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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 56-69, in the reply filed on 4/20/2026 is acknowledged.
Claims 70-75 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/20/2026.
In response species election, applicant elected (i) a peptide inhibitor of the full-length MAML2. HTRA2, BIRC2, TRAF-2, MTFRI, ARNT in claim 60 and a cancerous cell of claim 68. Thus, the other peptide sequences of SEQ ID NOs: 1-2, 5-9, and 11-14 in claim 61 as well as claims and 64-65 and 67 are further withdrawn as directed to non-elected species. A rejoinder may be possible after a patentable subject matter has been identified.
Claim Status
Claims 56-75 are pending.
Claims 1-55 are cancelled.
Claims 61, 64-65, 67, and 70-75 are withdrawn as being directed to a non-elected invention, the election having been made on 4/20/2026.
Claims 56-60, 62-63, 66, and 68-69 have been examined.
Priority
This application is a 371 of PCT/IL2022/050230 03/02/2022
PCT/IL2022/050230 has PRO 63/155,819 03/03/2021
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/4/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Objections
Claim 60 is objected to because of the following informalities:
Claim 60 contains the acronyms “MAML2”, “HTRA2”, “BIRC2”, “TRAF-2”, “MTFRl”, and “ARNT”, and an acronym in the first instance of claims should be expanded upon/spelled out as “Mastermind-like protein 2”, “Serine peptidase 2”, “Baculoviral IAP2 repeat”, “TNF receptor associated factor 2”, “mitochondrial fission regulator 1”, and “aryl hydrocarbon receptor nuclear translocator isoform 1” with the acronym indicated in parentheses as (MAML2), (HTRA2), (BIRC2), (TRAF-2), (MTFRl), and (ARNT) respectively after the full names of proteins. The abbreviations can be used thereafter.
Appropriate correction is required.
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 56-60, 62-63, 66, and 68-69 are rejected under 35 U.S.C. 101 because the claimed agent encompasses a naturally-occurring mitochondrial serine protease HtrA2/Omi. The eligibility of patent subject is further analyzed as follows.
Step 1. The claim is directed to a product of natural protein.
Step 2A-Prone 1 (if judicial exception is cited). No. claim 56 is directed to an agent of a naturally-occurring protein capable of modulating the activity of a phosphatidylserine decarboxylase (PSD) within a mammalian cell, encompassing a naturally-occurring mitochondrial serine protease HtrA2/Omi comprising L-amino acids.
Step 2A prong 2 (whether the claim as whole integrates the recited judicial exception into a practical application of the exception): No, there is nothing in the claim to integrate the judicial exception (JE) into any particular practical application. The amounts in the claims are the amounts in which the peptides naturally occur.
Step 2B inventive concept (evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim): No, there is nothing in the claim that causes it to amount to significantly more than the JE. Again, the claim is drawn to a naturally-occurring protein capable of modulating the activity of a phosphatidylserine decarboxylase (PSD) within a mammalian cell such as cancer cells. Because claims 56-60 fail to satisfy eligibility of patent subject, claims 19-20 are rejected under 35 U.S.C. 101 as a natural flax seed oil extract.
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With respect to claims 62-63, the addition limitation of a mitochondria targeting domain at N-terminus is an inherent structure of serine protease HtrA2/Omi evidenced by Walle et al. (Cell Death and Differentiation (2008) 15, 453–460, cited in IDS) shown above (p454, Fig 1).
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With respect to claim 66, the addition limitation of a cell penetrating moiety encompasses a naturally-occurring cell-penetrating peptide as evidenced by Henriques et al. (Biochem. J. (2006) 399, 1–7. See p1, last para, last line). Furthermore, the use of a cell-penetrating peptide to translocate biological membrane to overcome the impermeable nature of the cell membrane is a routine and conventional biotechnique as evidenced by Henriques et al. (Abstract; p2, Table 1; p5, Fig 1).
With respect to claim 68, the addition limitation of a cancerous cell encompasses a naturally-occurring cancer cell.
With respect to claim 69, the addition limitation of one pharmaceutically acceptable diluent, excipient or carrier encompasses a naturally-occurring product, such as water, albumin (a stabilizer for protein formulation), or polysaccharide.
Claims 56-60, 62-63, 66, and 68-69 either encompass a naturally-occurring mitochondrial serine protease HtrA2/Omi or a combine of the protein with other naturally-occurring products as described above; thus, the claims fail to satisfy the eligibility of patent subject.
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.
Claims 56-58 and 68-69 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bellance et al. (Int. J. Mol. Sci. 2020, 21, 1317, previously cited 2/18/2026).
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Claim 56 is drawn to an agent capable of modulating the activity of a phosphatidylserine decarboxylase (PSD) within a mammalian cell.
Bellance et al. teach “Doxorubicin Inhibits Phosphatidylserine Decarboxylase and Modifies Mitochondrial Membrane Composition in HeLa Cells” (Title) as shown follows (p4, Fig 2), reading on claims 56-58 and 68.
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With respect to claim 69, Bellance et al. teach a pharmaceutical composition comprising Doxorubicin (DXR) in a pharmaceutically acceptable diluent to treat Hela cells as shown follows (p3, Fig 1B).
Claims 56-58 and 68-69 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bellance et al. (Int. J. Mol. Sci. 2020, 21, 1317, previously cited 2/18/2026).
Claim 56 is drawn to an agent capable of modulating the activity of a phosphatidylserine decarboxylase (PSD) within a mammalian cell.
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.
1. Claims 56-59, 62, 66, and 69 are rejected under 35 U.S.C. 103 as being unpatentable over Igarashiet al. (J Biol Chem. 1995 Dec 8;270(49):29075-8) in view of Slastnikova et al. (Front. Pharmacol. 2018; 9:1208).
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Claim 56 is drawn to an agent capable of modulating the activity of a phosphatidylserine decarboxylase (PSD) within a mammalian cell.
Igarashiet al. teach a monoclonal anti-idiotypic antibody, Id8F7, able to bind phosphatidylserine decarboxylase (PSD) in the Abstract as shown follows (p29077, col 1, figure 3).
Igarashiet al. did not specify delivery of the antibody into a cell.
Slastnikova et al. teach “Targeted Intracellular Delivery of Antibodies”(Title). Slastnikova et al. teach an antibody can be delivered into cells by conjugation with a protein transduction domain (reading on cell-penetrating moiety) and an antibody can be further modified with a targeting moiety of a nuclear localization sequence or mitochondrial localization sequence for intracellular delivery of the antibody as shown follows (p6, Fig 2).
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Because Slastnikova et al. teach methods of delivering antibody into a cells and the antibody can be further linked to a nuclear localization sequence or mitochondrial localization sequence for intracellular delivery of the antibody known in the art, one of ordinary skill in the art would have found it obvious to combine Igarashiet’s anti-phosphatidylserine decarboxylase antibody with Slastnikova’s teachings of Targeted Intracellular Delivery of Antibodies (Title; p6, Fig 2) to modulate phosphatidylserine decarboxylase in cells, reading on claims 56-59.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine Igarashiet al.in view of Slastnikova et al. because (a) Igarashiet et al. teach the use of anti-phosphatidylserine decarboxylase antibody to modulate phosphatidylserine decarboxylase activity in vitro and (b) Slastnikova et al. teach an antibody can be delivered into cells by conjugation with a protein transduction domain (reading on cell-penetrating moiety) and an antibody can be further modified with a targeting moiety of a nuclear localization sequence or mitochondrial localization sequence for intracellular delivery of the antibody (p6, Fig 2). The combination would have reasonable expectation of success because both references teach the use of an antibody bound to a target.
With respect to claim 62, Slastnikova et al. show an antibody can be beneficially linked to a nuclear localization sequence or mitochondrial localization sequence for intracellular delivery of the antibody (Title; p6, Fig 2).
With respect to claim 66, Slastnikova et al. show an antibody fusion to a protein transducing domain for enhancing the permeability of the peptide through the plasma membrane of a cell (p6, Fig 2).
With respect to claim 69, Slastnikova et al. show a pharmaceutical composition comprising an antibody (e.g., an anti-phosphatidylserine decarboxylase antibody) and a pharmaceutically acceptable carrier of nanoparticle (p6, Fig 2).
2. Claims 56-59, 62, 66, and 68-69 are rejected under 35 U.S.C. 103 as being unpatentable over Igarashiet al. in view of Slastnikova et al. as applied to claims 56-59, 62, 66, 69 and further in view of Bellance et al.
Claim 68 is drawn to the cell is a cancerous cell.
Igarashiet al. in view of Slastnikova et al. teach delivery of an anti-phosphatidylserine decarboxylase antibody into a cell.
Igarashiet al. in view of Slastnikova et al. did not specify delivery of an anti-phosphatidylserine decarboxylase antibody to treat cancerous cells.
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Bellance et al. show inhibition of phosphatidylserine decarboxylase to treat cancer cells at a dose-dependent manner (p3, Fig 1B). Because Bellance et al. show inhibition of phosphatidylserine decarboxylase able to treat cancerous cells, one of ordinary skill in the art would have found it obvious to administer Igarashiet’s anti-phosphatidylserine decarboxylase antibody to kill cancerous cells.
One ordinary skill in the art would have found it obvious to combine (i) Igarashiet al. in view of Slastnikova et al. and (ii) Bellance et al. because (a) Igarashiet al. in view of Slastnikova et al. teach delivery of an anti-phosphatidylserine decarboxylase antibody into cells and (b) Bellance et al. show inhibition of phosphatidylserine decarboxylase able to kill cancerous cells (p3, Fig 1B). The combination would have reasonable expectation of success because the references teach administration of a phosphatidylserine decarboxylase inhibitor into cells.
Conclusion
No claim is allowed.
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/J.L/Examiner, Art Unit 1658
27-June-2026
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
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