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 1, 57-58, 60, 76, and newly filed 78-92) in the reply filed on February 12, 2026 is acknowledged. Applicants previously canceled claims 3-27, 30-56, 59, 62-63, 68, 70, and 72-75, and now cancel claims 2, 28-29, 61, 64-67, 69, 71, and 77. Claims 1, 57-58, 60, 76, and newly filed 78-92 are pending in this application and are under examination. Non-elected claims 64-67, 69, and 71 are canceled.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed as PCT Patent Application No. PCT/EP2013/003946 on December 30, 2013. It is noted, however, that applicant has not filed a certified copy of the PCT application as required by 37 CFR 1.55. It is noted that the instant application is also listed as a continuation of PCT Patent Application No. PCT/EP2014/003840, which was filed December 30, 2014.
Information Disclosure Statement
The Information Disclosure Statements filed May 14, 2022; March 27, 2023; and February 12, 2026 have been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
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:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, 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.
It is noted that the Sequence Listing Incorporation by Reference paragraph lists the size of the ASCII text file as 133.8 KB, which should be changed to 133,778 bytes.
Specification
The use of the terms OPTI-MEM® at page 145, lines 22 and 26, LIPOFECTAMINE® at line 24, and HIDEX® at page 146, line 1, which is a trade name or a mark used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 57-58 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
The claims recites a cell comprising an artificial nucleic acid molecule. The cell can be a eukaryotic cell, such as a mammalian cell.
The instant specification provides that the cells can be human cells and/or be included in animal models (page 123, lines 14-28). In addition, the claimed artificial nucleic acid can be used for a variety of process, including replication of a vector comprising the artificial nucleic acid, for producing a recombinant protein, or for use in a pharmaceutical composition (page 123, line 30 to page 124, line 6). Thus, the instantly claimed cell can comprise a cell that contains the artificial nucleic acid, which can be used as a pharmaceutical composition for administration to a subject (page 123, line 30 to page 124, line 6).
Thus, claims 57-58 are deemed to encompass human cells and tissues, which are present or intended to be present in a human organism, and which is non-statutory subject matter. As such the recitation of the limitation “isolated” cell would be remedial. See 1077 Off. Gaz. Pat. Office 24 (April 21, 1987).
Claim Objections
Claims 1, 78, and 80 are objected to because of the following informalities:
At claim 1, line 5, “derived” should be changed to “obtained.”
At claim 78, line 5, “derived” should be changed to “obtained.”
At claim 80, line 2, “TOP” should be changed to “5’ terminal oligopyrimidine tract (TOP).”
Appropriate correction is required.
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.
Claims 1, 57-58, 60, 76, and 78-92 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 1 recites the limitation "the 3’-UTR of a human ribosomal gene" in lines 5-6. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “the” be changed to “a.”
Claims 57-58, 60, 76 depend from claim 1, and are therefore included in this rejection.
Claim 78 recites the limitation "the 3’-UTR of a human ribosomal gene" in line 5. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “the” be changed to “a.”
Claims 79-92 depend from claim 78, and are therefore included in this rejection.
Claim Rejections - 35 USC § 103
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.
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.
Claims 1, 57-58, 60, 76, 78, 79, 81-83, and 87-92 are rejected under 35 U.S.C. 103 as being unpatentable over Schlake et al. (9(11) RNA Biology 1319-1330 (October 12, 2012), and cited in the Information Disclosure Statement filed May 14, 2022) in view of Abu Khabar (PCT Patent Application Publication No. WO 2007/068265, published June 21, 2007, and cited in the Information Disclosure Statement filed May 14, 2022).
Regarding claim 1, Schlake discloses synthetic mRNA comprising 3’ untranslated regions (UTRs) in the mRNA (abstract, page 1320, column 2, third paragraph, and page 1321, column 1, third and fourth full paragraphs). Schlake discloses inclusion of an open reading frame, which encodes a protein (page 1321, column 2, second full paragraph). Schlake discloses that the 3’ UTR can be a β-globin UTR (page 1321, column 1, third and fourth full paragraphs). Schlake discloses that destabilizing sequences, such as AU-rich elements should be avoided (page 1320, column 2, third paragraph).
Regarding claims 57-58, Schlake discloses protein production of luciferase in human in vitro cell lines, as well as injection into an animal, which is interpreted as a cell comprising the artificial nucleic acid (lymph nodes and intradermal injection) (page 1321, column 2, paragraphs 5-7). Schlake discloses ex vivo delivery of mRNA vaccines to human cells in a clinical setting (page 1325, column 1, final full paragraph).
Regarding claim 60, Schlake discloses a therapeutic composition comprising the claimed artificial nucleic acid (page 1319, column 2, first full paragraph).
Regarding claim 76, Schlake discloses a therapeutic composition comprising the claimed artificial nucleic acid (page 1319, column 2, first full paragraph). Because a kit is merely a collection of parts, Schlake is deemed to disclose a kit comprising the claimed artificial nucleic acid and pharmaceutical composition comprising the nucleic acid. [I]n a kit containing a set of chemicals and a printed set of instructions for using the chemicals, the instructions are not related to that particular set of chemicals. In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1684 (Fed. Cir. 2004).
Regarding claim 78, Schlake discloses synthetic mRNA comprising 3’ untranslated regions (UTRs) in the mRNA (abstract, page 1320, column 2, third paragraph, and page 1321, column 1, third and fourth full paragraphs). Schlake discloses inclusion of an open reading frame, which encodes a protein (page 1321, column 2, second full paragraph). Schlake discloses that the 3’ UTR can be a β-globin UTR (page 1321, column 1, third and fourth full paragraphs). Schlake discloses that destabilizing sequences, such as AU-rich elements should be avoided (page 1320, column 2, third paragraph).
Regarding claim 79, Schlake further discloses inclusion of a cap (page 1320, column 2, paragraphs 4-6). Schlake discloses the inclusion of a poly(A) tail to enhance translation initiation (page 1321, column 1, second full paragraph).
Regarding claims 87-88, Schlake discloses that cationic lipids provide protection for mRNAs used for intradermal and intravenous injection of antigen-encoding mRNA (page 1323, column 1, first full paragraph).
Regarding claim 89, Schlake discloses that the mRNAs can be used as vaccines and include an adjuvant and an antigen (page 1323, column 1, second full paragraph, page 1325, column 2, first full paragraph, and paragraph bridging pages 1325 and 1326).
Regarding claim 90, Schlake discloses that the antigen can be E6 antigen of human papilloma virus (i.e., an infectious disease antigen) (page 1325, column 1, final full paragraph).
Regarding claim 91, Schlake discloses that the mRNA can include sequences encoding a melanoma antigen, which is interpreted as being pharmaceutical composition (page 1323, column 1, second full paragraph, page 1325, column 2, first full paragraph, and paragraph bridging pages 1325 and 1326).
Schlake fails to disclose or suggest the use of ribosomal protein gene sequences as the 3’ UTR.
Regarding claim 1, Abu Khabar discloses 3’ untranslated regions, which can include a polyadenylation signal, provide for efficient protein expression in mammalian cells (abstract and page 2, final paragraph). Abu Khabar discloses that the 3’ UTRs can be derived from stable mRNAs, such as ribosomal protein genes (page 5, fifth paragraph).
Regarding claim 81, Abu Khabar discloses that the 3’ UTR can comprise a nucleic acid sequence from a gene encoding rpl32 (Table 1).
Regarding claim 82, Abu Khabar discloses a variety of ribosomal protein genes that can be employed, including at least L10, L13a, l8, L15, L13, S2, S11, L14, L5, L10a, S5, P1, S16, large P1, S14, S19, L19, L18, S24, L11, S18, S9, S25, L38, L32, and many others (Table 1).
Regarding claim 83, Abu Khabar discloses that the 3’-UTR can comprise a nucleic acid from a gene encoding RPS9 (Table 1).
Regarding claim 92, Abu Khabar discloses that the 3’-UTR can comprise a nucleic acid from a gene encoding RPS10 (Table 1).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to substitute Abu Khabar’s ribosomal protein gene 3’ for the 3’ UTRs of Schlake because, as disclosed by Abu Khabar, ribosomal protein genes are housekeeping genes and are extremely stable. Thus, substituting Abu Khabar’s ribosomal protein gene 3’ UTRs for Schlake’s globin 3’ UTRs would result in a more stable mRNA for enhanced, stabilized, and/or prolonged protein production. Because both Schlake’s and Abu Khabar’s 3’ UTRs are well known, one of ordinary skill in the art would have a predictable and reasonable expectation of success in substituting one well known UTR for another.
Claim 80 is rejected under 35 U.S.C. 103 as being unpatentable over Schlake in view of Abu Khabar, as applied to claims 1, 57-58, 60, 76, 78, 79, 81-83, and 87-92 above, and further in view of Mignone et al. (3(3) Genome Biology 1-10 (2002), and cited in the Information Disclosure Statement filed May 14, 2022).
Schlake and Abu Khabar disclose and suggest an artificial nucleic acid molecule, as discussed above.
Schlake and Abu Khabar fail to disclose or suggest that the 5-UTR is a TOP 5’-UTR.
Regarding claim 80, Mignone discloses that the untranslated regions of mRNAs control translation, degradation, and localization of the nucleic acid, and can include stem-loop structures, upstream elements, internal ribosome entry sites (abstract). Mignone discloses that the 5’-TOP element is contained in ribosomal proteins (page 6, column 1, first full paragraph).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to include Mignone’s 5’-TOP UTR element in the mRNA construct of Schlake and Abu Khabar because, as disclosed by Abu Khabar, ribosomal protein genes are housekeeping genes and are extremely stable. Thus, including Mignone’s 5’-TOP UTR element in the mRNA construct of Schlake and Abu Khabar, or encoded for by Abu Khabar’s DNA vector, would result in a more stable mRNA for enhanced, stabilized, and/or prolonged protein production.
Claims 84-86 are rejected under 35 U.S.C. 103 as being unpatentable over Schlake in view of Abu Khabar, as applied to claims 1, 57-58, 60, 76, 78, 79, 81-83, and 87-92 above, and further in view of Trinklein et al. (U.S. Patent Application Publication No. 2008/0220983, published September 11, 2008).
Schlake and Abu Khabar disclose and suggest an artificial nucleic acid molecule, as discussed above.
Schlake and Abu Khabar fail to disclose or suggest a 3’-UTR having a sequence having 90%, 95%, or 100% identity with SEQ ID NO: 58.
Regarding claims 84-86, Trinklein discloses libraries of expression constructs that have a variety of untranslated regions (UTRs) (abstract). Trinklein discloses 3’-UTRs that affect the translation of a reporter gene/open reading frame (abstract). Trinklein discloses that the UTR can be in an mRNA transcript (paragraph [0005]). Trinklein discloses the UTR elements have the sequence of instant SEQ ID NO: 8366, which has 100% identity with instant SEQ ID NO: 58, which encompasses sequences having at least 90%, 95%, and 100% sequence identity with instant SEQ ID NO: 58 (paragraph [0017] and SEQ ID NO: 8366) (Appendix I).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to substitute Trinklein’s ribosomal protein gene 3’ for the 3’ UTRs of Abu Khabar and Schlake because, as disclosed by Abu Khabar, ribosomal protein genes are housekeeping genes and are extremely stable. Thus, substituting Trinklein’s ribosomal protein gene 3’ UTRs for Abu Khabar’s ribosomal 3’-UTR or Schlake’s globin 3’ UTRs would result in a more stable mRNA for enhanced, stabilized, and/or prolonged protein production. Because each of Schlake’s, Abu Khabar’s, and Trinklein’s 3’ UTRs are well known, one of ordinary skill in the art would have a predictable and reasonable expectation of success in substituting one well known UTR for another.
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 57-58, 60, 76, and 78-92 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7-10, 12-14, 17, and 19-21 of U.S. Patent No. 9,683,233 in view of Abu Khabar (PCT Patent Application Publication No. WO 2007/068265, published June 21, 2007, and cited in the Information Disclosure Statement filed May 14, 2022), Mignone et al. (3(3) Genome Biology 1-10 (2002), and cited in the Information Disclosure Statement filed May 14, 2022) and Trinklein et al. (U.S. Patent Application Publication No. 2008/0220983, published September 11, 2008).
The ‘233 patent claims a method of expressing a polypeptide in a subject by administering an artificial nucleic acid that includes an open reading frame, a 5’-TOP UTR, and a 3’-UTR albumin to provide a stable mRNA. The ‘233 patent further claims that the TOP gene can be a ribosomal protein, including RPL32. The ‘233 patent discloses SEQ ID NO: 1394, which is identical to instant SEQ ID NO: 5. The ‘233 patent claims that the molecule can be a DNA or an RNA.
The ‘233 patent fails to claim that the 3’-UTR is a UTR from a ribosomal protein gene. The ‘233 patent fails to claim additional and specific ribosomal protein 3’-UTRs.
Regarding claim 1, Abu Khabar discloses 3’ untranslated regions, which can include a polyadenylation signal, provide for efficient protein expression in mammalian cells (abstract and page 2, final paragraph). Abu Khabar discloses that the 3’ UTRs can be derived from stable mRNAs, such as ribosomal protein genes (page 5, fifth paragraph).
Regarding claim 81, Abu Khabar discloses that the 3’ UTR can comprise a nucleic acid sequence from a gene encoding rpl32 (Table 1).
Regarding claim 82, Abu Khabar discloses a variety of ribosomal protein genes that can be employed, including at least L10, L13a, l8, L15, L13, S2, S11, L14, L5, L10a, S5, P1, S16, large P1, S14, S19, L19, L18, S24, L11, S18, S9, S25, L38, L32, and many others (Table 1).
Regarding claim 83, Abu Khabar discloses that the 3’-UTR can comprise a nucleic acid from a gene encoding RPS9 (Table 1).
Regarding claim 92, Abu Khabar discloses that the 3’-UTR can comprise a nucleic acid from a gene encoding RPS10 (Table 1).
Regarding claim 80, Mignone discloses that the untranslated regions of mRNAs control translation, degradation, and localization of the nucleic acid, and can include stem-loop structures, upstream elements, internal ribosome entry sites (abstract). Mignone discloses that the 5’-TOP element is contained in ribosomal proteins (page 6, column 1, first full paragraph).
Regarding claims 84-86, Trinklein discloses libraries of expression constructs that have a variety of untranslated regions (UTRs) (abstract). Trinklein discloses 3’-UTRs that affect the translation of a reporter gene/open reading frame (abstract). Trinklein discloses that the UTR can be in an mRNA transcript (paragraph [0005]). Trinklein discloses the UTR elements have the sequence of instant SEQ ID NO: 8366, which has 100% identity with instant SEQ ID NO: 58, which encompasses sequences having at least 90%, 95%, and 100% sequence identity with instant SEQ ID NO: 58 (paragraph [0017] and SEQ ID NO: 8366) (Appendix I).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to substitute Abu Khabar’s ribosomal protein gene 3’-UTR or Trinklein’s 3’-UTR, as well as 5’-UTRs of Mignone, for the 3’ and 5’ UTRs of the ‘233 patent because, as disclosed by Abu Khabar, Mignone, and Trinklein, ribosomal protein genes are housekeeping genes and are extremely stable. Thus, substituting Abu Khabar’s and Trinklein’s ribosomal protein gene 3’-UTRs and Mignone’s 5’ UTRs for the ‘233 patent’s 3’ albumin UTR would result in a more stable mRNA for enhanced, stabilized, and/or prolonged protein production. Because the ‘233 patent’s, Abu Khabar’s 5’ and 3’ UTRs, Trinklein’s 3’-UTRs and Mignone’s 5’ UTR are well known, one of ordinary skill in the art would have a predictable and reasonable expectation of success in substituting one well known UTR for another. Further, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘233 patent could be used to enhance, stabilize, and/or prolong protein production because the nucleic acid components of the ‘233 patent, Abu Khabar, Mignone, Trinklein and the instant application are the same, and therefore the result of stabilization, enhancement, and/or prolongation of protein production would be expected to be increased.
Claims 1, 57-58, 60, 76, and 78-92 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7-9, 12, 14, and 17 of U.S. Patent No. 10,080,809 in view of Abu Khabar (PCT Patent Application Publication No. WO 2007/068265, published June 21, 2007, and cited in the Information Disclosure Statement filed May 14, 2022) and Mignone et al. (3(3) Genome Biology 1-10 (2002), and cited in the Information Disclosure Statement filed May 14, 2022) and Trinklein et al. (U.S. Patent Application Publication No. 2008/0220983, published September 11, 2008).
The ‘809 patent claims a method of expressing a polypeptide in a subject by administering an artificial nucleic acid that includes an open reading frame, a 5’-TOP UTR, and a 3’-UTR albumin to provide a stable mRNA. The ‘809 patent further claims that the TOP gene can be a ribosomal protein, including RPL32. The ‘809 patent discloses SEQ ID NO: 1394, which is identical to instant SEQ ID NO: 5. The ‘809 patent claims that the molecule can be a DNA or an RNA.
The ‘809 patent fails to claim that the 3’-UTR is a UTR from a ribosomal protein gene. The ‘809 patent fails to claim additional and specific ribosomal protein 3’-UTRs.
Regarding claim 1, Abu Khabar discloses 3’ untranslated regions, which can include a polyadenylation signal, provide for efficient protein expression in mammalian cells (abstract and page 2, final paragraph). Abu Khabar discloses that the 3’ UTRs can be derived from stable mRNAs, such as ribosomal protein genes (page 5, fifth paragraph).
Regarding claim 81, Abu Khabar discloses that the 3’ UTR can comprise a nucleic acid sequence from a gene encoding rpl32 (Table 1).
Regarding claim 82, Abu Khabar discloses a variety of ribosomal protein genes that can be employed, including at least L10, L13a, l8, L15, L13, S2, S11, L14, L5, L10a, S5, P1, S16, large P1, S14, S19, L19, L18, S24, L11, S18, S9, S25, L38, L32, and many others (Table 1).
Regarding claim 83, Abu Khabar discloses that the 3’-UTR can comprise a nucleic acid from a gene encoding RPS9 (Table 1).
Regarding claim 92, Abu Khabar discloses that the 3’-UTR can comprise a nucleic acid from a gene encoding RPS10 (Table 1).
Regarding claim 80, Mignone discloses that the untranslated regions of mRNAs control translation, degradation, and localization of the nucleic acid, and can include stem-loop structures, upstream elements, internal ribosome entry sites (abstract). Mignone discloses that the 5’-TOP element is contained in ribosomal proteins (page 6, column 1, first full paragraph).
Regarding claims 84-86, Trinklein discloses libraries of expression constructs that have a variety of untranslated regions (UTRs) (abstract). Trinklein discloses 3’-UTRs that affect the translation of a reporter gene/open reading frame (abstract). Trinklein discloses that the UTR can be in an mRNA transcript (paragraph [0005]). Trinklein discloses the UTR elements have the sequence of instant SEQ ID NO: 8366, which has 100% identity with instant SEQ ID NO: 58, which encompasses sequences having at least 90%, 95%, and 100% sequence identity with instant SEQ ID NO: 58 (paragraph [0017] and SEQ ID NO: 8366) (Appendix I).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to substitute Abu Khabar’s ribosomal protein gene 3’-UTR or Trinklein’s 3’-UTR, as well as 5’-UTRs of Mignone, for the 3’ and 5’ UTRs of the ‘809 patent because, as disclosed by Abu Khabar, Mignone, and Trinklein, ribosomal protein genes are housekeeping genes and are extremely stable. Thus, substituting Abu Khabar’s and Trinklein’s ribosomal protein gene 3’-UTRs and Mignone’s 5’ UTRs for the ‘809 patent’s 3’ albumin UTR would result in a more stable mRNA for enhanced, stabilized, and/or prolonged protein production. Because the ‘809 patent’s, Abu Khabar’s 5’ and 3’ UTRs, Trinklein’s 3’-UTRs and Mignone’s 5’ UTR are well known, one of ordinary skill in the art would have a predictable and reasonable expectation of success in substituting one well known UTR for another. Further, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘809 patent could be used to enhance, stabilize, and/or prolong protein production because the nucleic acid components of the ‘809 patent, Abu Khabar, Mignone, Trinklein and the instant application are the same, and therefore the result of stabilization, enhancement, and/or prolongation of protein production would be expected to be increased.
Claims 1, 57-58, 60, 76, and 78-83, and 87-92 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 and 19-20 of U.S. Patent No. 11,254,951.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘951 patent and the instant application claim an artificial nucleic acid comprising an open reading frame that does not encode a ribosomal protein and at least one 3’-UTR that is derived from a ribosomal protein gene. The ‘951 patent and the instant application claim cells comprising the artificial nucleic acid. The ‘951 patent and the instant application claim a pharmaceutical composition comprising the nucleic acid molecule. The ‘951 patent and the instant application claim that the nucleic acid is an mRNA. The ‘951 patent and the instant application claim a 5’ Cap and a poly(A) sequence. the ‘951 patent and the instant application claim specific ribosomal 3’UTRs that are the same. The ‘951 patent and the instant application claim that the RNA is complexed with a cationic or polycationic lipid. The ‘951 patent and the instant application claim that the ORF encodes an antigen that may be an infectious disease antigen or a tumor antigen. The ‘951 patent and the instant application claim a kit comprising the nucleic acid molecule and instructions for use.
Therefore, the claims are not deemed to be patentably distinct.
Claims 84-86 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 and 19-20 of U.S. Patent No. 11,254,951 in view of Trinklein et al. (U.S. Patent Application Publication No. 2008/0220983, published September 11, 2008).
The ‘951 patent claims an artificial nucleic acid molecule, as discussed above.
The ‘951 patent fails to claim that the 3’-UTR has a sequence that has 90%, 95%, or 100% identity to instant SEQ ID NO: 58.
Regarding claims 84-86, Trinklein discloses libraries of expression constructs that have a variety of untranslated regions (UTRs) (abstract). Trinklein discloses 3’-UTRs that affect the translation of a reporter gene/open reading frame (abstract). Trinklein discloses that the UTR can be in an mRNA transcript (paragraph [0005]). Trinklein discloses the UTR elements have the sequence of instant SEQ ID NO: 8366, which has 100% identity with instant SEQ ID NO: 58, which encompasses sequences having at least 90%, 95%, and 100% sequence identity with instant SEQ ID NO: 58 (paragraph [0017] and SEQ ID NO: 8366) (Appendix I).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to substitute Trinklein’s ribosomal protein gene 3’ for the 3’ UTRs of the ‘951 patent, because ribosomal protein genes are housekeeping genes and are extremely stable. Thus, substituting Trinklein’s ribosomal protein gene 3’ UTRs for the ‘951 patent’s ribosomal 3’-UTR would result in a more stable mRNA for enhanced, stabilized, and/or prolonged protein production. Because each of the ‘951 patent’s and Trinklein’s 3’ UTRs are well known, one of ordinary skill in the art would have a predictable and reasonable expectation of success in substituting one well known UTR for another.
Claims 1, 57-58, 60, 76, and 78-92 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,286,492 in view of Abu Khabar (PCT Patent Application Publication No. WO 2007/068265, published June 21, 2007, and cited in the Information Disclosure Statement filed May 14, 2022), Mignone et al. (3(3) Genome Biology 1-10 (2002), and cited in the Information Disclosure Statement filed May 14, 2022) and Trinklein et al. (U.S. Patent Application Publication No. 2008/0220983, published September 11, 2008).
The ‘492 patent claims a method of expressing a polypeptide in a subject by administering an artificial nucleic acid that includes an open reading frame, a 5’-TOP UTR, and a 3’-UTR albumin to provide a stable mRNA. The ‘492 patent further claims that the TOP gene can be a ribosomal protein, including RPL32. The ‘492 patent claims that the molecule can be a DNA or an RNA.
The ‘492 patent fails to claim that the 3’-UTR is a UTR from a ribosomal protein gene. The ‘492 fails to claim additional and specific ribosomal protein 3’-UTRs.
Regarding claim 1, Abu Khabar discloses 3’ untranslated regions, which can include a polyadenylation signal, provide for efficient protein expression in mammalian cells (abstract and page 2, final paragraph). Abu Khabar discloses that the 3’ UTRs can be derived from stable mRNAs, such as ribosomal protein genes (page 5, fifth paragraph).
Regarding claim 81, Abu Khabar discloses that the 3’ UTR can comprise a nucleic acid sequence from a gene encoding rpl32 (Table 1).
Regarding claim 82, Abu Khabar discloses a variety of ribosomal protein genes that can be employed, including at least L10, L13a, l8, L15, L13, S2, S11, L14, L5, L10a, S5, P1, S16, large P1, S14, S19, L19, L18, S24, L11, S18, S9, S25, L38, L32, and many others (Table 1).
Regarding claim 83, Abu Khabar discloses that the 3’-UTR can comprise a nucleic acid from a gene encoding RPS9 (Table 1).
Regarding claim 92, Abu Khabar discloses that the 3’-UTR can comprise a nucleic acid from a gene encoding RPS10 (Table 1).
Regarding claim 80, Mignone discloses that the untranslated regions of mRNAs control translation, degradation, and localization of the nucleic acid, and can include stem-loop structures, upstream elements, internal ribosome entry sites (abstract). Mignone discloses that the 5’-TOP element is contained in ribosomal proteins (page 6, column 1, first full paragraph).
Regarding claims 84-86, Trinklein discloses libraries of expression constructs that have a variety of untranslated regions (UTRs) (abstract). Trinklein discloses 3’-UTRs that affect the translation of a reporter gene/open reading frame (abstract). Trinklein discloses that the UTR can be in an mRNA transcript (paragraph [0005]). Trinklein discloses the UTR elements have the sequence of instant SEQ ID NO: 8366, which has 100% identity with instant SEQ ID NO: 58, which encompasses sequences having at least 90%, 95%, and 100% sequence identity with instant SEQ ID NO: 58 (paragraph [0017] and SEQ ID NO: 8366) (Appendix I).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to substitute Abu Khabar’s ribosomal protein gene 3’-UTR or Trinklein’s 3’-UTR, as well as 5’-UTRs of Mignone, for the 3’ and 5’ UTRs of the ‘492 patent because, as disclosed by Abu Khabar, Mignone, and Trinklein, ribosomal protein genes are housekeeping genes and are extremely stable. Thus, substituting Abu Khabar’s and Trinklein’s ribosomal protein gene 3’-UTRs and Mignone’s 5’ UTRs for the ‘492 patent’s 3’ albumin UTR would result in a more stable mRNA for enhanced, stabilized, and/or prolonged protein production. Because the ‘492 patent’s, Abu Khabar’s 5’ and 3’ UTRs, Trinklein’s 3’-UTRs and Mignone’s 5’ UTR are well known, one of ordinary skill in the art would have a predictable and reasonable expectation of success in substituting one well known UTR for another. Further, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘492 patent could be used to enhance, stabilize, and/or prolong protein production because the nucleic acid components of the ‘492 patent, Abu Khabar, Mignone, Trinklein and the instant application are the same, and therefore the result of stabilization, enhancement, and/or prolongation of protein production would be expected to be increased.
Claims 1, 57-58, 60, 76, and 78-92 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-7, 11-14, and 17 of U.S. Patent No. 11,761,009 in view of Abu Khabar (PCT Patent Application Publication No. WO 2007/068265, published June 21, 2007, and cited in the Information Disclosure Statement filed May 14, 2022), Mignone et al. (3(3) Genome Biology 1-10 (2002), and cited in the Information Disclosure Statement filed May 14, 2022) and Trinklein et al. (U.S. Patent Application Publication No. 2008/0220983, published September 11, 2008).
The ‘009 patent claims a method of expressing a polypeptide in a subject by administering an artificial nucleic acid that includes an open reading frame, a 5’-TOP UTR, and a 3’-UTR albumin to provide a stable mRNA. The ‘009 patent further claims that the TOP gene can be a ribosomal protein, including RPL32. The ‘009 patent claims that the molecule can be a DNA or an RNA.
The ‘009 patent fails to claim that the 3’-UTR is a UTR from a ribosomal protein gene. The ‘009 fails to claim additional and specific ribosomal protein 3’-UTRs.
Regarding claim 1, Abu Khabar discloses 3’ untranslated regions, which can include a polyadenylation signal, provide for efficient protein expression in mammalian cells (abstract and page 2, final paragraph). Abu Khabar discloses that the 3’ UTRs can be derived from stable mRNAs, such as ribosomal protein genes (page 5, fifth paragraph).
Regarding claim 81, Abu Khabar discloses that the 3’ UTR can comprise a nucleic acid sequence from a gene encoding rpl32 (Table 1).
Regarding claim 82, Abu Khabar discloses a variety of ribosomal protein genes that can be employed, including at least L10, L13a, l8, L15, L13, S2, S11, L14, L5, L10a, S5, P1, S16, large P1, S14, S19, L19, L18, S24, L11, S18, S9, S25, L38, L32, and many others (Table 1).
Regarding claim 83, Abu Khabar discloses that the 3’-UTR can comprise a nucleic acid from a gene encoding RPS9 (Table 1).
Regarding claim 92, Abu Khabar discloses that the 3’-UTR can comprise a nucleic acid from a gene encoding RPS10 (Table 1).
Regarding claim 80, Mignone discloses that the untranslated regions of mRNAs control translation, degradation, and localization of the nucleic acid, and can include stem-loop structures, upstream elements, internal ribosome entry sites (abstract). Mignone discloses that the 5’-TOP element is contained in ribosomal proteins (page 6, column 1, first full paragraph).
Regarding claims 84-86, Trinklein discloses libraries of expression constructs that have a variety of untranslated regions (UTRs) (abstract). Trinklein discloses 3’-UTRs that affect the translation of a reporter gene/open reading frame (abstract). Trinklein discloses that the UTR can be in an mRNA transcript (paragraph [0005]). Trinklein discloses the UTR elements have the sequence of instant SEQ ID NO: 8366, which has 100% identity with instant SEQ ID NO: 58, which encompasses sequences having at least 90%, 95%, and 100% sequence identity with instant SEQ ID NO: 58 (paragraph [0017] and SEQ ID NO: 8366) (Appendix I).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to substitute Abu Khabar’s ribosomal protein gene 3’-UTR or Trinklein’s 3’-UTR, as well as 5’-UTRs of Mignone, for the 3’ and 5’ UTRs of the ‘009 patent because, as disclosed by Abu Khabar, Mignone, and Trinklein, ribosomal protein genes are housekeeping genes and are extremely stable. Thus, substituting Abu Khabar’s and Trinklein’s ribosomal protein gene 3’-UTRs and Mignone’s 5’ UTRs for the ‘009 patent’s 3’ albumin UTR would result in a more stable mRNA for enhanced, stabilized, and/or prolonged protein production. Because the ‘009 patent’s, Abu Khabar’s 5’ and 3’ UTRs, Trinklein’s 3’-UTRs and Mignone’s 5’ UTR are well known, one of ordinary skill in the art would have a predictable and reasonable expectation of success in substituting one well known UTR for another. Further, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘009 patent could be used to enhance, stabilize, and/or prolong protein production because the nucleic acid components of the ‘009 patent, Abu Khabar, Mignone, Trinklein and the instant application are the same, and therefore the result of stabilization, enhancement, and/or prolongation of protein production would be expected to be increased.
Claims 1, 57-58, 60, 76, and 78-92 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 7, 12-14, and 20-21 of U.S. Patent No. 12,442,005 in view of Abu Khabar (PCT Patent Application Publication No. WO 2007/068265, published June 21, 2007, and cited in the Information Disclosure Statement filed May 14, 2022) and Mignone et al. (3(3) Genome Biology 1-10 (2002), and cited in the Information Disclosure Statement filed May 14, 2022) and Trinklein et al. (U.S. Patent Application Publication No. 2008/0220983, published September 11, 2008).
The ‘005 patent claims a method of expressing a polypeptide in a subject by administering an artificial nucleic acid that includes an open reading frame, and a 3’-UTR albumin to provide a stable mRNA. The ‘005 patent further claims that the TOP gene can be a ribosomal protein, including RPL32. The ‘005 patent claims that the molecule can be a DNA or an RNA.
The ‘005 patent fails to claim that the 3’-UTR is a UTR from a ribosomal protein gene. The ‘005 patent fails to claim additional and specific ribosomal protein 3’-UTRs. The ‘005 patent fails to claim that the 5’-UTR is a 5’-TOP UTR.
Regarding claim 1, Abu Khabar discloses 3’ untranslated regions, which can include a polyadenylation signal, provide for efficient protein expression in mammalian cells (abstract and page 2, final paragraph). Abu Khabar discloses that the 3’ UTRs can be derived from stable mRNAs, such as ribosomal protein genes (page 5, fifth paragraph).
Regarding claim 81, Abu Khabar discloses that the 3’ UTR can comprise a nucleic acid sequence from a gene encoding rpl32 (Table 1).
Regarding claim 82, Abu Khabar discloses a variety of ribosomal protein genes that can be employed, including at least L10, L13a, l8, L15, L13, S2, S11, L14, L5, L10a, S5, P1, S16, large P1, S14, S19, L19, L18, S24, L11, S18, S9, S25, L38, L32, and many others (Table 1).
Regarding claim 83, Abu Khabar discloses that the 3’-UTR can comprise a nucleic acid from a gene encoding RPS9 (Table 1).
Regarding claim 92, Abu Khabar discloses that the 3’-UTR can comprise a nucleic acid from a gene encoding RPS10 (Table 1).
Regarding claim 80, Mignone discloses that the untranslated regions of mRNAs control translation, degradation, and localization of the nucleic acid, and can include stem-loop structures, upstream elements, internal ribosome entry sites (abstract). Mignone discloses that the 5’-TOP element is contained in ribosomal proteins (page 6, column 1, first full paragraph).
Regarding claims 84-86, Trinklein discloses libraries of expression constructs that have a variety of untranslated regions (UTRs) (abstract). Trinklein discloses 3’-UTRs that affect the translation of a reporter gene/open reading frame (abstract). Trinklein discloses that the UTR can be in an mRNA transcript (paragraph [0005]). Trinklein discloses the UTR elements have the sequence of instant SEQ ID NO: 8366, which has 100% identity with instant SEQ ID NO: 58, which encompasses sequences having at least 90%, 95%, and 100% sequence identity with instant SEQ ID NO: 58 (paragraph [0017] and SEQ ID NO: 8366) (Appendix I).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to substitute Abu Khabar’s ribosomal protein gene 3’-UTR or Trinklein’s 3’-UTR, as well as 5’-UTRs of Mignone, for the 3’ and 5’ UTRs of the ‘005 patent because, as disclosed by Abu Khabar, Mignone, and Trinklein, ribosomal protein genes are housekeeping genes and are extremely stable. Thus, substituting Abu Khabar’s and Trinklein’s ribosomal protein gene 3’-UTRs and Mignone’s 5’ UTRs for the ‘005 patent’s 3’ albumin UTR would result in a more stable mRNA for enhanced, stabilized, and/or prolonged protein production. Because the ‘005 patent’s, Abu Khabar’s 5’ and 3’ UTRs, Trinklein’s 3’-UTRs and Mignone’s 5’ UTR are well known, one of ordinary skill in the art would have a predictable and reasonable expectation of success in substituting one well known UTR for another. Further, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘005 patent could be used to enhance, stabilize, and/or prolong protein production because the nucleic acid components of the ‘005 patent, Abu Khabar, Mignone, Trinklein and the instant application are the same, and therefore the result of stabilization, enhancement, and/or prolongation of protein production would be expected to be increased.
Claims 1, 57-58, 60, 76, and 78-92 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-6, 11-12, and 18 of U.S. Patent No. 12,460,204 in view of Abu Khabar (PCT Patent Application Publication No. WO 2007/068265, published June 21, 2007, and cited in the Information Disclosure Statement filed May 14, 2022) and Mignone et al. (3(3) Genome Biology 1-10 (2002), and cited in the Information Disclosure Statement filed May 14, 2022) and Trinklein et al. (U.S. Patent Application Publication No. 2008/0220983, published September 11, 2008).
The ‘204 patent claims a method of expressing a polypeptide in a subject by administering an artificial nucleic acid that includes an open reading frame, and a 3’-UTR albumin to provide a stable mRNA. The ‘204 patent further claims that the TOP gene can be a ribosomal protein, including RPL32. The ‘204 patent claims that the molecule can be a DNA or an RNA.
The ‘204 patent fails to claim that the 3’-UTR is a UTR from a ribosomal protein gene. The ‘204 patent fails to claim additional and specific ribosomal protein 3’-UTRs. The ‘204 patent fails to claim that the 5’-UTR is a 5’-TOP UTR.
Regarding claim 1, Abu Khabar discloses 3’ untranslated regions, which can include a polyadenylation signal, provide for efficient protein expression in mammalian cells (abstract and page 2, final paragraph). Abu Khabar discloses that the 3’ UTRs can be derived from stable mRNAs, such as ribosomal protein genes (page 5, fifth paragraph).
Regarding claim 81, Abu Khabar discloses that the 3’ UTR can comprise a nucleic acid sequence from a gene encoding rpl32 (Table 1).
Regarding claim 82, Abu Khabar discloses a variety of ribosomal protein genes that can be employed, including at least L10, L13a, l8, L15, L13, S2, S11, L14, L5, L10a, S5, P1, S16, large P1, S14, S19, L19, L18, S24, L11, S18, S9, S25, L38, L32, and many others (Table 1).
Regarding claim 83, Abu Khabar discloses that the 3’-UTR can comprise a nucleic acid from a gene encoding RPS9 (Table 1).
Regarding claim 92, Abu Khabar discloses that the 3’-UTR can comprise a nucleic acid from a gene encoding RPS10 (Table 1).
Regarding claim 80, Mignone discloses that the untranslated regions of mRNAs control translation, degradation, and localization of the nucleic acid, and can include stem-loop structures, upstream elements, internal ribosome entry sites (abstract). Mignone discloses that the 5’-TOP element is contained in ribosomal proteins (page 6, column 1, first full paragraph).
Regarding claims 84-86, Trinklein discloses libraries of expression constructs that have a variety of untranslated regions (UTRs) (abstract). Trinklein discloses 3’-UTRs that affect the translation of a reporter gene/open reading frame (abstract). Trinklein discloses that the UTR can be in an mRNA transcript (paragraph [0005]). Trinklein discloses the UTR elements have the sequence of instant SEQ ID NO: 8366, which has 100% identity with instant SEQ ID NO: 58, which encompasses sequences having at least 90%, 95%, and 100% sequence identity with instant SEQ ID NO: 58 (paragraph [0017] and SEQ ID NO: 8366) (Appendix I).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to substitute Abu Khabar’s ribosomal protein gene 3’-UTR or Trinklein’s 3’-UTR, as well as 5’-UTRs of Mignone, for the 3’ and 5’ UTRs of the ‘204 patent because, as disclosed by Abu Khabar, Mignone, and Trinklein, ribosomal protein genes are housekeeping genes and are extremely stable. Thus, substituting Abu Khabar’s and Trinklein’s ribosomal protein gene 3’-UTRs and Mignone’s 5’ UTRs for the ‘204 patent’s 3’ albumin UTR would result in a more stable mRNA for enhanced, stabilized, and/or prolonged protein production. Because the 204 patent’s, Abu Khabar’s 5’ and 3’ UTRs, Trinklein’s 3’-UTRs and Mignone’s 5’ UTR are well known, one of ordinary skill in the art would have a predictable and reasonable expectation of success in substituting one well known UTR for another. Further, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘204 patent could be used to enhance, stabilize, and/or prolong protein production because the nucleic acid components of the ‘204 patent, Abu Khabar, Mignone, Trinklein and the instant application are the same, and therefore the result of stabilization, enhancement, and/or prolongation of protein production would be expected to be increased.
Conclusion
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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636