Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of Application and Claims
US Patent 8,853,179 issued on 10/7/14 from application 13/203,229 with claim 1. This reissue application was filed on 8/20/24 and added new claims 2-48. Claims 1-48 are pending.
Specification
The 8/20/24 amendment to the specification fails to comply with 37 CFR 1.173(b)(1) and (d) because it does not contain the required markings.
The specification of the underlying ’179 patent is objected to because it contains browser-executable code. (See column 22, line 62.) See MPEP 608.01(VII).
Claim Objections
The 8/20/24 claim listing is noncompliant with 37 CFR 1.173(b)(2) because it does not contain status identifiers for each claim (e.g., “Original,” “New”).
The remarks provide information about the support for the new claims, but they do so with relation to published application US 2012/0053333,1 not the underlying ’179 patent. A pre-grant publication of an application does not necessarily have the same content as a patent issuing from that application. For record clarity, applicant should identify the support for new claims within the patent under reissue. This explanation should be provided for all claims in response to this Office action.
Information Disclosure Statement
This application was filed with a single information disclosure statement (IDS). None of the references listed on the IDSes in the underlying 13/203,229 application will appear on the face of a patent issuing from this application unless they are properly listed on an IDS in this application. See MPEP 1406.
Assignee’s Consent to Reissue
The 8/20/24 consent to reissue signed by Thomas Fitting is defective because it was neither signed by a person with apparent authority as defined in MPEP 325(V) nor signed by a person authorized to act on behalf of the assignee at the time of signing. MPEP 325(V) recognizes that persons with “apparent authority” to sign on behalf of an organization include officers of that organization, e.g., its chief executive officer, president, vice-president, secretary, or treasurer. Consenter Fitting is none of these, being designated only as “Chief Patent Counsel.” There is also nothing in the record to indicate that consenter Fitting was authorized to act on behalf of the assignee.
This matter would be overcome by submission of a replacement consent of the assignee signed by either a person authorized to act on behalf of the assignee; an officer of the assignee; or a patent practitioner already appointed power of attorney at the time of signing.
Multiple Reissue Applications
This reissue application is the parent of application 19/083,131. 37 CFR 1.177(a) requires that all multiple reissue applications resulting from a single patent must include as the first sentence of their respective specifications a cross reference to the other reissue application(s). Accordingly, the first sentence of each reissue specification must provide notice stating that more than one reissue application has been filed, and it must identify each of the reissue applications and their relationship within the family of reissue applications, and to the original patent. An example of the suggested language to be inserted is as follows:
Notice: More than one reissue application has been filed for the reissue of Patent No. 99,999,999. The reissue applications are application number 99/999,994 (the present application); and application number 99/999,995, which is a continuation reissue of Patent No. 99,999,999.
See MPEP 1451. In addition to amending the specification of this application, applicant should file a certificate of correction in the underlying ’179 patent to inform the public of the presence of both this application and application 19/083,131.
Election by Original Presentation
37 CFR 1.176(b) permits the examiner to require restriction in a reissue application between claims newly added in a reissue application and the original patent claims where the added claims are directed to an invention that is separate and distinct from the invention(s) defined by the original patent claims. See MPEP 1450.
Applicant may file divisional reissue applications directed to the constructively non-elected inventions. See MPEP 1450.
The reissue application contains claims to three patentably distinct inventions:
A method of improving full-length protein-expression efficiency comprising providing a particular polynucleotide and then mutating one or more secondary initiation codons within it, thereby providing a decrease in initiation of protein synthesis at those codons (claims 1-34 and 44);
A polynucleotide produced by the methods (claims 35-43, 45, and 48); and
A method of treating or preventing clinical symptoms of a disease by providing the polynucleotide of claim 45 to a patient (claims 46 and 47).
The polynucleotides of claims 35-43, 45, and 48 could be made by a different process such as by direct synthesis or cloning of a desired sequence, i.e. a process that does not alter a first polynucleotide to generate a mutated one. Once the desired sequence of the “mutated” polynucleotide is known, it can be produced using conventional molecular-biology techniques. Because this is the case, the treatment/prevention methods of claims 46 and 47 do not require the steps of claims 1-34 and 44.
Claims 35-43 and 45-48 are withdrawn from consideration as being drawn to constructively non-elected inventions. Claims 1-34 and 44 are under examination on their merits.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 12 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 1 recites a method of improving full-length protein-expression efficiency by providing a coding sequence for the full-length protein and mutating secondary initiation codon(s) within it; claim 12 requires that the polynucleotide comprises a single cistron. This limitation functions as a negative limitation in that it excludes polycistronic and multicistronic polynucleotides. “Any negative limitation or exclusionary proviso must have basis in the original disclosure.” MPEP 2173.05(i).
The term “cistron” refers to a stretch of nucleic acid that carries the information for a polypeptide chain. (See Liu et al., US 2006/0018881; reference A, at paragraph 42.) Before the time the invention was made, skilled artisans understood the existence of both monocistronic and polycistronic polynucleotide sequences. Lopez Lastra et al. (2004, US Patent 6,783,977; reference B) explains that in a polycistronic system, multiple transcripts are under the control of a single promoter; a monocistronic system expresses only a single transcript from the promoter. (Column 5, lines 30-34.) Liu likewise observes that a polynucleotide may contain multiple cistrons. (Paragraph 42.) Skilled artisans also understood that generally, eukaryotic genes are monocistronic, while prokaryote genes can be of either type. (See Wilson, 1996, US Patent 5,489,527; reference C, at column 1, lines 14-22.) In addition, skilled artisans appreciated a distinction between vectors and constructs encoding a single protein product and those encoding more than one (“multicistronic” expression cassettes). (See Otte et al., US 2007/0212755, at paragraph 27; reference E.) In light of these teachings, the skilled artisan would have understood claim 12 as excluding polycistronic or multicistronic polynucleotides from the scope of the provided polynucleotide.
The ’179 patent does not provide sufficient basis for excluding polycistronic or multicistronic polynucleotides from the scope of the claims. The word “cistron” appears only six times in the ’179 patent, always in the context of describing the general concept of the term as a unit of protein expression:
“The term ‘cistron’ means a unit of DNA that encodes a single polypeptide or protein.” (Column 4, lines 53-54.)
“The language ‘gene of interest’ is intended to include a cistron, an [ORF], or a polynucleotide sequence which codes for a protein product (protein of interest) whose production is to be modulated.” (Column 4, lines 62-65.)
“An ‘initiation codon’ or ‘initiation triplet’ is the position within a cistron where protein synthesis starts.” (Column 8, lines 10-11.)
“As used herein, ‘authentic initiation codon’ or ‘primary initiation codon’ refers to the initiation codon of a cistron that encodes the first amino acid of the coding sequence of the encoded protein of interest whose production is to be modulated.” (Column 8, lines 35-39.)
“FIGS. 1A-1B show bacterial expression constructs were generated containing the CAT [chloramphenicol acetyltransferase] cistron (CAT) and a partially modified CAT cistron (mCAT) and tested in the E. coli bacterial strain DH5[Symbol font/0x61].” (Column 13, lines 46-49.)
Nowhere does the ’179 patent set forth monocistronic and polycistronic/multicistronic systems as alternatives to each other or otherwise provide support for excluding the latter from the scope of claim 12. The limitation “wherein the polynucleotide comprises a single cistron” therefore does not have sufficient basis in the underlying ’179 patent, so claim 12 must be rejected for lack of written description. See MPEP 2173.05(i) (“Any claim containing a negative limitation which does not have basis in the original disclosure should be rejected under . . . pre-AIA 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.”)
Claim Rejections - 35 USC § 251 (Original Patent)
Claim 12 is rejected under 35 U.S.C. 251 as failing to satisfy the reissue standard of 35 U.S.C. § 251, specifically the requirement that the reissued patent claim the invention disclosed in the original patent.
Under the original patent requirement, “it is not enough that an invention might have been claimed in the original patent because it was suggested or indicated in the specification.” U.S. Indus. Chemicals, Inc. v. Carbide & Carbon Chemicals Corp., 315 U.S. 668, 676 (1942). “Rather, the specification must clearly and unequivocally disclose the newly claimed invention as a separate invention.” Antares Pharma, Inc. v. Medac Pharma Inc., 771 F.3d 1354, 1362 (Fed. Cir. 2014) (citing Industrial Chemicals, 315 U.S. at 676). Furthermore:
The ‘original patent’ standard and the written description requirement are not the same. Where the written description requirement is based on what the skilled artisan would have understood was within the possession of the inventor, recent Federal Circuit case law indicates that the original patent requirement under § 251 requires something more.
MPEP 1412.01(I) (quoting Ex parte Sandwick, Appeal No. 2018-008369, op. at 22 (PTAB July 23, 2019)).
The invention of claim 12 is not clearly and unequivocally disclosed in the underlying patent as a separate invention because the ’179 patent nowhere contemplates an exclusively monocistronic polynucleotide, so the original patent requirement has not been met.
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 24 and 25 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.
Claims 24 and 25 depend from claim 6 and require that the polynucleotide includes a signal-peptide-coding region. Claim 24 goes on to recite, “comprising mutating or removing AUG/ATG codons in the signal peptide coding region of the polynucleotide.” It is unclear how the step within this “comprising” limitation relates to the remaining active steps of the claim. The same is true of claim 25. (Compare claim 26, which makes clear that the miRNA-binding sites are mutated.) Clarification is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1, 2, 13-18, 20-22, 32, and 33 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Weiland (1989, Nucleic Acids Research 17: 4675-4687; NPL reference 4 on 8/20/24 IDS) as evidenced by Osawa et al. (1992, Microbiological Reviews 56: 229-264; reference U).
Weiland teaches a pUC-derived plasmid containing the entire genome of turnip yellow mosaic virus (TYMV). (Abstract; Figure 1.) Weiland teaches that this plasmid, pTMYC, contains two different start codons, one that encodes a 69kDa protein and another that encodes a 206kDa protein. See Figure 1, describing “69kd ORF AUG” and “206kd ORF AUG”:
PNG
media_image1.png
240
566
media_image1.png
Greyscale
Weiland’s 206kd ORF AUG is a secondary initiation codon as the underlying ’179 patent defines it because it is “an initiation codon that is other than the primary or authentic initiation codon for the encoded protein of interest” where the “encoded protein of interest” is the 69kd protein. (See ’179 patent at column 8, lines 39-41.) Weiland’s 206kd AUG (AUG-95) is downstream of the 69kd AUG (AUG-88) and out-of-frame with respect to it. (Figure 1, lower panel.) Weiland teaches mutating the 206kd AUG to ACG. (Figure 1, lower panel, “206ACG” construct.) Weiland teaches that the 206ACG mutant results in enhanced translation of the smaller protein product and loss of expression of the larger one. (Page 4682, last paragraph.) Within the context of the 69kd AUG product, Weiland’s mutation represents AAU [Wingdings font/0xE0] AAC, which Osawa evidences is a silent mutation since both codons encode asparagine. (Table 1 at page 231.) As such, the amino acid sequence of the 69kd AUG product remains unchanged after Weiland’s mutation. Regarding claims 14-16, Weiland demonstrates that expression of the 69kd AUG product is increased; claims 14-16 do not provide any point of reference for the relative term “increased.” Regarding claims 17 and 18, Weiland’s pTYMC places the viral genome under the control of a T7 promoter. (Figure 1, top panel.) Regarding claim 22, Osawa evidences that ACG is not an initiation (start) codon. (Table 1 at page 231, showing that ACG codes for threonine.)
Claims 1, 3, 5, 13-16, 22, 32, and 33 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Sacerdot (1992, Journal of Molecular Biology 225: 67-80; reference V) as evidenced by Osawa et al. (1992, Microbiological Reviews 56: 229-264).
Sacerdot teaches that the IF2 gene of E. coli contains multiple initiation codons including an AUG codon that generates IF2[Symbol font/0x61] and a downstream in-frame GUG codon that generates IF2[Symbol font/0x62]. (Abstract; Figure 1.) Sacerdot’s downstream GUG codon is a secondary initiation codon as the underlying ’179 patent defines it because it is “an initiation codon that is other than the primary or authentic initiation codon for the encoded protein of interest” where the “encoded protein of interest” is IF2[Symbol font/0x61]. (See ’179 patent at column 8, lines 39-41.) Sacerdot teaches that mutating the GUG codon to GUA, GUC, or GUU results in decreased expression of IF2[Symbol font/0x62], i.e. enhanced expression of IF2[Symbol font/0x61] relative to total IF2, from a plasmid vector. (Table 2.) Osawa is cited solely as evidence that mutating GUG to GUA, GUC, or GUU does not change the amino-acid sequence of IF2[Symbol font/0x61] because all four of these combinations code for valine. (Table 1 at page 231.) Regarding claims 14-16, Sacerdot demonstrates increased relative expression of IF2[Symbol font/0x61]; claims 14-16 do not provide any point of reference for the relative term “increased.” Regarding claim 22, Osawa evidences that GUA, GUC, and GUU are not initiation codons because they code for valine.
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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-9, 11, 12, 14-22, 24-31, 33 and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 4-8, 12-14, 20-24, 28-33, 36, 37, 47, and 53 of copending Application No. 19/083,131 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The ’131 application claims a method of improving full-length protein-expression efficiency comprising a polynucleotide encoding a single cistron comprising (i) a coding sequence for the full-length protein, (ii) a primary initiation codon upstream of the coding sequence and encoding the first amino acid of the coding sequence, and (iii) one or more secondary initiation codons located within the coding sequence but downstream of the primary initiation codon. (Claim 2.) This starting material anticipates the starting material of examined claims 1 and 33 because it is one embodiment within the scope. The ’131 application then claims mutating the secondary initiation codon(s) to provide a decrease in protein-synthesis initiation at the secondary codon(s), thereby improving full-length protein-expression efficiency initiated at the primary codon. (Claim 2.) The ’131 application claims that the amino acid sequence of the protein remains unaltered. (Claim 2.) Claim 2 of the ’131 application therefore anticipates examined claims 1 and 33.
Examined claims 2-9 correspond to claims 5, 4, 6, 7, 8, and 28 of the ’131 application. Examined claim 11 corresponds to claim 29 of the ’131 application. Examined claim 12 is anticipated by claim 2 of the ’131 application. Examined claims 14-16 correspond to claims 36 and 37 of the ’131 application and/or their ranges overlap those claimed in ’131 and therefore are rendered obvious over them; see MPEP 2144.05(I). Examined claims 17 and 18 correspond to claims 30 and 31 of the ’131 application, respectively. Examined claim 19 corresponds to claim 12 of the ’131 application. Examined claim 20 corresponds to claim 47 of the ’131 application. Examined claim 22 corresponds to claims 13 and 14 of the ’131 application. Examined claims 24 and 25 correspond to claims 32 and 33 of the ’131 application, respectively. Examined claims 26-31 correspond to claims 20-24 of the ’131 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 32 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 4-8, 12-14, 20-24, 28-33, 36, 37, 47, and 53 of copending Application No. 19/083,131 as applied to claims 1-9, 11, 12, 14-22, 24-31, 33 and 34, above, and further in view of Janulaitis et al. (US 20030040614; reference D).
The claims of the ’131 application are relied upon as above.
The ’131 application does not claim a step of incorporating the mutated polynucleotide into a vector or construct.
Janulaitis teaches mutagenizing polypeptides, then incorporating them into a conventional cloning vector to permit propagation within a host cell. (Paragraph 27, e.g.)
It would have been obvious to incorporate the ’131 application’s mutagenized polynucleotide into a conventional cloning vector because Janulaitis teaches that this step was known for propagating polynucleotides in a host cell.
Relevant Prior Art
The following prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Odjakova et al. (1998, Microbiological Research 153: 173-178; reference W) teaches that the E. coli chloramphenicol acetyltransferase (CAT) gene contains an AUG start codon and two “downstream boxes” from which translation can be initiated. (Abstract; page 174, column 1; Figure 2.) Odjakova teaches mutating the CAT gene such that the downstream boxes are eliminated, specifically by replacing AAUCA with GAUUA and CACCGU with AACUGU, but such that the amino acid sequence of CAT is maintained. (Figure 2, “pP1R9-CAT(-db)” construct; page 176, column 2.) Odjakova teaches, however, that pP1R9-CAT(-db) generates less CAT protein than the same construct containing the downstream boxes (““pP1R9-CAT(+db)””). (Table 1.)
Maintenance Fees
Applicant is reminded of the requirement to pay all applicable maintenance fees on the original patent. See MPEP 1415.01.
Duty to Disclose
Applicant is reminded of the continuing obligation under 37 CFR 1.178(b), to timely apprise the Office of any prior or concurrent proceeding in which Patent No. 8,853,179 is or was involved. These proceedings would include any trial before the Patent Trial and Appeal Board, interferences, reissues, reexaminations, supplemental examinations, and litigation.
Applicant is further reminded of the continuing obligation under 37 CFR 1.56, to timely apprise the Office of any information which is material to patentability of the claims under consideration in this reissue application.
These obligations rest with each individual associated with the filing and prosecution of this application for reissue. See also MPEP §§ 1404, 1442.01 and 1442.04.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lora E Barnhart Driscoll, whose telephone number is (571)272-1928. The examiner can normally be reached M-F 7:00-4:00 p.m. ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Patricia Engle, can be reached at 571-272-6660. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Lora E Barnhart Driscoll/Patent Reexamination Specialist, Art Unit 3991
Conferees:
/KSO/Patent Reexamination Specialist, Art Unit 3991
/Patricia L Engle/SPRS, Art Unit 3991
1 The remarks incorrectly identify the relevant published application as “US20120533333.”
Prosecution Insights