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 .
Claims 1-20 are pending.
Applicant’s election without traverse of Group I in the reply filed on June 19, 2026 is acknowledged.
Claims 8-20 are withdrawn from further consideration by the examiner, 37 C.F.R. 1.142(b) as being drawn to non-elected inventions.
Claims 1-7, drawn to a cargo molecule transduction domain that has cell-penetrating ability and binds to cargo molecules and transports the cargo molecules into mammalian cells or tissues, the cargo molecule transduction domain comprising:
1) a RMMR1 peptide consisting of SEQ ID NO: 1 derived from human MRPL15; or
2) a RMMR1 variant peptide consisting of 5 to 50 amino acids in which one or more amino acids are deleted, substituted, and/or added to the RMMR1 peptide, are being acted upon in this Office Action.
Priority
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 14, 2023 has been considered by the examiner and an initialed copy of the IDS is included with this Office Action.
Drawings
The drawings are objected to for the following minor informality:
Figures 2A and 2B: The legend of Y-axis is missing.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specification
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
“MRPL152” at p. 2 should have been “MRPL15”.
The “SEQ NO.1” at p. 5 and 21 should have been “SEQ ID NO: 1”.
Nucleotide sequences appearing in p. 21, line 8 which are not identified by sequence identifiers (SEQ ID NO:) in accordance with 37 CFR 1.821(d).
Nucleotide sequences SEQ ID NO: 24 to SEQ ID NO: 46 appearing in Table 2 do not match with the sequences of SEQ ID NO: 24 to SEQ ID NO: 46 in the computer readable form (CRF) for the sequence listing.
Required response – Applicant must provide:
A replacement "Sequence Listing XML" part of the disclosure, as described above submitted in accordance with either item 1. or 2.; together with
A statement that identifies the location of all additions, deletions, or replacements of sequence information in the replacement "Sequence Listing XML" as required by 1.835(b)(3);
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
A statement that the replacement "Sequence Listing XML" includes no new matter as required by 37 CFR 1.835(b)(5); and
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation-by-reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Where to obtain assistance:
USPTO Sequence listing Resource Center at: https://www.uspto.gov/patents/apply/sequence-listing-resource-center.
For rules interpretation and filing requirements, call the Sequence Systems Service Center at (571) 272-2510, the Office of Patent Legal Administration at (571) 272-7701, or, for 35 U.S.C. 371 applications, the PCT Help Desk at (571) 272-4300.
For WIPO Standard ST.26 questions, call (571) 272-2510.
WIPO Sequence software is available at: https://www.wipo.int/standards/en/sequence/index.html.
For assistance with submission of a Sequence Listing XML file via Patent Center, call the Electronic Business Center at (866) 217-9197 or email ebc@uspto.gov.
Claim Objection
Claim 1 is objected to because of the following informalities:
the claim uses the abbreviation “RMMR1” and “MRPL15” without first defining it. To clarify the claim, applicant should first spell out the full term before using an abbreviation. Given the subject matter of the specification, the examiner presumes that "MRPL15" stands for "Mitochondrial Ribosomal Protein Large subunit 15". Appropriate correction is required.
“wherein” is missing at line 2 after “tissue”.
Claim 2 is objected to because of the following informality: “wherein an amino acid substitution” should have been “wherein the amino acid substitution” when referring back to the preceding claim.
Claim 4 is objected to for the following minor informality: “wherein, in a peptide … deleted” should have been “…wherein the RMMR1 variant peptide is a sequence in which one to eight amino acid residues of SEQ ID NO: 1 are deleted”.
Claim 5 is objected to for the following minor informality: “wherein a peptide variant sequence…middle” should have been ““…wherein the RMMR1 variant peptide is a sequence in which at least one amino acid is deleted or added to SEQ ID NO: 1 at an N-terminus, a C-terminus or middle”.
Claim 7 is objected to for the following minor informality: “The cargo molecule …through a linker” should have been “The cargo molecule domain of claim 1, wherein the cargo molecule transduction domain is in the form of a dimer or a multimer”.
Claim Rejections - 35 U.S.C. § 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 1-7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claim 1 recites a cargo molecule transduction domain that has cell-penetrating ability and binds to cargo molecules and transports the cargo molecules into mammalian cells or tissues, the cargo molecule transduction domain comprising:
1) a RMMR1 peptide consisting of SEQ ID NO: 1 derived from human MRPL15; or
2) a RMMR1 variant peptide consisting of 5 to 50 amino acids in which any one or more amino acids are deleted, substituted, and/or added to the RMMR1 peptide.
Claim 2 recites the cargo molecule transduction domain of claim 1, wherein an amino acid substitution in the RMMR1 variant peptide is a conservative amino acid substitution.
Claim 3 recites the cargo molecule transduction domain according to claim 1, wherein the RMMR1 variant peptide is a sequence in which a lysine residue position of SEQ ID NO: 1 is independently substituted with an arginine residue and/or an arginine residue position of SEQ ID NO: 1 is independently substituted with a lysine residue.
Claim 4 recites the cargo molecule transduction domain of claim 1, wherein, in a peptide sequence in which any one or more amino acids are deleted from the RMMR1 variant peptide, any one to eight among the amino acids of the RMMR1 peptide are deleted.
Claim 5 recites the cargo molecule transduction domain of claim 1, wherein a peptide variant sequence in which one or more amino acids are deleted and/or added to the RMMR1 peptide has amino acid deletions and/or additions in any one or more of an N-terminus, a C-terminus, and middle.
Claim 6 recites the cargo molecule transduction domain of claim 1, wherein the mammalian cell is an antigen presenting cell.
Claim 7 recites the cargo molecule transduction domain according to claim 1, wherein one or more of
1) a RMMR1 peptide consisting of SEQ ID NO: 1 derived from human MRPL15; or
2) a RMMR1 variant peptide consisting of 5 to 50 amino acids in which one or more amino acids are deleted, substituted, and/or added to the RMMR1 peptide, is bound in the form of a dimer or higher-order multimer without a linker or through a linker. Thus, the claims are drawn to amino acid sequences which are products of nature.
As evidenced by UniProt Accession number Q9P015, SEQ ID NO: 1 is a fragment of human MRPL15, the highlight region is the claimed SEQ ID NO: 1.
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The specification discloses RMMR1 peptide consisting of instant SEQ ID NO: 1 is a fragment of the naturally occurring protein human MRPL15 (see pages 2-3, paragraph [8] of instant specification). Therefore, human MRPL15 protein (comprising a RMMR1 peptide consisting of instant SEQ ID NO: 1) meets all the structural limitations of the cargo molecule transduction domain recited in instant claims 1-7.
Regarding variants, the specification teaches the ‘peptide’ sequence in which at least 1 to 8 amino acids may be deleted at either terminus or anywhere in the sequence, see p. 9-11, in particular. The variants may include one or more substitutions, deletions, additions and/or insertions. Such variants may be naturally occurring. Thus, the claimed peptides do not sufficiently distinguish over peptides as they exist naturally because the claims do not particularly point out any non-naturally occurring differences between the claimed products and the naturally occurring products.
When a law of nature or natural phenomenon is claimed as a physical product, the courts have often referred to the exception as a "product of nature". For example, the isolated DNA of Myriad and the primers of Ambry Genetics were described as products of nature by the courts. Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 580, 106 USPQ2d 1972, 1975 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014). As explained in those decisions, products of nature are considered to be an exception because they tie up the use of naturally occurring things, but they have been labeled as both laws of nature and natural phenomena. See MPEP 2106.04(b).
Further, the human intervention required by the claims is limited to isolating the natural CRS products into a composition. However, in Myriad, the Supreme Court made clear that not all changes in characteristics will rise to the level of a marked difference, e.g., the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. See MPEP 2106.04(c). Therefore, here, like Myriad, the composition comprising an isolated natural product is not markedly different from the natural product itself because there is no difference in the CRS in its natural and isolated state. This judicial exception is not integrated into a practical application because there are no additional elements that could integrate the judicial exception. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements.
The claims 1-7 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claimed cargo molecule transduction domain in instant claims 1-7 does not recite features or steps demonstrating a marked difference from what exists in nature; and the claimed cargo molecule transduction domain in instant claims 1-7 does not recite meaningful limitations that add something of significance to the judicial exception. Therefore, the claimed cargo molecule transduction domain in instant claims 1-7 is not significantly different than a judicial exception (natural product).
Claim Rejections - 35 USC § 112
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.
Claim 4 is 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 pre-AIA the applicant regards as the invention.
The recitation of “The cargo molecule transduction domain of claim 1, wherein, in a peptide sequence in which one or more amino acids are deleted from the RMMR1 variant peptide, one to eight among the amino acids of the RMMR1 peptide are deleted” is indefinite because it is not clear what is meant by “in a peptide sequence in which one or more amino acids are deleted from the RMMR1 variant peptide, one to eight among the amino acids of the RMMR1 peptide are deleted”. Therefore, the metes and bounds of instant claim 4 is vague and indefinite.
Claim rejections under - 35 U.S.C. 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1-7 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The Written Description Guidelines for examination of patent applications indicates, “the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical characteristics and/or other chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show applicant was in possession of the claimed genus.” (see MPEP 2163).
Claim 1 encompasses a cargo molecule transduction domain that has cell-penetrating ability and binds to cargo molecules and transports the cargo molecules into mammalian cells or tissues, the cargo molecule transduction domain comprising:
1) a RMMR1 peptide consisting of SEQ ID NO: 1 derived from human MRPL15; or
2) a RMMR1 variant peptide consisting of 5 to 50 amino acids in which any one or more amino acids are deleted, substituted, and/or added to the RMMR1 peptide.
Claim 2 encompasses the cargo molecule transduction domain of claim 1, wherein an amino acid substitution in the RMMR1 variant peptide is a conservative amino acid substitution.
Claim 3 encompasses the cargo molecule transduction domain according to claim 1, wherein the RMMR1 variant peptide is a sequence in which a lysine residue position of SEQ ID NO: 1 is independently substituted with an arginine residue and/or an arginine residue position of SEQ ID NO: 1 is independently substituted with a lysine residue.
Claim 4 encompasses the cargo molecule transduction domain of claim 1, wherein, in a peptide sequence in which any one or more amino acids are deleted from the RMMR1 variant peptide, any one to eight among the amino acids of the RMMR1 peptide are deleted.
Claim 5 encompasses the cargo molecule transduction domain of claim 1, wherein a peptide variant sequence in which one or more amino acids are deleted and/or added to the RMMR1 peptide has amino acid deletions and/or additions in any one or more of an N-terminus, a C-terminus, and middle.
Claim 6 encompasses the cargo molecule transduction domain of claim 1, wherein the mammalian cell is an antigen presenting cell.
Claim 7 encompasses the cargo molecule transduction domain according to claim 1, wherein one or more of
1) a RMMR1 peptide consisting of SEQ ID NO: 1 derived from human MRPL15; or
2) a RMMR1 variant peptide consisting of 5 to 50 amino acids in which one or more amino acids are deleted, substituted, and/or added to the RMMR1 peptide, is bound in the form of a dimer or higher-order multimer without a linker or through a linker.
The specification defines the term "cargo molecule transduction domain" refers to a peptide that forms a covalent bond with cargo molecules such as high-molecular organic compounds, such as oligonucleotides, peptides, proteins, oligosaccharides, or polysaccharides, and allows the cargo molecules to be introduced into cells or tissues without the need for separate receptors, carriers, or energy. As used herein, the term "cargo molecule transduction domain" is used interchangeably with "protein transduction domain" or "cell penetrating domain."
The specification discloses a peptide from human Mitochondrial Ribosomal Protein Large subunit 15 wherein the peptide consisting of the amino acid sequence "ERRPRGRRRGRKC” of SEQ ID NO: 1 (also known as RMMR1), wherein the peptide has cell-penetrating ability and binds to green fluorescent protein and transports said green fluorescent protein into a cell in vitro. The specification further discloses variants of SEQ ID NO: 1 selected from the group consisting of SEQ ID NO: 2 to 23, see Table 1 at p. 23-25. The specification discloses fusion protein comprising enhanced green fluorescent protein (EGFP) fused to RMMR1, see p. 17. The RMMR1 peptide can transport the green fluorescent protein into the cytoplasm of various cell lines, e.g., HaCaT, 3T3, B16F10 cells. The specification also discloses RMMR1-FITC and the cell penetration efficiency of RMMR1 was confirmed using cell lines 3T3 and B16F10 (see results 2, FIG. 2) or RAW264.7 cell.
However, the claims do not recite sufficient structure, e.g., amino acid sequence and thus do not meet the written description requirement. Specifically, there is no disclosure of any RMMR1 peptide consisting of 20 to 50 amino acids in length (claim 1, part 2). Other than the isolated RMMR1 peptide consisting of the amino acid sequence of SEQ ID NO: 1-23, the specification does not describe the structure, e.g., amino acid sequence of any cargo molecule transduction domain comprising any RMMR1 variant peptide consisting of 5 to 50 amino acids in which any one or more amino acids are deleted, substituted, and/or added to the RMMR1 peptide.
Regarding peptide variants in which any one or more amino acids are deleted and/or added or substituted, the specification does not describe where and what amino acid within the full-length sequence of RMMR1 peptide of SEQ ID NO: 1 to be deleted, substituted, added or a combination thereof such that the cargo molecule comprising such variant still transport the cargo into the cell cytoplasm, much less binds to any and all possible cargo molecules (claims 1, 4, 5, 7). The specification does not disclose any dimer or higher-order multimer without linker or through a linker comprising RMMR1 peptide of SEQ ID NO: 1 (claim 7). The specification does not disclose any dimer or higher-order multimer without linker or through a linker comprising any RMMR1 variant consisting of 5 to 50 amino acids in which any one or more amino acids are deleted, substituted and/or added to the RMMR1 peptide that has no resemblance to SEQ ID NO: 1 still maintains functions, e.g., binds any cargo molecules, transports any cargo molecules into mammalian cells or tissues (claim 7). A skilled artisan cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus that exhibit this functional property.
Protein chemistry is probably one of the most unpredictable areas of biotechnology. For example,the replacement of a single lysine at position 118 of the acidic fibroblast growth factor by a glutamic acidled to a substantial loss of heparin binding, receptor binding, and biological activity of the protein (seeBurgess, et al., Journal of Cell Biology 111: 2129-2138, 1990; PTO 892).
In transforming growth factor alpha, replacement of aspartic acid at position 47 with asparagine, did not affect biological activity while the replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen (see Lazar, et al. Molecular and Cellular Biology 8: 1247-1252, 1988; PTO 892).
Drumm et al (Annu. Rev. Pathol. Mech. Dis., 7: 267-282, 2012; PTO 892) teach cystic fibrosis is an autosomal recessive disorder caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, for example, page 268, Section “CYSTIC FIBROSIS”. Drumm et al further teach several mutations can cause cystic fibrosis, including two mutations G551D and G551S; and clinical consequences are quite different for these two changes, as the G551D variant has virtually no detectable activity, and consequently a classic, severe phenotype is associated; G551S, however, has reduced but clearly detectable function and is associated with a much milder presentation of CF, for example page 269, left column, the last paragraph. Drumm et al also teach that in the most common cystic fibrosis mutation ΔF508 (the absence of amino acid 508 of the normally 1,480-amino acid protein) gives rise to the cystic fibrosis phenotype, for example, page 268, right column, the 2nd paragraph. As such, even the substitution or deletion of a single amino acid can have dramatic and unpredictable effects on the function of the protein. Thus the identity of the “RMMR1 variant peptide” is needed.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116.).
Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddles v. Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence. Thus, the specification fails to describe these DNA sequences.
For genus claims, an adequate written description of a claimed genus requires more than a generic statement of an invention's boundaries. A patent must set forth either a representative number of species falling within the scope of the genus or structural features common to the members of the genus. Kubin, Exparte, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007); Ariad Pharms., Inc. v. Eli Lilly& Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010).
Therefore, only an isolated peptide from human Mitochondrial Ribosomal Protein Large subunit 15 (MRPL15) wherein the peptide consisting of the amino acid sequence selected from the group consisting SEQ ID NO: 1 to 23, and wherein the peptide transports a cargo molecule into a mammalian cell, (2) The isolated peptide from human Mitochondrial Ribosomal Protein Large subunit 15 (MRPL15) wherein the peptide consisting of the amino acid sequence of SEQ ID NO: 1, (3) a dimer or a multimer comprising two or more peptides each consisting of the amino acid sequence of SEQ ID NO: 1 with or without a linker, but not the full breadth of the claims meets the written description provision of 35 U.S.C. § 112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115).
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 1, 4-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by UniProt Accession Number Q9P015, published Oct 1, 2000; PTO-892).
Claim 1 recites a cargo molecule transduction domain that has cell-penetrating ability and binds to cargo molecules and transports the cargo molecules into mammalian cells or tissues, the cargo molecule transduction domain comprising:
1) a RMMR1 peptide consisting of SEQ ID NO: 1 derived from human MRPL15; or
2) a RMMR1 variant peptide consisting of 5 to 50 amino acids in which any one or more amino acids are deleted, substituted, and/or added to the RMMR1 peptide.
Claim 4 recites the cargo molecule transduction domain according to claim 1, wherein, in a peptide sequence in which one or more amino acids are deleted from the RMMR1 variant peptide, one to eight among the amino acids of the RMMR1 peptide are deleted.
Claim 5 recites the cargo molecule transduction domain of claim 1, wherein a peptide variant sequence in which one or more amino acids are deleted and/or added to the RMMR1 peptide has amino acid deletions and/or additions in any one or more of an N-terminus, a C-terminus, and middle.
Claim 6 recites the cargo molecule transduction domain of claim 1, wherein the mammalian cell is an antigen presenting cell.
Claim 7 recites the cargo molecule transduction domain according to claim 1, wherein one or more of
1) a RMMR1 peptide consisting of SEQ ID NO: 1 derived from human MRPL15.
The accession number Q9P015 reveals a human RM15 protein of 296 amino acids comprising the claimed RMMR1 peptide consisting of SEQ ID NO: 1, see the highlight region is the claimed SEQ ID NO: 1.
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Although the reference does not specifically teach that the peptide has cell-penetrating ability and binds to cargo molecules and transports the cargo molecules into mammalian cells, a chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure as claimed, the properties applicant discloses and/or claims are necessarily present. "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Thus, the reference teachings anticipate the claimed invention.
Claims 1-3 and 6 are rejected under 35 U.S.C. 102 (a)(1)as being anticipated by Baumhof (US20110053829, published March 3, 2011; PTO 892).
Claim 1 recites a cargo molecule transduction domain that has cell-penetrating ability and binds to cargo molecules and transports the cargo molecules into mammalian cells or tissues, the cargo molecule transduction domain comprising:
1) a RMMR1 peptide consisting of SEQ ID NO: 1 derived from human MRPL15; or
2) a RMMR1 variant peptide consisting of 5 to 50 amino acids in which any one or more amino acids are deleted, substituted, and/or added to the RMMR1 peptide.
Claim 2 recites the cargo molecule transduction domain of claim 1, wherein an amino acid substitution in the RMMR1 variant peptide is a conservative amino acid substitution.
Claim 3 recites the cargo molecule transduction domain according to claim 1, wherein the RMMR1 variant peptide is a sequence in which a lysine residue position of SEQ ID NO: 1 is independently substituted with an arginine residue and/or an arginine residue position of SEQ ID NO: 1 is independently substituted with a lysine residue.
Regarding claim 1 part 2), Baumhof teaches a polymeric carrier molecule (aka cargo molecule) capable of binding to cargo molecule, e.g., nucleic acids or genes into cells for efficient transfection of nucleic acids or genes into cells in vivo and vitro, wherein the polymeric carrier molecule comprising a polycationic peptide comprising the amino acid sequence CRRRRRRRRRRRC of SEQ ID NO: 4, which is a variant of instant RMMR1 peptide consisting of 13 amino acids in length having one or more amino acids substitution, see sequence alignment below.
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Claims 2 and 3 are included as Baumhof teaches the reference sequence above has a lysine (K) for an arginine (R), which is a conservative substitution.
Although the reference does not specifically teach that the peptide has cell-penetrating ability and binds to cargo molecules and transports the cargo molecules into mammalian cells, a chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure as claimed, the properties applicant discloses and/or claims are necessarily present. "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Thus, the reference teachings anticipate the claimed invention.
Claims 1, 5 and 6 are rejected under 35 U.S.C. 102 (a)(1)as being anticipated by Chen et al (US20110033389 published February 10, 2011; PTO 892).
Claim 1 recites a cargo molecule transduction domain that has cell-penetrating ability and binds to cargo molecules and transports the cargo molecules into mammalian cells or tissues, the cargo molecule transduction domain comprising:
1) a RMMR1 peptide consisting of SEQ ID NO: 1 derived from human MRPL15; or
2) a RMMR1 variant peptide consisting of 5 to 50 amino acids in which any one or more amino acids are deleted, substituted, and/or added to the RMMR1 peptide.
Claim 5 recites the cargo molecule transduction domain of claim 1, wherein a peptide variant sequence in which one or more amino acids are deleted and/or added to the RMMR1 peptide has amino acid deletions and/or additions in any one or more of an N-terminus, a C-terminus, and middle.
Regarding claims 1 part 2 and 5, Chen teaches a transduction peptide comprises the amino acid sequence of SEQ ID NO: 541 (RGRRRGRKCGR), which is a variant of the claimed RMMR1 peptide, see sequence alignment below. The reference peptide RGRRRGRKCGR consisting of 11 amino acids, which is within the claimed range of 5 to 50 amino acids, and has two amino acids added at the C-terminus.
OTHER INFORMATION: Human 39S ribosomal protein L15
Query Match 69.9%; Score 51; Length 11;
Best Local Similarity 100.0%;
Matches 9; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 5 RGRRRGRKC 13
|||||||||
Db 1 RGRRRGRKC 9
The reference peptide inherently has the claimed functions, e.g., cell-penetrating ability and binds to cargo molecules and transports the cargo molecules into mammalian cells or tissues and transport any cargo molecules into mammalian cells, e.g., antigen presenting cell.
Although the reference does not specifically teach that the peptide has cell-penetrating ability and binds to cargo molecules and transports the cargo molecules into mammalian cells, a chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure as claimed, the properties applicant discloses and/or claims are necessarily present. "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Thus, the reference teachings anticipate the claimed invention.
Claims 1-3 are rejected under 35 U.S.C. 102 (a)(1)as being anticipated by Piwnica-Worms et al (US20030219378 published November 27, 2003; PTO 892).
Claim 1 recites a cargo molecule transduction domain that has cell-penetrating ability and binds to cargo molecules and transports the cargo molecules into mammalian cells or tissues, the cargo molecule transduction domain comprising: a RMMR1 variant peptide consisting of 5 to 50 amino acids in which any one or more amino acids are deleted, substituted, and/or added to the RMMR1 peptide.
Claim 2 recites the cargo molecule transduction domain of claim 1, wherein an amino acid substitution in the RMMR1 variant peptide is a conservative amino acid substitution.
Claim 3 recites the cargo molecule transduction domain according to claim 1, wherein the RMMR1 variant peptide is a sequence in which a lysine residue position of SEQ ID NO: 1 is independently substituted with an arginine residue and/or an arginine residue position of SEQ ID NO: 1 is independently substituted with a lysine residue.
Regarding claims 1 part 2, Piwnica-Worms teaches a membrane-permeant peptide comprises poly-Arg, e.g., RRRRRRRRR (SEQ ID NO: 37), see para. [0076]. The reference peptide RRRRRRRRR consists of 9 amino acids, which is within the claimed range of 5 to 50 amino acids and in which has one or more substitution. The reference peptide covalently linked (aka binds to) transport cargo, e.g., fluorescein (Examples 7-8), diagnostic or pharmaceutically active substance (para. [0106], [0114]) and delivering the cargo into living cells or tissue, see para. [0118], [0119], [0069].
Regarding claims 2-3, Piwnica-Worms teaches that exemplary substitutions can be conservative amino acid changes resulting in silent changes within the present peptides, etc., can be selected from other members of the class to which the naturally occurring amino acid belongs, e.g., basic (positively charged) amino acids such as arginine, histidine, and lysine, see para. [0086], Example 16.
Although the reference does not specifically teach that the peptide has cell-penetrating ability and binds to cargo molecules and transports the cargo molecules into mammalian cells, a chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure as claimed, the properties applicant discloses and/or claims are necessarily present. "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Thus, the reference teachings anticipate the claimed invention.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-7 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-6 of co-pending application No. 18/288,824.
Instant claims 1, 2 and 6 are drawn to a cargo molecule transduction domain that binds to cargo molecules and transports the cargo molecules into mammalian cells or tissues, the cargo molecule transduction domain comprising: 1) a RMAD1 peptide consisting of SEQ ID NO: 1 derived from human ADARB2; or 2) a RMAD1 variant peptide consisting of 8 to 50 amino acids in which one or more amino acids are deleted, substituted, and/or added to the RMAD1 peptide.
Claim 1 of co-pending application No. 18/288,824 is drawn to a cargo molecule transduction domain that binds to cargo molecules and transports the cargo molecules into mammalian cells or tissues, the cargo molecule transduction domain comprising:
1) a RMAD1 peptide consisting of SEQ ID NO: 1 derived from human ADARB2; or
2) a RMVAD 1 variant peptide consisting of 8 to 50 amino acids in which one or more amino acids are deleted, substituted, and/or added to the RMVAD 1 peptide.
2. (original) The cargo molecule transduction domain of claim 1, wherein an amino acid substitution in the RMVAD 1 variant peptide is a conservative amino acid substitution, which corresponds to instant claim 2.
3. (currently amended) The cargo molecule transduction domain according to claim 1, wherein the RMVAD1 variant peptide is a sequence in which a lysine residue position of SEQ ID NO: 1 is independently substituted with an arginine residue and/or an arginine residue position of SEQ ID NO: 1 is independently substituted with a lysine residue, which corresponds to instant claim 3.
4. (original) The cargo molecule transduction domain of claim 1, wherein, in a peptide sequence in which one or more amino acids are deleted from the RMAD 1 variant peptide, one to six lysine residues and arginine residues among the amino acids of the RMVAD 1 peptide are deleted, which corresponds to instant claim 4.
5. (original) The cargo molecule transduction domain of claim 1, wherein a peptide sequence in which one or more amino acids are deleted and/or added to the RMAD 1 peptide has amino acid deletions and/or additions in any one or more of an N-terminus and a C-terminus, which corresponds to instant claim 5.
6. (currently amended) The cargo molecule transduction domain according to claim 1,wherein one or more of 1) a RMAD1 peptide consisting of SEQ ID NO: 1 derived from human ADARB2; or 2) a RMAD 1 variant peptide consisting of 8 to 50 amino acids in which one or more amino acids are deleted, substituted, and/or added to the RMAD 1 peptide, is bound in the form of a dimer or higher-order multimer without a linker or through a linker, which corresponds to instant claim 6.
The ADARB2 peptide of SEQ ID NO: 1 in claims of co-pending application No. 18/288,824 consists of the amino acid sequence CKSKRRRRRRSKRKD of SEQ ID NO:1, which is a RMAD1 variant recited in instant claims 1 and 2. The dimer and multimer of the RMAD1 peptide of SEQ ID NO: 1 in claim 6 of co-pending application No. 18/290570 meets the limitations of instant claim 7.
This is a provisional obviousness-type double patenting rejections because the conflicting claims have not in fact been patented.
Allowable Subject Matter
An isolated peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 20 and 22 is free of prior art.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHUONG HUYNH whose telephone number is (571)272-0846. The examiner can normally be reached on 9:00 a.m. to 6:30 p.m. The examiner can also be reached on alternate alternative Friday from 9:00 a.m. to 5:30 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Misook Yu, can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PHUONG HUYNH/ Primary Examiner, Art Unit 1641
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