DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. This action is in response to the papers filed March 12, 2026. Applicant’s remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. Any new grounds of rejection presented in this Office Action are necessitated by Applicant's amendments. Any rejections or objections not reiterated herein have been withdrawn. This action is made FINAL.
Applicant's election with traverse of Group I, the combination of miR-100 and S100A8, and administering the selected subject Losmapimod or other selective inhibitor of p38a/3 mitogen-activated protein kinases, antisense oligonucleotides that reduce DUX4 expression, or gene therapy, such as administration of miRNAs directed against DUX4 is reiterated for the record.
Claims 1, 44-62 are currently pending.
Claims 49, and 56-62 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected subject matter (a nonelected invention or nonelected species), there being no allowable generic or linking claim.
Applicants are reminded that for any amendment being filed in response to a restriction or election of species requirement and any subsequent amendment, any claims which are non-elected must have the status identifier (withdrawn). In response to this Office Action Applicants should indicate the current status of each claim.
Claims 1, 44-48, and 50-55 have been examined to the extent that the claims read on the elected biomarkers (miR-100 and S100A8). The additionally recited biomarkers have been withdrawn from consideration as being directed to a non-elected invention. Prior to allowance of the claim, any nonelected subject matter that is not rejoined with any allowed elected subject matter will be required to be removed from the claims.
Duplicate Claim Warning
3. Applicant is advised that should claim 51 be found allowable, claims 52 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Objections
4. Claim 45 is objected to because of the following informalities: the claims recites the following limitation twice in a row “detecting at least one”. Appropriate correction is required.
Claim Rejections - 35 USC § 101
5. 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, 44-48, 50-53 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims recite a judicial exception that is not integrated into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim analysis is set forth below.
Step 1: The claims are directed to the statutory category of a process.
Step 2A, prong one: Evaluate Whether the Claim Recites a Judicial Exception
The instant claims recite abstract ideas.
The claims recite the following limitations:
-A method for detecting or monitoring FSHD (clms 1, 50);
-comparing quantity of the at least one biomarker in the subject to a control value (clm 1);
-wherein the subject is identified as having FSHD when miR-100 is increased compared to the control value (clm 1);
-wherein the subject is identified as having FSDH when S100A8 is increased compared to the control value (clm 1);
-selecting a subject with FSHD or at risk of FSDH (clm 1); and
wherein the subject is identified as having severe FSHD miR-100 is increased compared to the control value (clm 50).
The broadest reasonable interpretation of these limitations is that they fall within the mental process groupings of abstract ideas because they cover concepts performed in the human mind, including observation, evaluation, judgment, and opinion.
For examples the steps of detecting/monitoring/identifying/selecting could all be accomplished by thinking about the level of the biomarkers. Additionally the comparing steps could be accomplished by reading a laboratory report and thinking about whether the level of the biomarkers is increased or decreased.
The instant claims recite a law of nature.
The claims recite a correlation between biomarkers (miR-100 and S100A8) and FSHD. This type of correlation is a consequence of natural processes, similar to the naturally occurring correlation found to be a law of nature by the Supreme Court in Mayo.
Step 2A, prong two: Evaluate Whether the Judicial Exception Is Integrated Into a Practical Application
The claims do NOT recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). 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 an 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 a step of “treating the subject for FSHD”. It is noted that 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. However the treatment or prophylaxis limitation must be “particular”, i.e., specifically identified so that it does not encompass all applications of the judicial exceptions. Here the “treating” step is not particular, and is instead merely instructions to “apply” the exception in a generic way.
In addition to the judicial exceptions the claims recite steps of collecting a sample and detecting miRNA and protein biomarkers in the sample. The steps 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.
Step 2B: Evaluate Whether the Claim Provides an Inventive Concept
In addition to the judicial exceptions the claims recite steps of collecting a sample and detecting miRNA and protein biomarkers. These steps do not amount to significantly more because they simply append well understood, routine, and conventional activities previously known in the art, specified at a high level of generality, to the judicial exceptions.
The steps are recited at a high level of generality. Collecting a sample in order to perform tests is well understood, routine, and conventional activity for those in the field of diagnostics. Detecting miRNA and protein biomarkers in a sample merely instructs a scientist to use any detection technique. The claim does not require the use of any particular non-conventional reagents. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine, and conventional activities engaged in by scientists prior to applicants invention and at the time the application was filed.
The prior art also demonstrates the well understood, routine, conventional nature of additional elements because it teaches that the additional elements are well known or commercially available. For example see the prior art of Statland (Journal of Neuromuscular Diseases 1 (2014) 181-190) and Matsuzaka (Environ Health Prev Med (2014) 19:452-458) cited in the prior OA.
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For the reasons set forth above the claims are not directed to patent eligible subject matter.
Response To Arguments
6. In the response the Applicants traversed the rejection under 35 USC 101. The Applicants argue that both the diagnosis of FSHD and its treatment represent practical applications. Moreover, the claims now require a concrete treatment step that integrates the FSHD diagnosing steps of claim 1 with treatment steps for FSHD. This step is particular to treatment of a patient diagnosed with FSHD by the preceding steps. It does not encompass all possible treatments based on detection of elevated or depressed biomarker levels. This treatment step is not optional and the claims do not broadly encompass situations where the "treating" does not occur.
This argument has been fully considered but is not persuasive. The claims encompass identifying subjects with FSHD based on the level of a miRNA and protein biomarker in a sample. The identifying step cannot be relied upon to provide integration because it is a judicial exception itself. Claim 1 as amended recites a step of “treating the subject for FSHD”. It is noted that 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. However the treatment or prophylaxis limitation must be “particular”, i.e., specifically identified so that it does not encompass all applications of the judicial exceptions. Here the “treating” step is not particular, and is instead merely instructions to “apply” the exception in a generic way. Thus the claims do not recite any steps/elements in addition the judicial exceptions that provide integration into a practical application and the rejection is maintained.
Claim Rejections - 35 USC § 112(b)
7. 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 51-53 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.
Claims 51-53 are rejected over the recitation of the phrase “the at least one biomarker”. It is noted that claim 1 refers to a “nucleic acid biomarker”, a “protein biomarker”, and “other biomarker”. Therefore it is unclear if the phrase “the at least one biomarker” refers to each of the three biomarker types, only two of the biomarker types, or a single biomarker type. Clarification is required.
Claim Rejections - 35 USC § 112(a)
8. 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.
9. Claim 54 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a Written Description rejection.
Claim 54 requires administering to the selected subject a selective inhibitor of p38a/3 mitogen-activated protein kinases.
The claim encompasses administering treatments that have not been defined in terms of their complete structure or any other relevant identifying characteristics.
The specification teaches the following (numbering with respect to the PG-Pub)
[0098] Targeted treatments such as those which reduce DUX4 expression, levels, or toxicity and gene therapy may also be used, such as administration of losmapimod a p38 mitogen-activated protein kinase inhibitor or other such inhibitors which inhibit p38alpha/beta MAPK-mediated signaling. Gene or stem cell therapies may also be employed.
The specification provides written description for losmapimod.
However the specification does not provide written description for selective inhibitors of p38a/3 mitogen-activated protein kinases. The breadth of the claims encompasses treatments which the present inventors were not in the possession of, or which were not known to the inventors. The instant disclosure does not allow one of skill in the art to visualize or recognize the structure of these treatments.
For these reasons claim 54 fails to meet the written description requirement because the claims encompass a significantly large genus of treatments which are not adequately described in the specification.
Response To Arguments
10. In the response the Applicants traversed the rejection under 35 USC 112(a)-Written Description. The Applicants argue that the claims as amended no longer read on "ANY antisense oligonucleotides".
The amendments have been fully considered. The rejection has been modified to include newly presented claim 54. This claim lacks written description for the reasons cited above.
Improper Markush Grouping Rejection
11. Claims 1, 44-48, 50-55 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 claims recite the following Markush groups:
- at least one nucleic acid biomarker from blood, plasma or serum comprising ofmiR-100, miR-138, miR-486, miR-9, miR-32, miR-146b, miR-92a, miR-576, miR-142-3p, miR-505, miR-29b, miR-32, miR-505, miR-502-3p, miR-103, miR-98, miR-141, miR-34a, miR-140-3p, miR-329, miR-454, miR-95, and/or miR-886-3 (clm 1);
- at least one protein biomarker from saliva, blood, plasma or serum comprising [[of]] S100A8, F13A1, IGF1, PFN1, FBLN1, CFL1, TMSB4X, TPM4, EFEMPI, KRT16, SPP2, PROC, or PRG4 (clm 1);
-at least one nucleic acid biomarker comprising miR-100, miR-29b, miR-34a, miR- 505 or miR-576 (clm 45);
-at least one protein biomarker comprising S100A8, F13A1, IGF1, PFN1, FBLN1, CFL1, TMSB4X, TPM4, EFEMPi, KRT16, SPP2, PROC, or PRG4 (clm 46);
-at least one of miR-100, miR- 32, miR-505, miR-103, miR-98, miR-242, miR-29b, miR-34a, miR-329, miR-454, miR-95 or miR886-3p (clm 50)
These Markush groupings are 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:
MPEP 2117(II) states that “A Markush claim may be rejected under judicially approved “improper Markush grouping” principles when the claim contains an improper grouping of alternatively useable members. A Markush claim contains an “improper Markush grouping” if either: (1) the members of the Markush group do not share a “single structural similarity” or (2) the members do not share a common use. Supplementary Guidelines at 7166 (citing In re Harnisch, 631 F.2d 716, 721-22, 206 USPQ 300, 305 (CCPA 1980)).
MPEP 2117(II) further state that alternatives (1) share a “single structural similarity” when they belong to the same recognized physical or chemical class or to the same art-recognized class and (2) share a common function or use when they are disclosed in the specification or known in the art to be functionally equivalent in the context of the claimed invention.
MPEP § 2117(II)(A) states that “A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein “there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved”. Herein the members of the Markush grouping are all gene/proteins. These do not belong to the same recognized physical or chemical class or to the same art-recognized class because there is no expectation from the art that each of the recited genes/proteins would function in the same way in the claimed method. It is only in the context of this specification that it was disclosed that all members of this group may behave in the same way in the context of the claimed invention.
MPEP § 2117(II)(B) states that “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 explained in subsection IIA above, the members of the Markush grouping may still be considered to be proper where the alternatives share a substantial structure feature that is essential to a common use. Again the members of the Markush grouping are all gene/proteins. While they are all made up of nucleic acids or amino acids, the structure of comprising nucleic acids or amino acids is not essential to any asserted common use.
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.
Response To Arguments
12. In the response the Applicants traversed the Improper Markush group rejection. Applicants argue that a Markush grouping is improper only if the members do not share a single structural similarity and the members do not share a common use; MPEP 2117. The miRNA groupings and protein groupings of claim 1 share structural similarities either as nucleic acids or as proteins. Furthermore, these miRNAs and proteins share a common use as alternative miRNA or protein biomarkers for detecting FSHD.
This argument has been fully considered but is not persuasive. Members of a Markush group must share a “single structural similarity”.
The examiner acknowledges that the recited miRNAs are all nucleic acid sequences with a sugar phosphate backbone. However the sugar phosphate backbone of a nucleic acid chain is not considered to be a substantial structural feature since it is shared by all nucleic acids and all miRNAs. Further the miRNA do not share any common sequences. Although the sequences, like all miRNA sequences, are made up of the same four bases, they do not share any significant similarity in the order in which those bases are arranged. Thus the structures of the miRNAs represented by the sequences are different.
The examiner acknowledges that the recited proteins are all composed of amino acids. However being composed of amino acids is not considered to be a substantial structural feature since it is shared by all proteins. Further the proteins do not share any common amino acid sequences. Although the sequences, like all proteins, are made up of the same amino acids, they do not share any significant similarity in the order in which those amino acids s are arranged. Thus the structures of the proteins represented by the sequences are different.
Further, the Examiner acknowledges that members of a Markush group share a “single structural similarity” when they belong to the same art recognized physical or chemical class or to the same art recognized class. MPEP 2117 (II)(A) states that
A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved. For example, in the context of a claim covering a disposable diaper, a limitation "the fastener selected from the group consisting of a pressure sensitive adhesive and complementary release material, a complementary hook and loop structure, a snap, and a buckle" would likely be considered an art recognized class because a review of the prior art would establish that it was well known that each member could be substituted for each other with the expectation that the intended result (repositionable and refastenable) would occur.
In the present situation the recited miRNAs/proteins are not members of the same recognized physical or chemical class or the same art-recognized class. Nowhere in the record has it been established or even alleged that the miRNAs/proteins included within the explicit scope of the claims are recognized by the art as being functionally equivalent. There is no expectation from the knowledge in the art that each of the recited miRNAs/proteins will behave in the same way in the context of the claimed invention. The prior art does not teach that the recited miRNAs/proteins could be substituted one for the other, with the expectation that the same intended result would be achieved. There is no evidence of record to establish that it is clear from their very nature or from the prior art that all members possess the common property of being correlated with the radiation exposure. For these reasons the rejection is maintained.
13. 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA HANEY whose telephone number is (571)272-8668. The examiner can normally be reached Monday-Friday, 8:15am-4:45pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached at 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMANDA HANEY/Primary Examiner, Art Unit 1682
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