DETAILED ACTION
Claims 1-92 were/stand cancelled. Claims 93-111 are pending.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (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.
Priority
This application is a CON of 16/577,734 (09/20/2019; PAT 11,564,998) which is a CON of 15/425,645 (02/06/2017; PAT 10,463,751) which is a CON of 15/042,173 (02/12/2016; PAT 9,572,897) which is a CON of 14/390,098 (10/02/2014; PAT 9,303,079) which is a 371 of PCT/US13/30066 (03/09/2013) which claims benefit of 61/618,862 (04/02/2012) and claims benefit of 61/618,866 (04/02/2012) and claims benefit of 61/618,868 (04/02/2012) and claims benefit of 61/618,870 (04/02/2012) and claims benefit of 61/618,873 (04/02/2012) and claims benefit of 61/618,878 (04/02/2012) and claims benefit of 61/618,885 (04/02/2012) and claims benefit of 61/618,896 (04/02/2012) and claims benefit of 61/618,911 (04/02/2012) and claims benefit of 61/618,922 (04/02/2012) and claims benefit of 61/618,935 (04/02/2012) and claims benefit of 61/618,945 (04/02/2012) and claims benefit of 61/618,953 (04/02/2012) and claims benefit of 61/618,961 (04/02/2012) and claims benefit of 61/618,957 (04/02/2012) and claims benefit of 61/648,286 (04/02/2012) and claims benefit of 61/648,244 (04/02/2012) and claims benefit of 61/668,157 (04/02/2012) and claims benefit of 61/681,650 (08/10/2012) and claims benefit of 61/681,667 (08/10/2012) and claims benefit of 61/681,675 (08/10/2012) and claims benefit of 61/681,648 (08/10/2012) and claims benefit of 61/681,687 08/10/20(08/10/2012) 12 and claims benefit of 61/681,654 (08/10/2012) and claims benefit of 61/681,696 (08/10/2012) and claims benefit of 61/681,647 (08/10/2012) and claims benefit of 61/681,704 (08/10/2012) and claims benefit of 61/681,720 (08/10/2012) and claims benefit of 61/681,742 (08/10/2012) and claims benefit of 61/681,658 (08/10/2012) and claims benefit of 61/681,649 (08/10/2012) and claims benefit of 61/681,645 (08/10/2012) and claims benefit of 61/681,661 (08/10/2012) and claims benefit of 61/681,712 (08/10/2012) and claims benefit of 61/696,381 (09/04/2012) and claims benefit of 61/709,303 (10/03/2012) and claims benefit of 61/712,490 (10/11/2012) and claims benefit of 61/737,168 (12/14/2012) and claims benefit of 61/737,203 (12/14/2012) and claims benefit of 61/737,155 (12/14/2012) and claims benefit of 61/737,213 (12/14/2012) and claims benefit of 61/737,139 (12/14/2012) and claims benefit of 61/737,174 (12/14/2012) and claims benefit of 61/737,135 (12/14/2012) and claims benefit of 61/737,152 (12/14/2012) and claims benefit of 61/737,184 (12/14/2012) and claims benefit of 61/737,160 (12/14/2012) and claims benefit of 61/737,130 (12/14/2012) and claims benefit of 61/737,191 (12/14/2012) and claims benefit of 61/737,134 (12/14/2012) and claims benefit of 61/737,147 (12/14/2012) as reflected in the filing receipt issued November 22 2023.
Claim Objections
Claim 93 is objected to because of the following informalities: the acronym “UTR” is not defined in the claims. When an acronym is used in a claim set, it should be defined the first time it appears in the claims. For the purposes of examination, the term “UTR” is interpreted to mean untranslated region. Appropriate correction is required.
Claim 102 is objected to because of the following informalities: the acronym “ARCA” is not defined in the claims. When an acronym is used in a claim set, it should be defined the first time it appears in the claims. For the purposes of examination, the term “ARCA” is interpreted to mean anti-reverse cap analog.
Claim 104 is objected to because of the following informalities: the acronym “PDI” is not defined in the claims. When an acronym is used in a claim set, it should be defined the first time it appears in the claims. For the purposes of examination, the term “PDI” is interpreted to mean polydispersity index.
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 110 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 110 as currently written is vague and indefinite. Claim 110 depends from claim 93. Claim 110 refers to a biodegradable cationic lipid but claim 93 merely refers to a cationic lipid. The recitation biodegradable cationic lipid does not appear until claim 94. Therefore, the claim lacks antecedent basis for the recitation biodegradable cationic lipid.
Claim 110 as currently written is vague and indefinite. While the claim clearly indicates that the amount of the biodegradable cationic lipid is mol%, the claim does not indicate if the amount of the cholesterol, neutral lipid and PEGylated lipid are mol%, wt% or some other unit of measurement.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 93-94, 96-105, 107-108 and 110 are rejected under 35 U.S.C. 103 as being unpatentable over Geall et al. (WO2012030901) in view of Wiederholt et al. (USPGPUB No. 20030083272) as evidenced by Thillier et al. (RNA, February 14 2012).
Applicant Claims
The instant application claims a method of expressing a secreted protein in a mammalian subject, the method comprising administering to the subject a pharmaceutical composition comprising a plurality of lipid nanoparticles encapsulating a polynucleotide, wherein the lipid nanoparticles comprise a cationic lipid, a neutral lipid, cholesterol, and a PEGylated lipid, wherein the plurality of lipid nanoparticles has a mean particle size of from 80 nm to 160 nm, and wherein the polynucleotide comprises:
(a) an open reading frame encoding the secreted protein and consisting of nucleosides selected from uridine, cytidine, adenosine, and guanosine;
(b) a 5’-UTR;
(c) a 5’ cap structure;
(d) a 3’-UTR; and
(e) a 3’ tailing sequence of linked nucleosides.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Geall et al. is directed to small liposomes for delivery of immunogen-encoding RNA. Claimed is a liposome with a diameter in the range of 80-160 nm (claim 2). The liposomes can be formed from a single lipid or a mixture. Where a liposome is formed from a mixture of lipids, it is preferred that the proportion of those lipids which is cationic should be between 20-80% of the total amount of lipids e.g. between 40-60%. The remainder can be cholesterol (e.g. 35-50%) and/or DMA (optionally PEGylated) and/or DSPC (a neutral lipid). It is taught that pegylation can increase stability and prevent non-specific absorption of the liposome. These percentage values are mole percentages. (page 2, lines 22-35). Cationic lipids include 1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane (DLinDMA) (page 2, line 11; lines 27-28). Thus a liposome can be formed from a cationic lipid (e.g. DLinDMA), DSPC, cholesterol and a PEGylated lipid (page 3, lines 7-9; page 21, lines 20-23). Injection intramusucarly is taught. It was shown that expression of the encapsulated RNA increased when the RNA was formulated in the liposome relative to the naked control even at a lower dose (page 23-24, bridging paragraph; Fig. 5).
Geall et al. teaches the RNA may have a 5’ cap (e.g. a 7-methylguanosine). This cap can enhance in vivo translation of the RNA. The RNA may have a 3’-poly-A tail. The RNA may have two open reading frames the first 5’ encodes a replicase and the second 3’ open reading frame encodes an immunogen (page 5, lines 19-22, 28-29, 33-34). The immunogen will be a surface polypeptide (page 8, lines 15-17). The length of the RNA can be from 5000-25000 nucleotides (page 5, lines 24-27). The 5’ nucleotide of a RNA molecule may have a 5’ triphosphate group. In a capped RNA this may be linked to a 7-methylguanosine via a 5’ to 5’ bridge (page 5, lines 30-32). All the RNA nucleosides are standard A, C, G and U ribonucleotides (page 7, lines 30-32). A 3’ URT is taught (page 20 line 28).
Compositions will be administered directly to a patient. Direct delivery may be parenteral injection e.g. intravenous, intramuscular, etc. (page 17, lines 18-20). A typical intramuscular dose is 0.5 ml (page 17, line 24). Dosages can be by a single dose schedule or a multiple dose schedule (page 17 line 28).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Geall et al. teaches an open reading frame, a 3’ UTR, a 5’ cap and a 3’ polyA tail, Geall et al. is silent to a 5’-UTR. However, this deficiency cured by Wiederholt et al.
Wiederholt et al. is directed to sense mRNA therapy. Claimed is a modified, eukaryotic mRNA molecule encoding a therapeutically relevant protein which comprises at least one chemical modification which renders the modified mRNA molecule stable (claim 1). The chemical modification comprises at least one end blocking modification which can be a 5’ blocking modification which can be a modified diguanosine (m7) cap (claims 2, 6-7). The mRNA includes a polyA tail of greater than about 50 bases in length (claim 10) and at least about 90 nucleotides in length (claim 91). It is taught that stabilization of mRNA can be accomplished by increasing length of poly A tail (paragraph 0109). The mRNA can incorporate an optimized Kozak translation initiation sequence (claim 31). Taught is a mRNA with a diguanosine cap: 5’UTR-coding region-3’UTR-polyA tail (paragraph 0143). Reduction in the length of the 5’ and/or 3’UTR can further reduce RNA degradation (paragraph 0060). The mRNA is taught as encoding an immunogen (claim 30).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art at the time of the instant invention to combine the teachings of Geall et al. and Wiederholt et al. and utilize the mRNA of Wiederholt et al. as the mRNA encapsulated by the lipid of Geall et al. One skilled in the art would have been motivated with a reasonable expectation of success to utilize this mRNA as Geall et al. teaches the liposomes are for delivering immune encoding RNA and the mRNA of Wiederholt et al. is taught as encoding an immunogen. Since the mRNA are taught as being stabilized, one skilled in the art would have been motivated to utilize these particular mRNA for their increased stability.
Regarding the claimed polynucleotide structure of claim 92, Geall et al. teaches an open reading frame encoding the protein. The RNA structure includes a 5’-cap, 7-methylguanosine, a 5’-UTR which can be an optimized Kozak translation initiation sequence, a 3’-UTR and a poly-A tail. The immunogen reads on secreted protein.
Regarding claim 94, Geall et al. expressly teaches a cationic lipids which is 1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane (DLinDMA) which is clearly biodegradable. While it may take more time to degrade, it still degrades. Since claim 94 provides no limiting time limit on the time to degrade, DLinDMA reads on claim 94.
Regarding claim 96, Geall et al. teaches the composition comprise an immunologically effective amount of liposomes. This amount varies depending upon the health and physical condition of the individual to be treated, age, the taxonomic group of individual to be treated (e.g. non-human primate, primate, etc.), the capacity of the individual's immune system to synthesize antibodies, the degree of protection desired, the formulation of the vaccine, the treating doctor's assessment of the medical situation, and other relevant factors. It is expected that the amount will fall in a relatively broad range that can be determined through routine trials. The liposome and RNA content of compositions of the invention will generally be expressed in terms of the amount of RNA per dose (page 16, lines 8-19). The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results. This is further supported by Geall et al. which specifically teaches the amount varies depending on a variety of factors. The amount of an active ingredient is a parameter that a person of ordinary skill in the art would routinely optimize based on the condition being treated, severity of the condition and desired dosing frequency, among other factors. It would have been obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). NOTE: MPEP 2144.05.
Regarding claims 97-98, Geall et al. teaches both intramuscular and intravenous administration.
Regarding claim 99, Geall et al. as set forth above, teaches that the dosage can be manipulated depending on a variety of conditions. Geall et al. teaches the same lipid composition. Release is dictated by the lipid composition. Therefore, It would have been obvious to one of ordinary skill in the art at the time of the instant invention to manipulate the lipid composition in order to achieve the desired release rate. Since Geall et al. teaches administering an effective amount, depending on the conditions required, one skilled in the art would manipulate not only the dose but the release rate in order to achieve the optimal effect.
Regarding claim 100-101, Geall et al. and Wiederholt et al. both teach polyA tail. Wiederholt et al. teaches an overlapping range in length of the tail. Wiederholt et al. also teaches that stabilization of mRNA can be accomplished by increasing length of poly A tail. Therefore, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05. Furthermore, one skilled in the art would manipulate the length of the poly A tail in order to achieve the desired level of stabilizing of the mRNA as taught by Wiederholt et al.
Regarding claim 102-103, Geall et al. teaches 7-methylguanosine cap. The 5’ nucleotide of a RNA molecule may have a 5’ triphosphate group. In a capped RNA this may be linked to a 7-methylguanosine via a 5’ to 5’ bridge (page 5, lines 30-32). As evidenced by Thillier et al., the 5’ end carries a N7-methyl guanosine residue linked by a 5’-5’ triphosphate bond. This cap moiety is 7mGpppN which is Cap-O (abstract). Thus, Geall et al. teaches a Cap0.
Regarding claim 104, Geall et al. teaches that the diameters within a population of liposomes should ideally have a polydispersity index <0.2 (page 3, lines 24-26) which overlaps the instant claims. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claim 105, Geall et al. teaches the amount of RNA per liposome can vary. The number per liposome is typically <50 (page 8, lines 4-5). Therefore, one skilled in the art would manipulate the amount in order achieve the desired release and effect as taught by Geall et al.
Regarding claim 107, Wiederholt et al. teaches a codon optimized Kozak sequence.
Regarding claim 108, Geall et al. teaches in Table 1 useful phospholipids which include DSPC.
Regarding claim 110, Geall et al. teaches the proportion of those lipids which is cationic should be between 20-80% of the total amount of lipids e.g. between 40-60%. The remainder can be cholesterol (e.g. 35-50%) and/or DMA (optionally PEGylated) and/or DSPC (a neutral lipid) (page 2). Exemplified amounts of pegylated DMG is 2% and DSPC is 10% (page 33). Therefore, Geall et al. teaches overlapping amounts. Furthermore, it is generally noted that differences in concentration do not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454,456, 105 USPQ 233, 235 (CCPA 1955). Given that applicant did not point out the criticality of the concentration of lipids of the invention, it is concluded that the normal desire of scientists or artisans to improve upon what is already generally known would provide the motivation to determine where in a disclosed set of ranges is the optimum concentration. NOTE: MPEP 2144.05.
Claims 94-95 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Geall et al. in view of Wiederholt et al. as evidenced by Thillier et al. as applied to claims 93-94, 96-105, 107-108 and 110 above and in further view of Chen et al. (WO 2010144740).
Applicant Claims
The instant application claims the cationic lipid is a biodegradable cationic lipid which comprises an ester linkage.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Geall et al. and Wiederholt et al. are set forth above.
Geall et al. teaches cationic lipids.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Geall et al. teaches a cationic lipid such as DLinDMA, Geall et al. does not expressly teach a cationic lipid with an ester linkage. However, this deficiency is cured by Chen et al.
Chen et al. is directed to lipid nanoparticle formulations of polynucleotides and describes a composition wherein the plurality of lipid nanoparticles comprise a cationic lipid, a non-cationic lipid, cholesterol, and a PEG lipid (a lipid particle that consists of or consists essentially of a cationic lipid of formula I, DSPC, Chol and PEG-C-DOMG; page 122, fourth full paragraph; (cationic lipid is DLin-M-C3-DMA; page 5, fourth paragraph), wherein biodegradable cationic lipid comprises an ester linkage (lipid is DLin-M-C3-DMA; page 5, fourth paragraph) which is represented by the formula below clearly showing an ester:
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The plurality of lipid nanoparticles has a mean particle size of between 80 nm and 160 nm (lipid-encapsulated nucleic acid particles, preferably having a diameter of 30 to 150 nm; page 109, first full paragraph).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art at the time of the instant invention to combine the teachings of Geall et al., Wiederholt et al. and Chen et al. and utilize the cationic lipid of formula I, specifically DLin-M-C3-DMA, as the cationic lipid. One skilled in the art would have been motivated replace DLinDMA with Dlin-M-C3-DMA as both are cationic lipids which are used to form lipid formulations with neutral lipids, cholesterol and PEGylated lipid as taught by Chen et al. This substitution amounts to simple substitution of one known element for another to obtain a predictable result. MPEP 2143.
Claim 106 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Geall et al. in view of Wiederholt et al. as evidenced by Thillier et al. as applied to claims 93-94, 96-105, 107-108 and 110 above and in further view of Moretti et al. (RNA, 2010).
Applicant Claims
The instant application claims the 3’-UTR comprises a miR binding site.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Geall et al. and Wiederholt et al. are set forth above. Both teach the RNA comprises a 3’-UTR.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Geall et al. does not teach a miR binding site in the 3’-UTR. However, this deficiency is cured by Moretti et al.
Moretti et al. is directed to mRNA molecules and describes that mRNA molecules contain miR binding sites in the 3' UTR, 5' UTR and open reading frames, and that microRNAs regulate translation of mRNAs by binding to these sites (abstract).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art at the time of the instant invention with a reasonable expectation of success to combine the teachings of Geall et al., Wiederholt et al. and Moretti et al. and utilize miR binding sites in the 3’ UTR as described by Moretti et al. A person of ordinary skill in the art would be motivated to do so in order to regulate the translation of the mRNA as taught by Moretti et al. Since Geall et al. teach an RNA with a 3’-UTR there is a reasonable expectation of success.
Claim 109 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Geall et al. in view of Wiederholt et al. as evidenced by Thillier et al. as applied to claims 93-94, 96-105, 107-108 and 110 above and in further view of Fath et al. ( PLoS ONE; March 2011).
Applicant Claims
The instant application claims the open reading frame is codon optimized to bias GC content.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Geall et al. and Wiederholt et al. are set forth above. Geall et al. teaches an open reading frame.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Geall et al. does not teach the open reding frame is codon optimized to bias GC content. However, this deficiency is cured by Fath et al.
Fath et al. is directed to polynucleotides expressing proteins and describes a polynucleotide wherein the open reading frame is codon optimized (RNA and codon optimization, 50 candidate genes representing five classes of human proteins; abstract) to bias for GC content (optimized the various candidate genes’ coding regions taking the following sequence-based parameters into account: (i) codon choice, (ii) increase in GC-content; page 2, first column, last paragraph). Fath et al. further describe that codon optimization results in reliable and elevated expression (abstract).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art at the time of the instant invention with a reasonable expectation of success to combine the teachings of Geall et al., Wiederholt et al. and Fath et al. codon optimize the sequence of the coding region as described by Fath et al. A person of ordinary skill in the art would have been motivated in order to obtain reliable and elevated expression as taught by Fath et al.
Claim 111 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Geall et al. in view of Wiederholt et al. as evidenced by Thillier et al. as applied to claims 93-94, 96-105, 107-108 and 110 above and in further view of Van Urk et al. (USPGPUB No. 20090171070).
Applicant Claims
The instant application claims the polynucleotide includes at least two stop codons before the 3’-UTR.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Geall et al. and Wiederholt et al. are set forth above.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Geall et al. does not teach at least two stop codons before the 3’-UTRt. However, this deficiency is cured by Van Urk et al.
Van Urk et al. is directed to making proteins in animal cells (recombinant cells may be animal cells (paragraph [0060]), and describes a coding sequence comprising at least two stop codons before the 3’ UTR (cell which comprises a recombinant coding sequence wherein the 3' end of the recombinant coding sequence comprises two or more in-frame translation stop codons; paragraph [0059]). Van Urk et al. further describes that it is beneficial to incorporate more than one stop codon, such as UAA, UAG or UGA, in order to minimize translational read-through and thus avoid the production of elongated, non-natural proteins (paragraph [0101]).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art at the time of the instant invention with a reasonable expectation of success to combine the teachings of Geall et al., Wiederholt et al. and Van Urk et al. and incorporate at least two stop codons. A person of ordinary skill in the art would be motivated to utilize two stop codons in order to minimize translational read-through and thus avoid the production of elongated, non-natural proteins as taught by Van Urk et al.
Examiner’s Comment
The examiner notes that Applicants have previously argued criticality with regard to the size range of the instantly claimed lipid nanoparticles, specifically the remarks filed on July 1 2022 in parent Application 16577734. However, Geall et al. expressly claims a liposome with a diameter in the range of 80-160 nm (claim 2). Which is exactly the same range as instantly claimed. Therefore, criticality of the size of lipid particles in and of itself cannot be utilized to establish an unexpected effect in light of Geall et al.
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.
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Claims 93-111 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11564998 in view of Rosen et al. (USPGPUB No. 20100255574). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims a method of expressing a secreted protein in a mammalian subject, the method comprising administering to the subject a pharmaceutical composition comprising a plurality of lipid nanoparticles encapsulating a polynucleotide, wherein the lipid nanoparticles comprise a cationic lipid, a neutral lipid, cholesterol, and a PEGylated lipid, wherein the plurality of lipid nanoparticles has a mean particle size of from 80 nm to 160 nm, and wherein the polynucleotide comprises:
(a) an open reading frame encoding the secreted protein and consisting of nucleosides selected from uridine, cytidine, adenosine, and guanosine;
(b) a 5’-UTR;
(c) a 5’ cap structure;
(d) a 3’-UTR; and
(e) a 3’ tailing sequence of linked nucleosides
Patent ‘751 claims a method of expressing a polypeptide in a mammalian subject, the method comprising administering to the subject a pharmaceutical composition comprising a plurality of lipid nanoparticles encapsulating a polynucleotide, wherein the lipid nanoparticles comprise a cationic lipid, a neutral lipid, cholesterol, and a PEGylated lipid, wherein the plurality of lipid nanoparticles has a mean particle size of from 80 nm to 160 nm, and
wherein the polynucleotide comprises:
(a) an open reading frame encoding the polypeptide and consisting of nucleosides selected from uridine, cytidine, adenosine, and guanosine;
(b) a 5′-UTR; (c) a 5′ cap structure;
(d) a 3′-UTR; and
(e) a 3′ tailing sequence of linked nucleosides.
The difference between Patent ‘751 and the instant claims is that patent ‘751 claims a polypeptide whereas the instant claims claim a secreted peptide. However, this deficiency is cured by Rosen et al.
Rosen et al. is directed to human secreted proteins. Specifically human secreted polypeptides and isolated nucleic acid molecule encoding said polypeptides useful for diagnosing and treating diseases, disorders and/or conditions related to human secreted proteins (abstract). Taught is a nucleic acid encoding a protein, the nucleic acid can be administered to promote expression of its encoded protein (paragraph 0850).
It would have been obvious to one of ordinary skill in the art at the time of the instant invention with a reasonable expectation of success to combine the teachings of Patent ‘751 and Rosen et al. and utilize a secreted protein (aka secreted peptide) as the polypeptide in Patent ‘751. Patent ‘751 generally claims a polypeptide, Rosen et al. teaches secreted peptides are useful for diagnosing and treating disease and that nucleic acid can be used to promote expression of these proteins. Therefore, it would have been obvious to utilize known peptides in Patent ‘751.
Regarding claims 94-95, Patent ‘751 claims the same in claims 2-3.
Regarding claim 96-98, Patent ‘751 claims the same in claims 4-6.
Regarding claims 99-100, Patent ‘751 claims the same in claims 7-8.
Regarding claims 101-111, Patent ‘751 claims the same in claims 9-19.
Conclusion
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/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636