100 of measuring a concentration of R6SKA5, a concentration of creatinine, or a concentration of both R6SKA5 and creatinine. Therefore the teachings used to reject claim 100 are also used for claim 105.
Regarding claim 106, Achiron discloses the testing of samples comprising blood cells [claim 17], which is considered to correspond to the biofluid sample being blood.
Regarding claim 107, the claim limits the convertor reference standard to be from a subject that has relapsing-remitting multiple sclerosis (RRMS), but does not limit the method of claim 100 to compare to the convertor reference standard. Therefore the method recited in claim 107 still encompasses the alternatives of claim 90 including the comparison to a non-convertor reference standard. Therefore the teachings used to reject claim 100 are also used for claim 107.
Regarding claim 108, Achiron and Weiner discloses the combined method described in the rejections of claim 100 above, which do not explicitly recite the recording of output of the steps on a data-storage medium. However, as the output of these steps is considered inherently to be recorded in order to carry out the disclosed methods, under the broadest reasonable interpretation the output of these steps is recorded by hand on paper, wherein paper is considered to be encompassed by a data-storage medium. As such, the combined method of Achiron and Weiner satisfies the claim limitations. Considering an alternative interpretation that data-storage medium is intended to mean a computer-readable medium, according to MPEP 2144.04.III, it is obvious to automate a manual activity, wherein broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art.
Regarding claim 109, Achiron discloses upon the determination that one might develop definite MS, the subject can be treated with suitable therapeutics to prevent deterioration of clinical symptoms and can increase the chance of achieving cure and remission of symptoms [para 0079], which is interpreted to correspond to the delay of conversion.
Therefore, the invention of claims 90, 93-95, 97-101, and 104-109 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 92 and 102 are newly rejected under 35 U.S.C. 103 as being unpatentable over Achiron and Weiner as applied to claims 90, 93-95, 97-101, and 104-109 above, and further in view of Karahalil et al. (Clin Neurol Neurosurg, 2015, 138:288; cited on the attached Form PTO-892; herein referred to as Karahalil).
The instant claim is newly stated and necessitated by claim amendment.
Claim 92 is drawn to the method of claim 90, further comprising assaying the biofluid sample for a concentration of the DNA Repair XRCC1 polypeptide.
Claim 102 is drawn to the method of claim 100, wherein step (b) further comprises further assaying the biofluid sample for a concentration of the DNA Repair XRCC1 polypeptide.
For the sake of compact prosecution, claim 92 is being interpreted as modifying step (b) of claim 90 to further comprise assaying the biofluid sample for a concentration of the DNA Repair XRCC1 polypeptide.
The teachings of Achiron and Weiner as applied to 90, 93-95, 97-101, and 104-109 are discussed above. These references do not teach assaying the biofluid sample for a concentration of the DNA Repair XRCC1 polypeptide.
Karahalil relates to the impact of repair gene polymorphisms and the levels of serum ROS in the susceptibility to multiple sclerosis [title] and discusses the possible relationship between the defect in DNA repair enzymes and MS via exposure to resulting oxidative stress [abstract].
Regarding claims 92 (dependent from claim 90) and 102 (dependent from claim 100), Karahalil teaches a method of assessing the association between oxidative stress, detoxification and DNA repair gene polymorphisms [p 288, col 2, final paragraph] by quantifying said genes from blood and serum samples from of MS patients [p 289, col 2, para 1], wherein one of the genes assayed was XRCC1 [p 289, col 2, final paragraph]. Karahalil teaches that XRCC1 gene polymorphisms show no impact on MS risk, while previous studies have shown such polymorphisms have a protective effect on the risk of MS, indicating the complex relationship between the gene and MS risk, and teaches smoking increased the risk of patients having these polymorphisms [p 292, col 1, final paragraph to col 2, first paragraph].
In view of Karahalil, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Achiron and Weiner by assaying XRCC1 concentrations, as taught by Karahalil, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Achiron and Weiner by assaying XRCC1 concentrations, because Karahalil teaches the possible relationship between the defect in DNA repair enzymes and MS via exposure to resulting oxidative stress and shows increased MS risk in patients with XRCC1 genotypes. One of ordinary skill in the art would have had a reasonable expectation of success because Achiron, Weiner and Karahalil relate to methods for identifying biomarkers to distinguish probable MS subjects.
Therefore, the invention of claims 92 and 102 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 110 is rejected under 35 U.S.C. 103 as being unpatentable over Achiron and Weiner as applied to claims 90, 93-95, 97-101, and 104-109 above, and further in view of Powers et al. (J Proteome Res, 2016, 15:659; reference is made to both the article and the Supplemental Information section, both cited on the Form PTO-892 mailed 03/21/2025; herein referred to as Powers).
The instant rejection is maintained from a previous office action. Any newly recited portion is necessitated by claim amendment.
Claim 110 is drawn to the method of claim 109, wherein the therapeutic comprises: alemtuzumab, beta interferons, cladribine, dimethyl fumarate, fingolimod, glatiramer acetate, natalizumab, teriflunomide, a hematopoietic stem cell, and/or a progenitor cell.
The teachings of Achiron and Weiner as applied to 90, 93-95, 97-101, 104-109 are discussed above. These references do not teach the therapeutic comprises: alemtuzumab, beta interferons, cladribine, dimethyl fumarate, fingolimod, glatiramer acetate, natalizumab, teriflunomide, a hematopoietic stem cell, and/or a progenitor cell.
Powers relates to the urinary metabolic signature for MS [title], and discloses that clinical diagnoses routinely rely on urine samples and represents an under-investigated source of biomarkers for MS [abstract], as the analysis of urine samples to obtain a metabolic profile has the advantages of being a rapid, easy, inexpensive and noninvasive sample collection procedure [p 659, col 2, para 2].
Regarding claim 110, Powers discloses interferon β-b1 as a therapeutic for the treatment of patients with MS [p 660, col 2, para 1], indicating this as a therapeutic for the treatment of MS.
In view of Powers, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Achiron and Weiner by treating patients with interferon, as taught by Powers, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Achiron and Weiner by treating patients with interferon, because Powers teaches methods of clinical diagnoses of MS comprising analysis of biosamples derived from MS patients that are chronically treated with interferon. One of ordinary skill in the art would have had a reasonable expectation of success because Achiron, Weiner and Powers relate to methods for identifying biomarkers to distinguish probable MS subjects.
Therefore, the invention of claim 110 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 112-113 are newly rejected under 35 U.S.C. 103 as being unpatentable over Achiron and Weiner as applied to claims 90, 93-95, 97-101, and 104-109 above, and further in view of UniProt Accession No. A0A2R9BP98_PANPA (3 pages, 11 Dec 2019; cited on the attached Form PTO-892; herein referred to as UNI1).
The instant claim is newly stated and necessitated by claim amendment.
Claim 112 is drawn to the method of claim 90 wherein the RS6KA5 comprises a polypeptide sequence having at least 90% sequence identity to SEQ ID NO: 1, or a polypeptide sequence comprising SEQ ID NO: 1.
Claim 113 is drawn to the method of claim 100 wherein the RS6KA5 comprises a polypeptide sequence having at least 90% sequence identity to SEQ ID NO: 1, or a polypeptide sequence comprising SEQ ID NO: 1.
The teachings of Achiron and Weiner as applied to 90, 93-95, 97-101, and 104-109 are discussed above. These references do not teach the sequence limitations of RS6KA5.
Regarding claims 112-113, UNI1 discloses an RS6KA5 polypeptide that shares 100% sequence identity with SEQ ID NO: 1 [see Appendix A].
In view of UNI1, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Achiron and Weiner by replacing the assaying of RS6KA5 of Achiron and Weiner with that of the RS6KA5 of UNI1 to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the RS6KA5 of Achiron and Weiner and the RS6KA5 of UNI1 are both RS6KA5 polypeptides, and as such both are capable of being incorporated into such methods as disclosed by Achiron and Weiner. Thus, it would have been obvious to one of ordinary skill in the art to replace the RS6KA5 of Achiron and Weiner with the RS6KA5 of UNI1, as one of ordinary skill in the art would have been capable of carrying out such a substitution with a reasonable expectation of success because Weiner discloses a method of predicting MS conversion by assaying polypeptides such as RS6KA5 and UNI1 discloses a RS6KA5 polypeptide.
Therefore, the invention of claims 112-113 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 114-115 are newly rejected under 35 U.S.C. 103 as being unpatentable over Achiron and Weiner as applied to claims 90, 93-95, 97-101, and 104-109 above, and further in view of Sheinerman et al. (Front Cell Neurosci, 2013, 7:1; cited on the attached Form PTO-892; herein referred to as Sheinerman).
The instant claim is newly stated and necessitated by claim amendment.
Claim 114 is drawn to the method of claim 90 wherein the sample is a cell-free biofluid sample.
Claim 115 is drawn to the method of claim 100 wherein the sample is a cell-free biofluid sample.
The teachings of Achiron and Weiner as applied to 90, 93-95, 97-101, and 104-109 are discussed above. These references do not teach the sample is a cell-free biofluid sample.
Sheinerman relates to circulating cell-free microRNA as biomarkers for screening, diagnosis, and monitoring of neurodegenerative diseases and other neurologic pathologies [title].
Regarding claims 114-115, Sheinerman teaches that miRNA in CSF or the bloodstream has the potential use for diagnosing MS [p 6, col 2, para 2], wherein the diagnostic taught by Sheinerman is considered to comprise identification and quantification of RNA from cell-free samples.
In view of Sheinerman, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Achiron and Weiner by assaying cell-free biosamples, as taught by Sheinerman, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Achiron and Weiner by assaying cell-free biosamples, because Sheinerman teaches the analysis of RNA from cell-free samples has the potential to be used for diagnosing MS. One of ordinary skill in the art would have had a reasonable expectation of success because Achiron, Weiner and Sheinerman relate to methods for identifying biomarkers to distinguish MS subjects.
Therefore, the invention of claims 114-115 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to Remarks: beginning on page 34 of Applicant’s response to rejections under 35 USC 103 mailed 09/19/2025;
Applicant in summary contends the claimed method has a surprising effect of allowing the highly sensitive, accurate and/or specific prediction as to whether a subject will convert from CIS to CDMS according to the specification at page 2, lines 11-15, specifically Tables 1-2; Applicant further contends Achiron does not teach a method for predicting conversion to CDMS, and Achiron merely provides data for differential expression of markers compared to healthy controls; Applicant further contends Achiron teaches away from using RS6KA5 in the manner corresponding to the instant claims by showing RS6KA5 increases in subjects with developed MS compared to healthy controls [see Table 2] contrary to the instant claims that recite conversion to CDMS occurs when RS6KA5 is decreased compared to both non-convertor and convertor reference standards; Applicant further contends that (i) Weiner does not mention CDMS, (ii) Weiner compares to healthy controls similar to Achiron and it is impossible to determine whether the biomarkers of Weiner could be used for predicting conversion to CDMS, (iii) there is no indication for which biomarker from Table 20 of Weiner to choose to predict the conversion of CDMS, (iv) Weiner does not disclose the non-convertor reference standard, and (v) Weiner does not teach or suggest measuring metabolites;
Applicants remarks are considered and found not convincing.
Regarding the assertion that Achiron does not teach a method for predicting conversion to CDMS and merely provides data for differential expression of markers compared to healthy controls, the teachings of Achiron are described in detail in the rejection above. Briefly, Achiron teaches the differential expression of markers in subjects diagnosed with probable MS which further develop the definite diagnosis of MS, which is considered to correspond to predicting whether a subject with CIS will convert to CDMS by comparing the amounts of biomarkers in subjects compared with controls.
Regarding the assertion that Achiron teaches away from using RS6KA5 in the manner corresponding to the instant claims by showing RS6KA5 increases in subjects with developed MS compared to healthy controls [see Table 2], Achiron does not teach away from any subject matter as Achiron does not criticize, discredit, or otherwise discourage carrying out the method of predicting whether a subject will convert to CDMS via comparison of biomarker expression to controls (MPEP 2143.01.I). The data of Achiron presented in Table 2 cited by applicant is of differential gene expression, and is annotated qualitatively as either an upregulation or a downregulation of markers compared to controls. The degree of upregulation of targets is not disclosed by Achiron, and the upregulation is a measurement of RNA taken from samples [see paras 0102-0104]. As pointed out by Applicant, at the top of page 35 of the remarks, Achiron does not compare polypeptide or metabolite concentrations, and also does not compare to the same convertor or non-convertor standards recited in the claims. As such, the rejection above relies on Achiron’s teaching of the overall method of predicting whether a subject will convert to CDMS via comparison of biomarker expression to controls, as MPEP 2123.II states that disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments, and MPEP 2123.I states literature of the art is relevant for all it contains.
Regarding the assertion that (i) Weiner does not mention CDMS, (ii) Weiner compares to healthy controls similar to Achiron and it is impossible to determine whether the biomarkers of Weiner could be used for predicting conversion to CDMS, (iii) there is no indication for which biomarker from Table 20 of Weiner to choose to predict the conversion of CDMS, (iv) Weiner does not disclose the non-convertor reference standard, and (v) Weiner does not teach or suggest measuring metabolites:
The teachings of Weiner are described in the rejection above.
Regarding (i), Weiner teaches a method for diagnosing and identifying subjects at risk for NDD by determining the level of inflammatory markers compared to controls, wherein MS is considered an NDD by Weiner and is therefore considered to correspond to CDMS, and wherein RPS6KA5 is shown to be an inflammatory marker that is decreased in monocytes from patients having NDD relative to healthy controls.
Regarding (ii), the healthy controls of Weiner are subjects that do not present with two or more symptoms of a neurodegenerative disorder (e.g., CDMS), a subject that has not been diagnosed with a neurodegenerative disorder (e.g., CDMS), and/or a subject that has no family history of neurodegenerative disease (e.g., CDMS). As the instant specification does not specifically define but describes CIS as someone who has an initial neurological attack [p 1, 3rd paragraph], the control of Weiner that does not present 2 or more symptoms of MS is considered to be encompassed by a non-convertor reference standard of a subject that has CIS but does not have multiple sclerosis (MS) as recited in the claims. As Weiner discloses the changes in these biomarkers for those who have a NDD (e.g., CDMS) compared to controls corresponding to non-convertor standards, Weiner suggests assaying said biomarkers can be useful when combined with the general method of Achiron, and therefore considering the preponderance of evidence of the prior art it would have been obvious to combine Weiner and Achiron.
Regarding (iii) and (iv), there is no requirement for one of ordinary skill in the art to choose a single biomarker from the table of Weiner to perform the claimed method, as claim 90 and 100 recite “the method comprises” in open language followed by enumerated steps. Therefore the method can be interpreted to include choosing multiple biomarkers, such as, for example, all of the biomarkers disclosed by Weiner, and in doing so would be carrying out the claimed method as set forth in the rejection above.
Regarding (v), the claims do recite the measuring of metabolites.
Regarding the assertion that the claimed method has a surprising effect of allowing the highly sensitive, accurate and/or specific prediction as to whether a subject will convert from CIS to CDMS according to the specification at page 2, lines 11-15, specifically Tables 1-3, Applicant’s response is being interpreted as an allegation of unexpected results. Applicant cites page 2, lines 11-15 of the instant specification:
“The methods of the invention allow for improved diagnosis of MS per se, CIS, and/or CDMS, as well as determining prognosis of MS. In particular, the methods of the invention allow determination of conversion of a subject from CIS to CDMS (e.g. within 4 years). Advantageously, the methods of the invention are particularly accurate and/or sensitive and/or specific” [page 2, lines 11-15].
which reiterates Applicant’s remarks, and Tables 1-3, which correspond to protein biomarkers identified from an unspecified experiment [Table 1, p 115], CSF NMR metabolomics hits identified from an unspecified experiment [Table 2, p 121], and serum NMR metabolomics hits from an unspecified experiment [Table 3, p 122]. The experiment producing said data is considered to be that of Example I [p 115] which is described as metabolomics analysis able to diagnose CDMS and CIS with specified accuracy values, which is presumed to include the assays beginning on p 112 comprising obtaining biosamples from CDMS patients, CIS patients, and non-MS control patients, the samples comprising CSF, plasma and serum, and the techniques involving NMR [p 113] and multi-omics disclosed to be proteomics [p 112, middle].
MPEP 716.02(b).I states the burden is on applicant to establish the results are unexpected and significant, and that the differences in results are in fact unexpected and unobvious in both statistical and practical significance. In view of the teachings of Weiner and Achiron in the rejection above, Applicant has not satisfied the requirements of 716.02(b).I.
MPEP 716.02(e) states unexpected results must be compared with the closest prior art. As Applicant not compared the data to any prior art, Applicant has not satisfied the requirements of 716.02(e).
MPEP 716.02(d) states unexpected results must be commensurate in scope with the claimed invention. As the results proffered are presumed to be from the methods disclosed beginning at p 112 of the instant specification, these results are not commensurate in scope with the claimed invention which encompasses the obtaining of all types of biofluid samples and the use of all biological measurement instruments to measure the concentrations of RS6KA5 and/or creatinine. Furthermore, the data proffered does not address any prediction of conversion or non-conversion to CDMS, which is a required step recited in the claimed method. Therefore Applicant has not satisfied the requirements of 716.02(d).
For these reasons, Applicant’s allegations of unexpected results are considered insufficient to rebut a prima facie case of obviousness.
Conclusion
Status of the Application:
Claims 90, 92-95, 97-102, 104-115 are pending.
Claim 111 is withdrawn.
Claims 90, 92-95, 97-102, 104-110 and 112-115 are rejected.
No claim is in condition for allowance.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH SPANGLER whose telephone number is (571)270-0314. The examiner can normally be reached M-F 7:30 am - 4:30 pm.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656
APPENDIX A
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Sequence alignment of SEQ ID NO: 1 with UniProt Accession No. A0A2R9BP98_PANPA.
Prosecution Insights