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 . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Election/Restrictions
Applicants elected group I (treatment) using SEQ ID 14 without traverse in the reply filed on 29 Oct, 2024.
Claims Status
Claims 1, 2, and 38 are pending.
Claims 1, 2, and 38 have been amended.
Withdrawn Rejections
The rejection of claims 1, 2, 38, 54, and 55 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph due to lack of written description is hereby withdrawn due to amendment.
The rejection of claim 54 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph due to the addition of new matter is hereby withdrawn due to amendment.
Maintained/Modified Rejections
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1, 2, 26, 38, 54, and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Cherqui (WO 2017165167, cited by applicants) in view of Lake et al (Ann. Neurol. (2016) 79 p190-203), Payne (US 8,283,444), Massodi et al (Molecules 92009) 14 p1999-2015), and Sutton et al (Cancers (April, 2019) 11, 557)
Cherqui discusses treatment of disorders associated with mitochondrial dysfunction by administering a hematopoietic stem cell transfected with human frataxin (abstract). Such cells are presumed to be generating the protein, and so administering them comprises administering the protein. The mitochondrial disease can be Leigh syndrome, and administration of the stem cells corrects neurologic, cardiac, and muscular complications within about 6-12 months of transplantation (paragraph 13).
The difference between this reference and the examined claims is that this reference discusses treating a genus of diseases that include applicant’s claimed disorder, and does not discuss TAT fusion proteins.
Lake et al discusses Leigh syndrome (title). This is the most common pediatric presentation of mitochondrial disease, and is genetically heterogenous, with mutations in either mitochondrial or nuclear genomes (abstract). Leigh syndrome, French Canadian type is one of these, due to a mutation in LRPPRC (p194, 2nd column, 2nd paragraph). This reference states that the disorder treated by the claimed method is a subset of the disorder treated by Cherqui.
Payne et al discusses methods to deliver compounds to mitochondria (title) to treat mitochondrial disorders, such as many of the disorders discussed by Cherqui (column 1, line 20-26). This is done by attaching TAT to the sequences (column 8, line 14-21), with the sequence YGKKRRQRRR given as an example (table 1, columns 7 and 8, bottom of page). Frataxin is explicitly mentioned as a polypeptide that can be used in the invention (column 9, line 20), and an example of this conjugate are made (column 26, line41-53) and tested in an animal model of Freidreich’s ataxia (column 27, line 9-28), one of the disorders mentioned by Cherqui. This reference shows that the disorders of Cherqui can be treated with a TAT-frataxin conjugate.
Massodi et al discuss TAT attached to an elastin like peptide-lactoferin conjugate (abstract). The TAT sequence is MYGRKKRRQRRR (p209, 2nd paragraph), identical with that used by applicants and very similar to that used by Payne.
Sutton et al discusses a sequence comprising TAT attached to the switch II region of DIRAS3 (abstract). A diglycine linker was included between the TAT sequence and the active peptide to prevent interaction between the two motif and to add flexibility to the peptide (5th page, 1st paragraph). This reference discusses diGly linkers in the context of TAT.
Therefore, it would be obvious to use the sequence of Cherqui for the French Canadian variant of Lake et al, as Lake et al teaches this variant is included in the genus of disorders treated by the invention of Cherqui. As this is inclusive, an artisan in this field would attempt this therapy with a reasonable expectation of success.
Furthermore, it would be obvious to use the TAT-frataxin conjugate of Payne to treat the disorders of Cherqui, as Payne states that these can be used to treat mitochondrial disorders, and provide an example with an animal model of one of the disorders of Cherqui. As this is very similar to the therapy of Cherqui, an artisan in this field would attempt this therapy with a reasonable expectation of success.
In addition, it would be obvious to use the TAT sequence of Massodi et al instead of the TAT sequence of Payne, as a simple substitution of one known element for another yielding expected results. As the sequence of Massodi et al comprises the sequence of Payne, an artisan in this field would make this substitution with a reasonable expectation of success.
Finally, it would be obvious to include a Gly-Gly linker between the TAT and the frataxin, as Sutton et al teaches that this will prevent interaction between the two sequences and add flexibility to the peptide. As Sutton et al used this linker in the context of TAT, an artisan in this field would attempt this modification with a reasonable expectation of success.
Cherqui, Lake et al, and Payne render obvious treating Leigh syndrome, French Canadian type with a TAT-frataxin conjugate. Massodi et al renders obvious using the sequence MYGRKKRRQRRR for TAT, and Sutton et al renders obvious adding a diglycine linker between the TAT and the frataxin. Note that this is SEQ ID 14, rendering obvious claims 1, 2, 26, 38, 54, and 55.
response to applicant’s arguments
Applicant argues that there is no reasonable expectation of success.
Applicant's arguments filed 11 Sept, 2026 have been fully considered but they are not persuasive.
Applicant first describes the work they have done in this project, and some of the discoveries made. It is agreed that applicant has worked hard and has made some important discoveries. Unfortunately, that is not sufficient to make an application based on that work patentable under US patent law.
Applicant argues that Cherqui does not give enough information to give a reasonable expectation of success. However, as has been noted before, a reference is presumed to be enabled (MPEP 2121(I)). This means that the statement in that reference that frataxin can treat Leigh Syndrome is sufficient to provide a reasonable expectation that treating a patient with Leigh Syndrome with frataxin will provide a benefit. Legally, there is no requirement that the reference describe the mechanism of action, provide examples, or anything else that applicant suggests is required.
Conclusion
THIS ACTION IS MADE FINAL. 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 FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
