DETAILED ACTION
America Invents Act
The present application is being examined under the pre-AIA first to invent provisions. 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 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
Applicant elected group II, treating PAH with SEQ ID 1 and an MFN2 AAV gene therapy vector with traverse in the reply filed on 22 Sept, 2021. The traversal was found unpersuasive, and the election/restriction requirement made final in the office action of 10 Nov, 2022. In the response of 11 April, 2022, applicant amended the claims so they no longer read on applicant’s elected species. In the response of 12 March, 2023, applicants amended the claims so their elected species again reads on the claims.
Claims Status
Claims 5, 14, and 15 are pending.
Claim 5 has been amended.
Withdrawn Rejections
The rejection of claims 5, 14, and 15 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite due to non-therapeutic agents listed as therapies is hereby withdrawn due to amendment.
The rejection of claims 5, 14, and 15 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Komatsu et al (WO 2011106788) in view of Marsboom et al (Circ. Res. (2012) 110 p1484-1497), Zorzano et al (Life (2006) 58(7) p441-443), Chen et al (J. Cell Biol. (2006) 160 (2) p189-200), and Robbins et al (Pharmacol. Ther. (1998) 80(1) p35-47) is hereby withdrawn due to amendment.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
Claims 5, 14, and 15 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Komatsu et al (WO 2011106788, cited by applicants) in view of Marsboom et al (Circ. Res. (2012) 110 p1484-1497, available 24 May, 2012, previously cited), Zorzano et al (Life (2006) 58(7) p441-443, previously cited), Chen et al (J. Cell Biol. (2006) 160 (2) p189-200, previously cited), Robbins et al (Pharmacol. Ther. (1998) 80(1) p35-47, previously cited), and Stringham et al (Am. Fam. Physician (2010) 82(4) p370-377)
Komatsu et al discuss the CAR peptide for therapy of pulmonary disorders (title). This can include administering a peptide of SEQ ID 1 or SEQ ID 2 (identical to SEQ ID 1 and SEQ ID 2 of the instant application) and a bioactive agent to an animal in need thereof (p 12, 3d paragraph, continues to p13). Pulmonary hypertension is listed as a specific disorder to be treated (p18, 4th paragraph, continues to p19). While this reference does not discuss what the peptide binds to, this is the same peptide so will necessarily bind to the same species. Bioactive agents comprise small molecules, proteins, peptides, viral vectors, antisense agents, polynucleotides, and other compounds (p14, 1st paragraph). Note that viral vectors are presumed to be a gene transfer therapy. These can be bound to each other or unbound (p12, 2nd paragraph). Therapeutics can be co-administered with the peptides (p12, 3d paragraph). The peptide is assumed to bind to cell surface heparin sulfate and internalizes (p5, 2nd paragraph).
The difference between this reference and applicant’s elected species is that this reference does not teach an adeno-associated virus inserting a gene for MFN2 or a second therapeutic.
Marsboom et al discuss DRP1 as a therapeutic target in pulmonary hypertension (title). This disorder is characterized by pulmonary vascular obstruction caused, in part, by pulmonary artery smooth muscle cell hyperproliferation (abstract). MFN2 is described as a polypeptide with the exact opposite action as DRP1 (p1485, 1st column, 2nd paragraph). Note that this polypeptide has decreased expression in pulmonary hypertension patients (p1486, 2nd column, 5th paragraph). Inhibition of DRP1 attenuated pulmonary hypertension in a rat model (p1491, 2nd column, 1st paragraph, continues to p1492). The reference concludes that mitochondrial dynamics are a therapeutic option for this disorder (p1495, 1st column, 2nd paragraph, continues to 2nd column). This reference suggests that MFN2 can be used to treat pulmonary hypertension.
This is confirmed by Zorzano et al. This reference describes the biology of MFN1 and MFN2 (title), and teaches that MFN2 regulates mitochondrial dynamics and is an antiproliferative protein (p442, 1st column, 1st paragraph).
Chen et al discuss MFN1 and MFN2 in the context of embryonic development (title). This involved transfection with a retrovirus with RNA for MFN2 (p199, 1st column, 7th and 8th paragraphs). This reference mentions transfection with MFN2 using a viral vector.
Robbins et al discuss viral vectors for gene therapy (title). The various types of viral vectors, including retroviruses and AAVs, have advantages and disadvantages (abstract), and so require modification and selection to optimize for specific gene therapy applications (p36, 1st column, 3d paragraph). This reference teaches the various viral vectors, and their strengths and weaknesses, and suggest that part of optimizing a gene therapy program involves selection of a specific viral vector.
Stringham et al discuss diagnosis and treatment of PAH (title). Standard treatment options are anticoagulants, diuretics, oxygen supplementation, and calcium channel blockers (for some patients), which can be administered orally (abstract). This reference discusses the therapies for treatment of PAH>
Therefore, it would be obvious to use MFN2 as a treatment for pulmonary hypertension, as this described as having activity similar to inhibition of DRP1 and as a therapeutic by Marsboom et al and confirmed by Zorzano et al. As there are multiple references discussing the activity of this polypeptide, an artisan in this field would attempt this therapy with a reasonable expectation of success.
Furthermore, it would be obvious to use a viral vector as a gene therapy to administer this polypeptide, as Chen et al mention using a similar system in pursuit of their findings. As Robbins et al discuss many of the advantages and disadvantages of such systems, an artisan in this field would use this methodology with a reasonable expectation of success.
Finally, it would be obvious to add this vector to the therapy of Stringham et al, as both therapies are used to treat the same disorder. As the therapies of Stringham et al are the standard treatment for this disorder, an artisan in this field would attempt their use with a reasonable expectation of benefiting the patient.
Robbins et al makes clear that the choice of vector is a matter of optimization. The MPEP states that “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or working ranges by routine experimentation" In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) (MPEP2144.05.II).
Komatsu et al discusses using peptides of SEQ ID 1 to increase efficacy of therapeutics, including gene vectors, to treat disorders, including pulmonary hypertension. Marsboom et al and Zorzano et al render obvious using MFN2 to treat pulmonary hypertension, and Chen et al and Robbins et al render obvious using an adenovirus delivery vector. Robbins et al discuss optimizing uptake, which will reasonably maximize expression of the protein, which will meet the enhancement levels claimed. Stringham et al render obvious adding orally administered diuretics (antihypertensive). While the references are silent about IndoA2S-GlcNS and the mechanism of internalization, the CAR peptide of Komatsu et al is identical to the CAR peptide of applicants, so will necessarily work by the same mechanism. Thus, the combination of references renders obvious claims 5, 14, and 15.
response to applicant’s arguments
Applicant argues that the rejection does not meet the newly added limitation of oral administration.
Applicant's arguments filed 4 July, 2026 have been fully considered but they are not persuasive.
The rejection has been amended to account for this limitation.
New Rejections
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 5, 14, and 15 are 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.
Claim 5, and claims dependent on it, have the newly added limitation that the method of administration is oral. The disclosure has support for the peptide being orally administered (p4, 3d paragraph and p5, 1st paragraph), but not any other component of the formulation. Thus, this amendment constitutes new matter.
Claim Rejections - 35 USC § 112(b)
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 5, 14, and 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5 has been amended to require that “the administration” is oral. However, there are three compounds being administered, the peptide, the adenovirus, and the additional therapeutic; it is not clear which one is “the” administration that must be administered orally.
Conclusion
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 FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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