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 .
Response to Amendment
The Applicant’s remarks filed 07/24/2026 is acknowledged.
Claims 1, 23, 24, 162, 163, and 165-174 are pending and under examination.
Claim Rejections - 35 USC § 103 - Maintained
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.
Claim(s) 1, 23, 24, 162, 163, 165-170, and 172 is/are rejected under 35 U.S.C. 103 as being unpatentable over Heartlein (WO2013185067A1, published December 12th, 2013), further in view of Qiagen (www.qiagen.com/us/resources/download.aspx?id=410c163c-16b6-42ae-9e61-9053c6d77ad2&lang=en; published 2017).
Regarding claims 1, 162, 163, and 165, Heartlein discloses a composition comprising:
(a) an mRNA (i.e., polynucleotide) encoding a polypeptide comprising:
(i) a 5'-cap structure;
(ii) a 5'-untranslated region (5'-UTR);
(iii) an open reading frame encoding the polypeptide;
(iv) a 3'-untranslated region (3'-UTR); and
(v) a poly-A region; and
(b) three or more oligonucleotides that are hybridized to the mRNA, wherein each oligonucleotide comprises a region of linked nucleotides complementary to a different portion of the nucleic acid sequence of the mRNA (Fig. 1) [0013, 0023, 0037, 0039].
Heartlein does not explicitly disclose the three or more oligonucleotides (or at least three and no more than ten oligonucleotides – claim 162) (or at least ten and no more than fifty oligonucleotides – claim 163) being simultaneously hybridized to the mRNA. However, [0032] of Heartlein discloses:
“As used herein, the terms "contact" and "contacting" generally refer to bringing two or more moieties together or within close proximity of one another such that the moieties may react. For example, in certain embodiments of the present invention, a polynucleotide (e.g., an mRNA transcript) may be contacted with one or more stabilizing oligonucleotides (e.g., a stabilizing oligonucleotide that is perfectly complementary to a region or fragment of the polynucleotide) such that the polynucleotide and stabilizing oligonucleotide would be expected to react (e.g., hybridize to one another) under suitable conditions.”
As written, although [0032] states the singular “stabilizing nucleotide” in the second-to-last line in reference to hybridization, one of ordinary skill may still interpret this teaching to also apply to the “one or more stabilizing oligonucleotides” referred to in the same sentence that may contact a polynucleotide/mRNA transcript. In addition, the term “moieties” (e.g., as recited in [0032], “two or more moieties”) is interpreted to read on oligonucleotides. In the example describing the “contacting” of two or more moieties in [0032], Heartlein describes a polynucleotide being contacted with one or more stabilizing oligonucleotides. As such, a stabilizing oligonucleotide is considered a moiety in view of [0032] of Heartlein, and the recitation of “two or more” means at least three.
Additionally, Figure 1 of Heartlein illustrates at least two oligonucleotides binding simultaneously to the same mRNA target. Further, there is nothing to suggest that the recitation of “multiple oligo binding” and “one or more” restricts the teachings of Heartlein to only two oligonucleotides binding, and would not read on at least three and no more than ten oligonucleotides (claim 162), or at least ten and no more than fifty oligonucleotides (claim 163). The combined teachings of [0032] and Figure 1 of Heartlein provide evidence that the ordinary artisan previously recognized the scientific and technical concept that multiple oligonucleotides can bind simultaneously to the same mRNA target, per natural law of chemistry and cell biology. Further, the teachings of Heartlein (e.g., “multiple oligo binding”, “two or more moieties”, “one or more stabilizing oligonucleotides”, etc.) overlap with the number of oligonucleotides recited in the instant specification.
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). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
Additionally, the instant specification fails to disclose an element of criticality for the number of oligonucleotides (e.g., three or more) that are simultaneously hybridized to the mRNA.
There is no clear evidence that the oligonucleotides/number of oligonucleotides (e.g., “multiple oligo binding”, “two or more moieties”, “one or more stabilizing oligonucleotides”, etc.) of the current invention would function different from the oligonucleotides/number of oligonucleotides taught by Heartlein, nor that the number of oligonucleotides is critical (i.e., produces unexpected results) compared to the range taught by Heartlein.
Heartlein also does not explicitly disclose “the three or more oligonucleotides collectively comprise regions of linked nucleotides complementary to 10% or more of the sequence of the mRNA”.
The instant specification discloses that each oligonucleotide may comprise as many as 100 nucleotides or 50 nucleotides (e.g., pg. 2, lines 5-8), and additionally, each oligonucleotide includes a region of linked nucleotides complementary to a portion of a sequence of the mRNA, wherein the region of linked nucleotides may be at least 50 nucleotides (e.g., pg. 2, lines 9-11).
Heartlein teaches that stabilizing oligonucleotides “may generally be of any length”, including less than 500 nucleotides, but preferably less than 75 or less than 50 nucleotides [0034, 0036]. Heartlein teaches that the stabilizing oligonucleotides may be 100% complementary to the target mRNA [0010]. As such, for example, three oligonucleotides taught by Heartlein may be 75 nucleotides in length and 100% complementary, resulting in 225 nucleotides being complementary to the mRNA.
Further, Heartlein teaches targeting the poly-A tail with stabilizing oligonucleotides (e.g., 15-mers), wherein the poly-A tail sequence may be at least 20 nucleotides in length [0053]. Even if the poly-A sequence is at least 500 nucleotides in length (the largest recited by Heartlein in [0053]), three of the example 15-mer oligonucleotides would collectively be 11% complementary to the mRNA.
Considering the length of the oligonucleotides taught by Heartlein (e.g., 500 nts, 75 nts, etc.) that can be 100% complementary to a target mRNA (i.e., 500, 75, etc. nucleotides would be complementary) and the examples provided, before the effective filing date of the instant case, one of ordinary skill in the art would have reasonably understood that the teachings of Heartlein reasonably infer the limitation of the three or more oligonucleotides collectively being complementary to 10% or more (or 50% - claim 165) of the sequence of the mRNA. Additionally, the size of the stabilizing oligonucleotides of Heartlein overlap with the size of the oligonucleotides recited in the instant specification.
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). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
Additionally, the instant specification fails to disclose an element of criticality for the oligonucleotides collectively comprising regions of linked nucleotides complementary to 10% (or 50%) or more of the sequence of the mRNA.
There is no clear evidence that the oligonucleotides of the current invention would function different from the oligonucleotides taught by Heartlein, nor that the length of oligonucleotides/mRNA/collective percentage complementary is critical (i.e., produces unexpected results) compared to the range taught by Heartlein.
Further, Qiagen teaches that the average length of mRNA in humans is ~1900 nucleotides (Table 1, line 1 under “RNA sizes and molecular weights – Prokaryotic vs. Eukaryotic”). The teachings of Qiagen exemplify what the ordinary artisan previously understood the average mRNA length to be. One therefore would have reasonably understood the teachings of Heartlein to reasonably infer the limitation of the three or more oligonucleotides collectively being complementary to 10% or more (or 50% - claim 165) of the sequence of the mRNA. For example, if three oligonucleotides of Heartlein were 500 nucleotides in length and were 100% complementary [0010, 0034] (e.g., 1500 complementary nucleotides) to a target mRNA that is the average length of mRNA in humans (e.g., 1900 nucleotides in length as taught by Qiagen), this would result in the oligonucleotides collectively being 79% complementary to the mRNA.
Regarding claim 23, Heartlein teaches the composition being associated with a lipid nanoparticle [0012].
Regarding claim 24, Heartlein teaches a pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically-acceptable excipient [0012].
Regarding claim 166, Heartlein teaches the three or more oligonucleotides each comprising between 6 and 100 nucleotides (i.e., less than 100 nucleotides, more preferably less than 50 nucleotides…) ([0034], claims 51 and 52).
Regarding claim 167, Heartlein teaches the three or more oligonucleotides comprising a region of linked nucleotides complementary to a portion of a sequence of the mRNA, wherein the region of linked nucleotides is at least 5 nucleotides (i.e., at least 10 nucleotides in length) (claims 44, 45, and 47).
Regarding claims 168 and 169, Heartlein teaches the three or more oligonucleotides comprising at least one 2'-OMe nucleotide (claim 169), 2'-MOE nucleotide, 2'- F nucleotide, 2'-NH2 nucleotide, FANA nucleotide, LNA nucleotide, 4'-S nucleotide, TNA nucleotide, or PNA nucleotide ([0016], includes 2'-OMe, 2'-F, LNA, PNA, and 2'-MOE).
Regarding claim 170, Heartlein teaches at least one of the three or more oligonucleotides comprising a region of linked nucleotides complementary to a portion of the sequence of the 5'-UTR or the 3'-UTR [0010].
Regarding claim 172, Heartlein teaches at least one of the three or more oligonucleotides is conjugated to a moiety selected from a sterol, a polyethylene glycol, a polylactic acid, a sugar, a toll-like receptor antagonist, or an endosomal escape peptide (i.e., 2’-O-alkyl sugar modification) (pg. 7, [0015]).
Claim(s) 171 is/are rejected under 35 U.S.C. 103 as being unpatentable over Heartlein and Qiagen, as applied to claims 1, 23, 24, 162, 163, 165-170, and 172 above, further in view of Roy (US20170136132A1, published 5/18/2017).
Heartlein and Qiagen do not explicitly teach at least one of the three or more oligonucleotides comprises a region of linked nucleotides complementary to a portion of the sequence of the start codon.
Heartlein teaches at least one of the oligonucleotides comprising a region of linked nucleotides complementary to a portion of the sequence of the 3' untranslated region (UTR), the 5' untranslated region (UTR), the poly-A tail and a terminal cap [0010].
Heartlein teaches “While certain embodiments described herein contemplate the hybridization of the stabilizing oligonucleotide to the non-coding region of the polynucleotide, the present inventions are not limited to such embodiments. Rather, also contemplated are methods and compositions in which the stabilizing oligonucleotide hybridizes to a region spanning or comprising both a fragment of the coding region as well as a fragment of the non-coding region of the polynucleotide” [0011]. Additionally, Heartlein teaches that “the phrase "coding region" generally refers to that portion or region of the polynucleotide or a gene that when expressed, transcribed, translated or otherwise processed results in the production of an expression product, such as an amino acid, polypeptide, protein or enzyme” [0041].
Roy teaches compositions and methods using alternative nucleic acids to modulate cellular function [0002]. Specifically, Roy teaches an mRNA encoding a polypeptide of interest, the mRNA including at least one 5′ cap structure; a 5′-UTR, e.g., a 5′-UTR including a Kozak sequence; a 3′-UTR, and a poly-A tail [0010, 0019]. The mRNA may be stabilized by the addition of an oligonucleotide [1910, 1914]. Roy also teaches the use of antisense LNA oligonucleotides to stabilize mRNA (i.e., an oligonucleotides complementary to a portion of the start codon) [2017, 2033]. The examiner notes that “miRNAs” are considered a type of oligonucleotide, and that Roy also teaches miRNAs being used to stabilize mRNA [1970]
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute at least one of the oligonucleotides comprising a region of linked nucleotides complementary to a portion of a sequence (e.g., 5’-UTR, 3’-UTR), as taught by Heartlein, with an oligonucleotide comprising a region of linked nucleotides complementary to a portion of the sequence of the start codon, as taught by Roy with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Further, Heartlein contemplates embodiments of oligonucleotides complementary to coding and non-coding regions of mRNA [0011].
M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06.
An artisan would be motivated to substitute at least one oligonucleotide taught by Heartlein with an oligonucleotide comprising a region of linked nucleotides complementary to a portion of the sequence of the start codon because Roy taught that such oligonucleotide(s) would decrease accessibility of the site of translation initiation/first start codon [2017, 2033].
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
Claim(s) 173 and 174 is/are rejected under 35 U.S.C. 103 as being unpatentable over Heartlein and Qiagen, as applied to claims 1, 23, 24, 162, 163, 165-170, and 172 above, further in view of Ozsolak (US20150050738A1, published 2/19/2015).
Heartlein and Qiagen do not explicitly teach at least one of the three or more oligonucleotides being conjugated to a moiety, the moiety being cholesterol.
Heartlein teaches the oligonucleotides being conjugated to a moiety such as sugar (i.e., a sugar modification) [0015].
Ozsolak teaches compositions comprising an mRNA encoding a polypeptide comprising a 5’ cap structure, a 5’ UTR, an open reading frame encoding the polypeptide, a 3’-UTR, and a poly-A region, and one or more oligonucleotides that are hybridized to the mRNA (e.g., claim 46 of Ozsolak) [0013, 0015, 0023, 0028, 0215, 0139]. Additionally, Ozsolak teaches that the oligonucleotide(s) may be conjugated a label or targeting moiety, such as cholesterol [0159].
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a moiety (e.g., sugar) (that is conjugated to an oligonucleotide), taught by Heartlein, with cholesterol (which is also conjugated to an oligonucleotide), as taught by Ozsolak with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Although Heartlein does not specifically state that the oligonucleotides are conjugated to cholesterol, Heartlein does contemplate carriers/lipid nanoparticles encapsulating mRNA and/or oligonucleotides, and moieties/lipids such as cholesterol in order to facilitate delivery of the nuclease resistant polynucleotides or stabilizing oligonucleotides to one or more target cells, organs or tissues, and teaches that targeting ligands, such as oligonucleotides, can be conjugated to moieties present in the carrier [0064-0067, 0071, 0090].
M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06.
An artisan would be motivated to substitute at least one moiety taught by Heartlein with cholesterol because as taught by Ozsolak, chemically linking oligonucleotides (i.e., conjugating) with moieties such as cholesterol enhance the activity, cellular distribution, or cellular uptake of the oligonucleotide [0191, 0192].
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
Response to Arguments
Applicant's arguments filed 07/24/2026 are considered below.
Regarding Heartlein, the Applicant argues:
“When discussing Heartlein, the Office relies heavily upon paragraph [0032] as allegedly disclosing or suggesting the "three or more oligonucleotides" limitations. On its face, it is clear to one of skill in the art that this paragraph is discussing bringing moieties together such that they react. As an example, Heartlein discusses contacting an mRNA with a stabilizing oligonucleotide. The Office takes this simple paragraph and interprets it as disclosing "at least three" stabilizing oligonucleotides. Applicant respectfully submits the Office's logic is flawed.
Applicant does not disagree that the "one or more oligonucleotides" of Heartlein would be considered a "moiety" as defined in Heartlein. But the Office seemingly suggests that the "two or more moieties" means "two or more oligonucleotides." This ignores the fact that the polynucleotide (e.g., mRNA) is one of the moieties, and it has to be contacted by another moiety - i.e., the one or more stabilizing oligonucleotides. Thus, Heartlein does not disclose anything more than "one or more" oligonucleotides hybridized to an mRNA. The Office also states that "two or more means at least three," which Applicant submits is self-evidently not true.” (pg. 1).
These arguments are considered but not found to be persuasive. Heartlein teaches one or more stabilizing oligonucleotides contacting mRNA (e.g., [0032]). Although Heartlein doesn’t exactly recite “three or more”, why would “one or more stabilizing oligonucleotides” and “multiple oligos” as recited in Heartlein not encompass/read on the claim language of “three or more oligonucleotides”? The Applicant fails to provide evidence or distinctly point out why an artisan would not interpret “one or more stabilizing oligonucleotides” and “multiple oligos” to encompass “three or more” (e.g., why would one conclude that “one or more” and/or “multiple” does not mean three oligos may be present?).
The Applicant further argues:
“Heartlein does not disclose a range that overlaps with the claimed three or more oligonucleotides
As discussed above, Heartlein does not disclose anything more than "one or more stabilizing oligonucleotides." The Office relies on the portions of the M.P.E.P., and the cases cited therein, relating to overlapping or close ranges and suggests that the disclosure of "one or more stabilizing oligonucleotides" and "multiple oligo binding" overlap with the claimed ranges. However, Applicant submits that these terms do not disclose a range at all and instead merely represent an unbounded disclosure of any possible number of oligonucleotides. "One or more" and "multiple" simply refer to any possible number. Thus, Applicant submits the cases relating to overlapping ranges are inapplicable.”
This argument is considered but not found to be persuasive. The Examiner agrees that Heartlein and the instant claims do not recite a definite range of values, however the case law is still viewed as applicable. While the recitations of Heartlein may be broader in scope than the instant claims, they still encompass the entirety of the “three or more” limitation recited in claim 1. Depending on one’s intentions, an artisan may reasonably conclude to use (for example) three oligonucleotides based on the teachings of Heartlein. Additionally, if “one or more” and “multiple” are viewed to “merely represent an unbounded disclosure of any possible number of oligonucleotides” and “simply refer to any possible number”, would the same not be said for “three or more” as recited in the instant claims?
The Applicant also argues:
“Heartlein fails to provide a motivation to pursue a composition comprising three or more oligonucleotides simultaneously hybridized to an mRNA molecule. The Office looks to portions of Heartlein and Qiagen as allegedly teaching multiple oligonucleotides hybridized to at least 10% (or at least 50%) of the mRNA. In doing so, the Office seemingly creates hypothetical embodiments by selecting particular pieces of Heartlein's disclosure to recreate what is contained in Applicant's claim. For example, the Office assumes three 500mer oligonucleotides that are 100% complementary to an mRNA molecule. But Heartlein never actually discloses such an embodiment, and there is no suggestion that one would be effective. Thus, there is no motivation to arrive at the claimed subject matter based on Heartlein in view of Qiagen. Applicant therefore submits the Office has not established a prima facie case of obviousness and any discussion of "no criticality" by the Office is premature.”
These argument(s) has been fully considered, but is not persuasive. Applicant argues that Heartlein does not disclose a reduction to practice or exact embodiment of the instantly claimed composition. Rather, the Examiner is picking and choosing various parts of the Heartlein disclosure.
The specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970).
A reference contains an "enabling disclosure" if the public was in possession of the claimed invention before the date of invention. "Such possession is effected if one of ordinary skill in the art could have combined the publication's description of the invention with his [or her] own knowledge to make the claimed invention." In re Donohue, 766 F.2d 531, 226 USPQ 619 (Fed. Cir. 1985).
Applicant fails to provide objective evidence that a composition comprising three or more oligonucleotides that are simultaneously hybridized to mRNA constitutes undue experimentation, for example.
Additionally, Heartlein teaches that the oligonucleotides may be 100% complementary to the mRNA (e.g., [0010]), as well as less than 15 to less than 500 nucleotides in length (preferably 1-50 nucleotides or about 15 nucleotides, e.g., claims 8 and 9 or Heartlein). Heartlein provides poly-A tail as an example mRNA for the oligonucleotide(s) to hybridize to, which may be anywhere from at least 20 nucleotides to 500 nucleotides in length. Based on the teachings of Heartlein and Qiagen, an artisan would reasonably conclude that multiple oligonucleotides may hybridize to at least 10% (or at least 50%) of the mRNA. Further, the Applicant fails to distinctly point out or provide evidence as to the criticality of at least 10% (or 50%) (e.g., would this percentage produce unexpected results? Is hybridizing to at least 10% (or at least 50%) of the mRNA novel/constitute undue experimentation? Why would the oligonucleotides of Heartlein be unable to hybridize to at least 10% of the mRNA, depending on the discretion/intentions of an artisan?).
Citation of Relevant Prior Art
UMass (US20060293267A1) is considered relevant prior art for teaching synthesizing a series of 2′-O-methyl oligonucleotides with complementarity to different portions of a target luciferase mRNA sequence (e.g. 5′-UTR, ORF, 3′UTR) to determine which portion of the target sequence is most effectively targeted (e.g., [0228]; Fig. 1B).
Aceragen Inc. (US20100035967A1) is considered relevant prior art for teaching the modulation of TLR9 expression with antisense oligonucleotides. Aceragen Inc. teaches multiple oligonucleotides are specifically contacted or hybridized with TLR9 mRNA either in vitro or in a cell (e.g., [0019]). Aceragen Inc notes it may be desirable to administer simultaneously, or sequentially a therapeutically effective amount of one or more (or two or more) of the therapeutic TLR9 antisense oligonucleotides of the invention to an individual as a single treatment episode.” (e.g., [0093], [0105]).
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ALLISON MARIE JOHNSON/Examiner, Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638
