DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
Election/Restrictions
Applicant's election without traverse of Group II, claims 51, 54-55, 57, and 62, and newly added claims 63-76 in the reply filed on 04/24/2026 is acknowledged.
During a telephone conversation with Lisa Hillman on 05/13/2026 a provisional election was made without traverse to prosecute the species of mRNA as the active agent, DSPC as the phospholipid, Dlin-MC3-DMA (MC3) as the cationic lipid, and DMG-PEG2000 as the PEGylated lipid. Affirmation of this election must be made by applicant in replying to this Office action.
Claims 1-2, 4-8, 12, 20, 30, 34, 37, 40, 49, and 53 drawn to the non-elected invention have been cancelled by the applicant.
Claim 75 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 51, 54-55, 57, 62-74, and 76 read on the elected invention and species and are currently under examination.
Claim Objections
Claim 73 is to because of the following informality:
In claim 73 the drawn phospholipid formula should be labeled as (IV). Appropriate correction is required.
Claim Rejections - 35 USC § 112, Second Paragraph
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 54 and 72 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 54 recites the limitation “the polypeptide of interest" in line 2. There is insufficient antecedent basis for the limitation “the polypeptide” in the claim. To overcome this rejection, the limitation can be changed to “a polypeptide”.
Regarding claim 72, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 72 recites the broad recitation “the cationic lipid is of Formula I”, and the claim also recites “preferably the cationic lipid of formula I is…” (claims pg. 5, two lines before Formula II is drawn) which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. To overcome this rejection, “preferably” language can be removed from the claim.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 51, 54-55, 57, and 62-74, and 76 are rejected under 35 U.S.C. 102 as being as being anticipated by Besin et al. (US 2019/0117798 A1).
Claim 51 is anticipated because Besin discloses a lipid nanoparticle with mRNA cargo and MC3:DSPC:Chol:PEG-DMG in a mol % of 50:11.25:38.5:0.25 ([0976]-[0977], Table 3, 2nd Example). Besin discloses that the lipid nanoparticles are contacted with a cell, thereby introducing the active agent to the cell [0977].
Regarding the molar percentages of the lipid component, If the prior art discloses a point within the claimed range, the prior art anticipates the claim. See MPEP 2131.03.
Claim 54 is anticipated because the active agent is mRNA ([0976]-[0977]), which is translated in the cell and produces the protein of interest [0818].
Claim 55 is anticipated because the active agent is mRNA which is delivered into a cell ([0976]-[0977]).
Claims 57 and 62 are anticipated because Besin teaches that the lipid nanoparticles are delivered to a subject [0024] and when the LNP is administered to a subject the LNP is rapidly transported through the blood to the spleen [0312].
Claims 63-64 are anticipated because while Besin does not explicitly teach that the lipid nanoparticle preferably targets the spleen in comparison to the liver with the claimed targeting ratio, a chemical composition and its properties are inseparable. MPEP 2112.01 II. Therefore, because the prior art teaches a lipid nanoparticle with the same components, the properties the applicant discloses and/or claims (i.e., preferentially targeting spleen with claimed targeting ratio) are reasonably expected to be necessarily present, especially as Besin teaches that when the LNP is administered to a subject the LNP is rapidly transported through the blood to the spleen [0312].
Claims 65-66 are anticipated because the PEGylated lipid (PEG-DMG) is present in an amount of 0.25 mol % of the total lipid present in the particle ([0976]-[0977], Table 3, 2nd Example). If the prior art discloses a point within the claimed range, the prior art anticipates the claim. See MPEP 2131.03.
Claim 67 is anticipated because in the 2nd Example of Table 3 the PEGylated lipid (PEG-DMG) is present in an amount of 0.25 mol % of the total lipid present in the particle and in the 3rd Example PEG-DMG is present in an amount of 0.50 mol % ([0976]-[0977], Table 3). The claimed subject matter is disclosed in the reference with sufficient specificity to constitute an anticipation rejection. See MPEP 2131.03 II.
Claims 68-71 are anticipated because the PEGylated lipid is PEG-DMG ([0976]-[0977], Table 3, 2nd Example). The structure is shown at [0645] indicating that the PEG-DMG is DMG-PEG2000.
Claim 72 is anticipated because the cationic lipid is MC3 ([0976]-[0977], Table 3, 2nd Example).
Claim 73 is anticipated because the phospholipid is DSPC ([0976]-[0977], Table 3, 2nd Example).
Claim 74 is anticipated because the structural lipid is cholesterol ([0976]-[0977], Table 3, 2nd Example).
Claim 76 is anticipated because the active agent is mRNA ([0976]-[0977], Table 3, 2nd Example).
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 57, 62-64, 67-71 are rejected under 35 U.S.C. 103 as being as being obvious over Besin et al. (US 2019/0117798 A1).
Besin is believed to anticipate claim 62 as described above, but in the interest of completeness of prosecution, purely arguendo, and for the purposes of this ground of rejection only, Besin will be interpreted as if it is not anticipatory over claim 62.
In that case, Besin could be construed as not clearly and unequivocally disclosing the claimed invention or directing those skilled in the art to the claimed invention without any need for picking, choosing and combining various disclosures not directly related to each other by the teachings of the cited reference. Namely, one skilled in the art would need to choose to deliver the lipid nanoparticle taught at [0976]-[0977] to a subject ([0024] [0312]).
Nevertheless, it is prima facie obvious to combine prior art elements according to known methods, to yield predictable results. In the instant case, all the claimed elements (e.g., lipid nanoparticle; delivering lipid nanoparticles to a subject) were known in the prior art (e.g., Besin) and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielding nothing more than predictable results to one of ordinary skill in the art. MPEP 2143.A.
Furthermore, Besin teaches that delivering a lipid nanoparticle encapsulating a therapeutic agent, such as mRNA, to a subject is beneficial to treat a disease/condition [0091] [0369] [0820]. An ordinarily skilled artisan would be motivated to deliver the lipid nanoparticle with mRNA taught at [0976]-[0977] to a subject in order to treat a disease or condition [0091] [0369] [0820].
Claim 57 is rendered prima facie obvious because Besin teaches that when the LNP is administered to a subject the LNP is rapidly transported through the blood to the spleen [0312].
Claims 63-64 are rendered prima facie obvious because while Besin does not explicitly teach that the lipid nanoparticle preferentially targets the spleen in comparison to the liver with the claimed targeting ratio, a chemical composition and its properties are inseparable. MPEP 2112.01 II. Therefore, because the prior art teaches a lipid nanoparticle with the same components, the properties the applicant discloses and/or claims (i.e., preferentially targeting the spleen with claimed targeting ratio) are reasonably expected to be necessarily present, especially as Besin teaches that when the LNP is administered to a subject the LNP is rapidly transported through the blood to the spleen [0312].
Claim 67 is believed to be anticipated as discussed above, but in the alternative, claim 67 is rendered prima facie obvious because in the 2nd Example of Table 3 the PEGylated lipid (PEG-DMG) is present in an amount of 0.25 mol % of the total lipid present in the particle and in the 3rd Example PEG-DMG is present in an amount of 0.50 mol % ([0976]-[0977], Table 3). In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05 A.
Claims 68-71 are considered anticipated as discussed above because the PEGylated lipid is disclosed to be PEG-DMG ([0976]-[0977], Table 3, 2nd Example) which is believed to be DMG-PEG2000 [0645]. In the alternative, it would have been prima facie obvious to use DMG-PEG2000 because compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. See MPEP 2144.09.
Claims 51, 54-55, 57, 62-74, and 76 are rejected under 35 U.S.C. 103 as being as being obvious over Valadi et al. (WO 2020/002540 A1).
Regarding claim 51, Valadi discloses a method of delivering mRNA to a cell by contacting the cell with a lipid nanoparticle comprising mRNA under conditions that allow lipid nanoparticle uptake by the cell [25] [31]. A specific embodiment is taught at [201]-[202] with mRNA and a lipid nanoparticle with MC3 in an amount of 50 mol %, DSPC in an amount of 10 mol %, cholesterol in an amount of 38.5 mol %, and PEG2000-DMPE in an amount of 1.5 mol %. PEG2000-DMPE is discloses as a PEG lipid which Valadi teaches may be present in the lipid nanoparticle in an amount of about 0 to about 20 mol % [128]. Valadi also discloses PEG2000- DMG as a PEG lipid to be used in the lipid nanoparticle [127].
Valadi is not believed to be anticipatory because the instant claim 51 recites that the PEGylated lipid is present in an amount of “about 0.05 mol % to about 0.5 mol %” whereas the specific embodiment taught by Valadi discloses the PEGylated lipid in an amount of 1.5 mol %.
However, Valadi teaches that the PEG lipid may be present in the lipid nanoparticle in an amount of about 0 to about 20 mol % [128], in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. See MPEP 2144.05 A. Furthermore, 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. See MPEP 2144.05(II)(A). In this case, the general condition of the amount of PEG lipid has been taught by Valadi; as such, it would not have been inventive for the skilled artisan to have discovered the optimum amount within the teachings of Valadi via routine experimentation.
Further regarding claim 51, while the embodiment taught at [201]-[202] does not include the elected PEG lipid, PEG2000- DMG, Valadi discloses both PEG2000- DMG and PEG2000-DMPE as PEG lipids [127]. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. In the instant case, since Valadi taught both PEG2000- DMG and PEG2000-DMPE as PEG lipids to be used in the lipid nanoparticle, it is prima facie obvious to select PEG2000- DMG for incorporation into the lipid nanoparticle based on its recognized suitability for the intended use as a PEG lipid, as taught by Valadi.
Claim 54 is rendered prima facie obvious because Valadi discloses that the active agent is mRNA [201]-[202] and that the mRNA is functional and can be translated to produce a therapeutic protein [204].
Claim 55 is rendered prima facie obvious because Valadi discloses that the active agent is mRNA [201]-[202].
Claims 57 and 62 are rendered prima facie obvious because Valadi discloses the cell is present in a subject [claim 56] and the active agent is delivered to the spleen of a subject [223]-[224].
Claims 63-64 are rendered prima facie obvious because Valadi discloses the active agent is delivered to the spleen of a subject [223]-[224] and the spleen is the organ with the highest amount of hEPO mRNA (FIG. 4G) [224]. The amount of hEPO mRNA present in the spleen is about 190 ng/g of organ after 5 hours (Fig 4G) whereas the amount of hEPO mRNA present in the liver is about 7 ng/g of organ (Fig 4E), indicating a targeting ratio of at least greater than 2.
Claims 65-67 are rendered prima facie obvious because Valadi discloses the PEG lipid is present in the lipid nanoparticle in an amount of about 0 to about 20 mol % [128]. A prima facie case of obviousness exists because of overlap, as previously discussed.
Claims 68-71 are rendered prima facie obvious because Valadi discloses PEG2000- DMG as a PEG lipid to be used in the lipid nanoparticle [127].
Claim 72 is rendered prima facie obvious because Valadi discloses the cationic lipid, MC3 [201]-[202].
Claim 73 is rendered prima facie obvious because Valadi discloses the phospholipid, DSPC [201]-[202].
Claim 74 is rendered prima facie obvious because Valadi discloses the structural lipid, cholesterol [201]-[202].
Claim 76 is rendered prima facie obvious because Valadi discloses that the active agent is mRNA [09] [201]-[202].
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ashlee E Wertz whose telephone number is (571)270-7663. The examiner can normally be reached Monday - Friday, 8 AM - 5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at 571-272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ASHLEE E WERTZ/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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