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 .
Status of the Claims
Claims 23, 27, and 32-42 are pending in this application. Claims 1-22, 24-26, and 28-31 have been cancelled by applicant. Claims 23, 27, 32, and 34-42 are under examination herein. Claim 33 is withdrawn from consideration.
Claim Interpretation
Claim 23 speaks to a composition comprising “an agent”. The specification defines “therapeutic agents” as any composition that has a beneficial biological effect (page 18). The specification also mentions, in certain embodiments, the agent is a small molecule, organometallic compound, nucleic acid, peptide, polynucleotide, RNA, mRNA metal, targeting agent, drug, vaccine, etc. (page 41, line 30).
Therefore, the term “agent” in the claims will be broadly interpreted to encompass any drug or small molecule therapeutics, as well as polynucleotides, RNA, peptides, etc. (In re Hyatt, 211 F.3d1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000) (see MPEP 2111).
Claim 27 speaks to a non-cationic liquid. The specification indicates, in some embodiments, non-cationic liquids can include: 1,2-dioleoyl-sn-glycero- 3-phosphoethanolamine (DOPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1-stearoyl-2-oleoyl-sn-glycero- 3-phosphoethanolamine (SOPE), DPPC (1,2-dipalmitoyl-sn-glycero-3- phosphocholine), 1,2- dioleyl-sn-glycero-3-phosphotidylcholine (DOPC), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE), 1,2-dioleoyl-5/7-glycero-3- phospho-(l'-rac-glycerol) (DOPG), or combinations thereof. In one embodiment, the non-cationic lipid is 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) (page 38, line 28).
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 35 and 40-42 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 35 recites the limitation "the nanoparticle" in line 1. There is insufficient antecedent basis for this limitation in the claim, which depends from claim 23, which refers to a composition, not a nanoparticle. It is believed Applicant intended for claim 35 to depend upon claim 27. For the purposes of applying art, claim 35 will be interpreted as being dependent upon claim 27.
Claim 40 is indefinite because it is presented as being dependent upon itself. For the purposes of applying art, claim 40 will be interpreted as being dependent upon claim 27.
Claims 41-42 are rejected for depending upon the limitations of indefinite claim 40.
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.
Claims 23, 27, 32, and 34-42 are rejected under 35 U.S.C. 103 as being unpatentable over Le Corre et al. (Eur. J. Org. Chem. 2014, 8041–8048 – cited in IDS – previously cited) (“Le Corre”); in view of Guild et al. (US 10,507,249 B2 – previously cited) (“Guild”).
Regarding claims 23, 27, and 34-35, Le Corre discloses compound 7 below, which is the same as the instantly elected species (Scheme 1(B), page 8043). Le Corre discloses how their liposome formulations were prepared with the cationic lipid derived from the elected compound in the instant invention (page 8047, col. 2, para. 2).
PNG
media_image1.png
141
262
media_image1.png
Greyscale
, wherein the Olelyl group is defined as:
PNG
media_image2.png
48
630
media_image2.png
Greyscale
While Le Corre does not specifically teach: (i) a composition for delivering an agent into a cell comprising the elected alkyl phosphate lipid and an agent (claim 23); (ii) a nanoparticle comprising the elected alkyl phosphate lipid, a non-cationic lipid, a PEG lipid, and a sterol (claim 27); (iii) a pharmaceutical composition comprising the elected alkyl phosphate lipid and an acceptable carrier (claim 32); or (iv) wherein the agent is a polynucleotide, an RNA, or mRNA (claims 34-42); the teachings of Guild are relied upon for these disclosures.
Guild discloses lipid nanoparticle compositions and methods of mRNA delivery (title and abstract). Guild teaches one reason that mRNA based gene therapy has not been used more in the past is that mRNA is far less stable than DNA, especially when it reaches the cytoplasm of a cell and is exposed to degrading enzymes; certain delivery vehicles, such as cationic lipid may also help protect the transfected mRNA (col. 2, last para.); Guild specifically discloses compositions and methods for intracellular delivery of mRNA in a liposomal transfer vehicle (col. 3, lines 24-26). Guild discloses their mRNA is formulated in a liposomal transfer vehicle may comprise one or more non-cationic lipids, PEG-modified lipids, and may further comprise cholesterol (reading on a sterol – claim 27) (col. 4, lines 15-17). Guild discloses their compositions comprise a transfer vehicle, such as pharmaceutically acceptable carriers, diluents, excipients, etc. (reading on claims 23, 27, and 32) (col. 9, lines 5-10). Guild further discloses the properties of the transfer vehicle (e.g., size, charge and/or pH) may be optimized to effectively deliver transfer vehicle to the target cell, reduce immune clearance and/or promote retention in that target cell (col. 14, lines 13-16). Guild teaches liposomes (e.g., liposomal lipid nanoparticles) are generally useful in a variety of applications in research, industry, and medicine, particularly for their use as transfer vehicles of diagnostic or therapeutic compounds in vivo (col. 14, lines 31-35), and that liposomes are typically formed by amphiphilic molecules, such as lipids of synthetic or natural origin that comprise spatially separated hydrophilic and hydrophobic domains (col. 14, lines 40-43).
Therefore, regarding instant claims 23, 27, and 34-35, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to prepare a composition comprising the instant compounds and mRNA; or a nanoparticle comprising the instant alkyl phosphate lipid (amphiphilic compound) and mRNA, for intracellular delivery as taught by Le Corre in view of Guild. One of ordinary skill would have been motivated to do so because Le Corre’s discloses their amphiphilic compound 7; further because Guild’s teaches that liposomes are typically formed by amphiphilic molecules, such as lipids of synthetic or natural origin that comprise spatially separated hydrophilic and hydrophobic domains, and that liposomes are useful in medicine, particularly for their use as transfer vehicles of diagnostic or therapeutic compounds in vivo. One of ordinary skill would have had a reasonable expectation of success in doing so in view of Le Corre’s teachings of compound 7 and methods of formulating liposomes; further in view of Guild’s teachings of lipid nanoparticle compositions comprising one or more non-cationic lipids, PEG-modified lipids and cholesterol; Guild’s methods of mRNA delivery; and Guild’s teachings that the properties of the transfer vehicle (e.g., size, charge and/or pH) may be optimized to effectively deliver transfer vehicle to the target cell, reduce immune clearance and/or promote retention in that target cell. A person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2143(E) KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007).
Regarding claim 32, Guild teaches their pharmaceutical compositions comprise a transfer vehicle, such as pharmaceutically acceptable carriers (col. 9, lines 5-10).
Regarding claims 36-42, Guild discloses delivery of mRNA (reading on RNA, polynucleotides, and agent).
Response to Arguments
Claims
Claim amendments are acknowledged. No new matter has been introduced.
Claim Rejections - 35 USC § 112(b)
Applicant’s arguments, see page 7, filed 01/26/2026, with respect to the rejection(s) of the claims under 35 USC § 112(b) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of new claims added.
Claim Rejections - 35 USC § 102
Applicant’s arguments, see page 7, filed 01/26/2026, with respect to the rejection(s) of the claims under 35 USC § 102 have been fully considered and are persuasive. Therefore, the 35 USC § 102 rejection of the claims has been withdrawn.
Claim Rejections - 35 USC § 103
Applicant's arguments filed 01/26/2026 have been fully considered but they are not persuasive.
Applicant argues the Office has not shown cited references disclose all the limitations of the independent claims, and states that Le Corre and Guild fail to disclose or suggest the claimed compositions and nanoparticles for delivering an agent into a cell. Applicant argues that compound 7 is “merely an intermediate molecule used in the synthesis of a cationic lipophosphate” and not to be used in compositions for mRNA delivery. Applicant argues that Guild provides lipid nanoparticles using unrelated compounds and fails to remedy the deficiencies of Le Corre. Applicant asserts one of ordinary skill would have no reason to use compound 7 in the formulation for mRNA delivery to a cell and cites MPEP 2144.09 (VI).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to Applicant’s arguments that the Office has not shown cited references disclose all the limitations of the independent claims; Applicant is advised that “[A] prior art reference must be considered in its entirety, i.e., as a whole” W.L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983) (see MPEP 2141.02 VI). Thus, while the rejections listed above present a modified interpretation of the teachings of the previously cited prior solely for the purpose of clarity, the claims remain rejected over the prior art of record.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Le Corre discloses the elected compound 7 below, [which one of ordinary skill in the art would appreciate is a non-cationic, amphiphilic compound] (Scheme 1(B), page 8043).
PNG
media_image1.png
141
262
media_image1.png
Greyscale
, wherein the Olelyl group is defined as:
PNG
media_image2.png
48
630
media_image2.png
Greyscale
Guild discloses lipid nanoparticle compositions and methods of mRNA delivery (title and abstract). Guild specifically discloses compositions and methods for intracellular delivery of mRNA in a liposomal transfer vehicle (col. 3, lines 24-26). Guild discloses their mRNA is formulated in a liposomal transfer vehicle may comprise one or more non-cationic lipids, PEG-modified lipids, and may further comprise cholesterol (col. 4, lines 15-17). Guild teaches liposomes (e.g., liposomal lipid nanoparticles) are generally useful in a variety of applications in research, industry, and medicine, particularly for their use as transfer vehicles of diagnostic or therapeutic compounds in vivo (col. 14, lines 31-35), and that liposomes are typically formed by amphiphilic molecules, such as lipids of synthetic or natural origin that comprise spatially separated hydrophilic and hydrophobic domains (col. 14, lines 40-43).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to prepare a composition comprising Le Corre’s amphiphilic compound and mRNA; or a nanoparticle comprising the instant alkyl phosphate lipid (amphiphilic compound) and mRNA, for intracellular delivery as taught by Le Corre in view of Guild. One of ordinary skill would have been motivated to do so because Le Corre’s discloses their amphiphilic compound 7; further because Guild’s teaches that liposomes are typically formed by amphiphilic molecules, such as lipids of synthetic or natural origin that comprise spatially separated hydrophilic and hydrophobic domains, and that liposomes are useful in medicine, particularly for their use as transfer vehicles of diagnostic or therapeutic compounds in vivo. One of ordinary skill would have had a reasonable expectation of success in doing so in view of Le Corre’s teachings of compound 7 and methods of formulating liposomes; further in view of Guild’s teachings of lipid nanoparticle compositions comprising one or more non-cationic lipids, PEG-modified lipids and cholesterol; Guild’s methods of mRNA delivery; and Guild’s teachings that the properties of the transfer vehicle (e.g., size, charge and/or pH) may be optimized to effectively deliver transfer vehicle to the target cell, reduce immune clearance and/or promote retention in that target cell.
In response to Applicant’s arguments that Le Corre teaches their compound 7 as an intermediate, and the citation of MPEP 2144.09 (VI) – this section of the MPEP also states “If the prior art does not teach any specific or significant utility for the disclosed compounds, then the prior art is unlikely to render structurally similar claims prima facie obvious in the absence of any reason for one of ordinary skill in the art to make the reference compounds or any structurally related compounds. In re Stemniski, 444 F.2d 581, 170 USPQ 343 (CCPA 1971).”
However, the prior art of record does in fact provide specific utility for the disclosed compound. Guild specifically states their nanoparticles comprise non-cationic lipids, which one of ordinary skill in the art would immediately know compound 7 is a non-cationic lipid. Furthermore, Guild teaches that liposomes are typically formed by amphiphilic molecules, such as lipids of synthetic or natural origin that comprise spatially separated hydrophilic and hydrophobic domains (col. 14, lines 40-43). One of ordinary skill would also appreciate compound 7, more than a “mere intermediate” is also an amphiphilic non-cationic lipid.
In response to Applicant’s arguments that Guild is referring to “unelated compounds”; Applicant is advised that MPEP 2143 (I)(B) states that: “substitution of one known element [a non-cationic lipid in the instant case] for another yields predictable results to one of ordinary skill in the art.”
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
Examiner interviews are available via telephone 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, Kortney L. Klinkel can be reached at (571) 270-5239. 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.
/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627