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 .
Claim Objections
Claims 2 and 3 are objected to because of the following informalities: the claims recite the phrase “administering the subject … a treatment”, where the phrase “administering to the subject … a treatment” is likely intended.
Appropriate correction is required.
The status identifier presented with claim 17 of 12/09/2022 is inappropriate and not consistent with the requirements of 37 CFR 1.121. The claim is identified as “New”, but there is a claim 17 in the originally claim listing. Applicants are encouraged to carefully review any future presented claims to ensure they are compliant with 37 CFR 1.121.
Claim Rejections - 35 USC § 112 – Failure to Limit
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 20 and 24 are each 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 20 recites a limitation related to the location of a mutation in a gene that “encodes a tRNA, a protein and/or a rRNA”, where the limitation appears to encompass all type of genes in the mitochondrial genome (e.g.: all genes in the mitochondrial genome encode a tRNA, a protein and/or a rRNA). Though the claim is rejected under 112(b) as unclear (see rejection later in this Office Action), where the claim may require a gene, the limitation as noted above is not further limiting.
Claim 25 recites a claim directed to the “use” of a sample. The rejected claim adds no practical limitations to the methods of claim 1, where claim 1 requires “assaying a stool sample from the subject”, and is thus already directed to a “use of a stool sample”.
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 - Indefiniteness
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 1-25 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 1, 4, 5, 10-23 and 25 are unclear over recitation of the purpose of the claimed methods as “providing a diagnosis and/or prognosis”, as recited in the preamble of claim 1. Claim 1 does not recite any active step of diagnosing or prognosing. Claim 1 recites “wherein an increase in the level as compared to the reference value is indicative of” elements related to a mitochondrial disorder, but this assertion of a relationship between a compared level and the elements is not itself a step of diagnosing or prognosing; nor is the asserted relationship set forth in the “wherein” clause any requirement that the compared amount (i.e.: an increase in the level as compared to the reference value) is in fact present and detected.
Claims 2 and 23 are unclear over recitation of the purpose of the claimed methods as “providing a diagnosis and/or prognosis”, as recited in the preamble of claim 2, for the same reasons as set forth in regard to claim 1 above.
Claims 2 and 23 are unclear over recitation of the phrase “the subject that has been identified as having or being at risk of having mtDNA disorder”, because there is no antecedent basis for any “subject that has been identified as having or being at risk of having mtDNA disorder”. As noted above, while step b) of claim 2 recites an asserted correlation between a compared level and the presence or risk of a disorder, the wherein clause is not itself a step of identified a subject as having or being at risk of having mtDNA disorder; nor is the asserted relationship set forth in the “wherein” clause any requirement that the compared amount (i.e.: an increase in the level as compared to the reference value) is in fact present and detected.
Claim 3 is unclear over recitation of the phrase “the subject that has been identified as having or being at risk of having mtDNA disorder”, for the same reasons as set forth in regard to claim 2 above.
Claim 5 is unclear over the recitation of the limitation requiring “the subject is a child”, because it is unclear if the limitation intends to require that some particular aged subject is required or encompassed. Neither the claims, the specification, nor the related are provide any limiting, defining age requirements for a subject to be considered a “child”.
Claim 6 is unclear over recitation of the phrase “the sample from the healthy subject”, because there is no antecedent basis for any “healthy subject” or any “sample from the healthy subject” in either claim 6, or in claim 1 from which claim 6 depends.
Claim 7 is unclear over recitation of the limitation “wherein a decrease in the level obtained in step b) as compared to the level in step a) is indicative of the treatment having therapeutic effect”. The methods of claim 7 is directed to “evaluating therapeutic effect of a treatment”, as recited in the preamble. It is unclear if the method is intended to require that the treatment is determined to have a therapeutic effect, or if the claim is intended to encompass making an evaluation that determines that an applied treatment does not have a therapeutic effect. It is unclear if the claim is intended to require that a level in b) is decreased a compared to a level in a), or other compared levels are encompassed by the claim.
Claim 8 is unclear over recitation of the limitation “wherein a decrease in the level obtained in step b) as compared to the level in step a) indicates that the subject is/and or has complied with the prescribed treatment” for the same reasons as set forth in regard to claim 7 above.
Claim 8 is unclear over recitation of the limitation “wherein a change in the levels measured in a) and b) indicates a change in the progression of the mtDNA disorder in the subject” for the same reasons as set forth in regard to claim 7 above.
Claim 14 is unclear recitation of the limitation “wherein sequencing is by pyrosequencing, whole genome sequencing, and/or Sanger sequencing”, because there is no requirement for any sequencing in either claim 14 or in claim 1 from which claim 14 depends. The rejected claim may be made more clear in this regard if amended to depend from claim 13 which requires “sequencing mtDNA molecules or fragments thereof”.
Claims 20 and 22 are unclear recitation of the limitation “the gene encodes a tRNA, a protein and/or a rRNA”, as recited in claim 20, because there is no requirement for any gene in claim 20, or in claims 1 or 18 from which claim 20 depends. The rejected claim may be made more clear in this regard if amended to depend from claim 19 which requires “the mutated mtDNA comprises a mutation in a gene and/or in a non-coding region of the mtDNA”.
Claim 21 is unclear recitation of the limitation “the gene encoding a tRNA is MT-TL1”, because there is no requirement for any gene encoding atRNA in claim 21, or in claims 1 or 19 from which claim 21 depends. The rejected claim may be made more clear in this regard if amended to depend from claim 20 which requires “the gene encodes a tRNA, a protein and/or a rRNA”. Note that claim 20 is itself indefinite as set froth above.
Claim 22 is unclear over the limitation “the mutation is m.3243A>G”. The claim depends from claims 20, 18 and 1, where claim 18 encompasses mitochondrial disorders that are not consistent with the requirement for a mutation that is m.3243A>G (as recited in claim 22) and the mutation being indicative of the disorder (as recited in claim 1). For example, it is unclear how the requirement for m.3243A>G is consonant with the particular encompassed disorder Kearns-Sayre syndrome (KSS), where KSS is primarily caused by a large, spontaneous deletion in the mitochondrial DNA, not the particular point mutation m.3243A>G.
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 1-25 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a abstract ideas and natural phenomena without significantly more.
The claim(s) recite(s) steps related to the comparing of data (e.g.: step b) in claims 1 and 2; relevant to step a) in claim 3; step c) in claims 7,8 and 9). The comparison of data is a mental process which is an abstract idea (see MPEP 2106.04(a)(2)(III)). Additionally, claim 3 recites a step of “requesting”, which is providing an instruction, and is also an abstract idea (see MPEP 2106.04(a)(2)(II)). The claims are further directed to an association between the presence of a mitochondrial mutation and the risk or presence of a mitochondrial disorder. This association is a part of naturally occurring biological processes, and thus in this regard the claims are directed to a natural phenomenon (see MPEP 2106.04(b)).
This judicial exception is not integrated into a practical application because the claims do not require any particular tangible or practical steps that are specifically related to the judicial exception(s) as identified above. For example, the methods of claim 1, 7, 8 and 9 end with an abstract idea (a step of comparing). Here it is noted that while some of the claims set forth a step of administering a treatment, the claims include on a generic treatment which is not sufficient to integrate the judicial exception into a practical application. See MPEP 2106.04(d)(2). The broadly recite step of administering a treatment for a diagnosed condition, as encompassed by the claims, is essentially an instruction to recognize the association set forth in the claims and “apply it”. See MPEP 2106.05(f). In this regard it is noted that while claim 23 recites treatments with some level of particularity, the recitation is not sufficient to integrate the diagnosing/prognosing of claim 2 (from which claims 23 depends) into a practical application because claim 23 recites only general compounds or activities, without any indication of what is actually required to provide any ameliorative effects. For example: what amount of resistance training is an effective treatment for CPEO; what treatment regimen of creatine will alleviate MILS.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements are the necessary data gathering steps required to observe the judicial exception(s) of the claims. Recited at a high level of generality, these steps of the claims are insignificant extra-solution activity (see MPEP 2106.05(g)), and do not produce a method that is significantly more than the identified judicial exception(s). In this regard it is noted that while the claims are directed to the analysis of mitochondrial DNA sequence elements in stool samples, such methods are considered well understood, routine and conventional in the related art, as evidenced by Birch-Machin et al (2005) (cited on the IDS of 07/12/2023), Hopwood et al (1996) (cited on the IDS of 12/05/2023), Srivathsan et al (2016), and Perry et al (2010).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 4, 5, 10-13, 15-17, 24 and 25 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Birch-Machin et al (2005) (cited on the IDS of 07/12/2023).
Birch-Machin et al teaches methods related to the analysis of sequence alterations in mitochondrial DNA (mtDNA) sequences for the detection of pathology related to the alteration. Relevant to claims 1 and 24, Birch-Machin et al teaches that a variety of sample types are suitable for obtaining mtDNA for sequence analysis, including fecal matter (e.g.: para 0141), relevant to the instantly claimed methods which require assaying a stool sample. Further relevant to the method of claim 1, the reference teaches detecting the presence of mutations in mtDNA from a sample (e.g.: para 0126), and teaches detections relevant to measurement of a “level”, as recited in the claims (e.g.: para 0021, para 0092; Table 2; para 0226).
The reference further teaches comparing a mutation in a sample to a database related to a non-disease phenotype, where the presence of the mutation is indicative of the disease state (e.g.: para 0038; para 0052, para 0061; para 0122-0126).
Relevant to the limitations of claims 4 and 5, the reference teaches that a database for comparison can comprise sequence information from healthy controls that do not have the pathology (e.g.: para 0049; para 0056; para 0063; para 0065).
Relevant to the limitations of claims 10-13, the reference teaches that mtDNA may be extracted form a sample (e.g.: para 0048-0060), relevant to claim 10, and teaches that the assaying to detect mutations may include PCR amplification (relevant to claims 11 and 2) and sequencing (relevant to claim 13) (e.g.: para 0147-0154).
Relevant to claim 15, the reference teaches determining a proportion of mutant positions in a sample (e.g.: para 0157).
Relevant to claims 16, 17 and 25, the reference teaches that mtDNA analysis methods are applicable to human subjects (e.g.: para 0013-0021).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 2, 6, 7, 8, 9, 14, 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Birch-Machin et al (2005) (cited on the IDS of 07/12/2023).
The teachings of Birch-Machin et al (2005), as relevant to the steps of the instantly rejected claims which require detection of a mutation level in mtDNA from a stool sample from a subject, and comparison of levels to a reference value, have been addressed previously in this Office Action.
Relevant to the instant rejection of claim 2, the reference suggests that the analysis of mutations in mtDNA can be used as a confirmatory diagnostic which allows for early preventative treatment (e.g.: para 0244).
Relevant to the instant rejection of claims 7 and 8, the reference suggests that the analysis of mutation in mtDNA can be used to monitor a patient’s response to therapeutic treatments (e.g. paras 0177, 0204).
Relevant to the instant rejection of claim 9, the reference teaches that changes or mutations in the mitochondrial genome can be used as markers for disease progression when monitored at successive intervals (e.g.: paras 0006, 0044), and suggests repeating steps of the analysis at different times to monitor progression (e.g.: para 0064).
Relevant to the rejection of claim 14, the reference teaches that the entire mtDNA genome may be considered in the detection of relevant mtDNA mutations (e.g.: paras 0012, 0015, 0023), which is relevant to the “whole genome sequencing” limitation of claim 14.
Relevant to the rejection of claim 19, the reference teaches an analysis of mutation detection in the non-coding region of mtDNA (e.g.: 0212).
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to performed the methods suggested by Birch-Machin et al (e.g.:, provide a treatment to a patient; monitor a patient’s response to therapeutic treatments) using the methods of mtDNA mutation detection in a fecal sample as taught by Birch-Machin et al. The skilled artisan would be motivated to provide treatments and apply the methods to subjects treated with therapeutics based on the expressed teachings of Birch-Machin et al that detection of mtDNA mutations are relevant to such aspects of diseases related to mtNDA mutations. With regard to claims 7, 8, and 9 where Birch-Machin et al teaches that mutations in mtDNA are related to the presence of pathology, the skilled artisan would recognize that a decrease in the amount of mutant mtDNA would indicate that an applied therapy is efficacious in the treatment of the pathology (relevant to claim 7); with regard to claim 8 where any subject is treated with a therapeutic that is known to be efficacious in the treatment of the pathology the skilled artisan would recognize that the amount of mutant mtDNA that is related to the pathology would provide a measurable parameter associated with the patient’s use, or non-use, of the therapeutic; with regard to claim 9 the skilled artisan would recognize that an increased in an amount of mutations associated with pathology would indicated advancement of progression of the pathology (e.g.: para 0044).
Relevant to the rejection of claim 6, the reference teaches that samples such as urine, stool and blood (paras 0042, 0067, 0179) can be used to detect mutation in mtDNA, and teaches the use of samples to create sequence databases (para 0141) as well as databases related to mtDNA sequence in non-disease states (e.g.: paras 0048, 0049, 0056, 0060 and 0063). It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have used the same sample types that are used in diagnostic steps (e.g.: urine, stool and blood) to obtain mtDNA sequence in healthy control subjects for a database of mtDNA sequences that are not associated with disease (as taught by the reference). The skilled artisan would have been motivated to use such sample based on the expressed teachings of Birch-Machin et al that a variety of samples, including those encompassed by the rejected claim, are suitable or the purpose of constructing a mtDNA sequence database, and such samples can be collected by any known means (e.g.: para 0141).
Claim(s) 3, 18 and 20-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Birch-Machin et al (2005) (cited on the IDS of 07/12/2023) in view of Zsurka et al (2007).
The teachings of Birch-Machin et al (2005), as relevant to the steps of the instantly rejected claims which require detection of a mutation level in mtDNA from a stool sample from a subject, and comparison of levels to a reference value, have been addressed previously in this Office Action.
Birch-Machin et al does not exemplify the requesting of a test (claim 3) or the particular diseases of claim 18 or particular mutations relevant to claims 20-22. However, such elements related to mtDNA mutations associated with pathology were known in the art and are taught by Zsurka et al.
Zsurka et al teaches (e.g.: p.298- Subjects; Figure 2) analyses of mtDNA including the detection of A3243G/G16428A mutations (relevant to claims 20-22 the m.3243A>G mutation is in the tRNA Leu(UUR) gene (MT-TL1)) in a subject with MELAS (relevant to claim 18). Relevant to the rejection of claim 3, Zsurka et al teaches (p.298 - mtDNA Mutation Analysis) that sequencing of mitochondrial genome-related DNA was performed on an automatic sequence analyzer by a commercial sequencing service (MWG Biotech).
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have incorporated the teachings of Zsurka et al, including the sequencing of mtDNA using an external sequencing service, which is a request for a test as recited in claim 3, and the detection of A3243G mutations associated with MELAS, in the methods for stool sample analysis taught by Birch-Machin et al. The skilled artisan would have been motived to request a test based on the expressed teachings of Zsurka et al that a commercial sequencing service provides results suitable for the detection of mtDNA mutations; and the skilled artisan would have been motived to include the analysis of A3243G mutations associated with MELAS based on the expressed teachings of Zsurka et al that such mutations are a detectable diagnostic element related to the presence of pathology.
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Birch-Machin et al (2005) (cited on the IDS of 07/12/2023) in view of Ames et al (2002).
The teachings of Birch-Machin et al (2005), as relevant to the steps of the instantly rejected claims which require detection of a mutation level in mtDNA from a stool sample from a subject, comparison of levels to a reference value, and treatment of patients, as required by claim2 from which instantly rejected claim 23 depends, have been addressed previously in this Office Action.
Birch-Machin et al does not exemplify a treatment that includes B complex vitamins, as recited in claim 23. However, such treatments for diseases related to mtDNA mutations were known in the prior art and are reviewed by Ames et al.
Ames et al teaches that mitochondrial B complex vitamins such as riboflavin and nicotinamide are therapeutically beneficial in the treatment of patients with a mutation (3243A→G) in the mitochondrial gene for tRNA leucine (UUR) (e.g.: p.631 - Mitochondrial transfer RNA leucine (UUR): complex I deficiency, MELAS syndrome, migraine, and myopathy; p.635 - Mitochondrial transfer RNA leucine (UUR): MELAS syndrome).
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have detected the 3243A→G mutation and provided a B complex treatment to a subject, as taught by Ames et al, using the mutation detection and treatment methods rendered obvious by Birch-Machin et al. the skilled artisan would have been motivated to apply the methods of Birch-Machin et al to the detection of the 3243A→G mutation and treatment with riboflavin and nicotinamide based on the expressed teachings of Ames et al that the mutation is related to MELAS, and that treatment with B complex vitamins results in measurable improvement of pathological indicators.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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, Anne Gussow can be reached at (571)272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Stephen Kapushoc
Primary Examiner
Art Unit 1684
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683