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 .
Receipt is acknowledged of Applicant’s Restriction Requirement Response filed on 09/16/2025; and IDS filed on 06/02/2025.
Claims 197-200, 203, 205, 217, 220, 222, 224, 237, 242, 250-251, 254, 257, 259, 261, 264, 268-270, 273, 281, 283-284, 291, 293-294, 296 are pending in the instant application.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 197-200, 203, 205, 217, 220, 222, 224, 237, 242, 250-251, 254, 257, 259, 261, 264, 268-270, 273, 281, 283-284, 291, 293-294 and 296 are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. Patent No. 12,453,706 in view of LUTTEROPP et al (US 2016/0144026).
The patent recites a stealth lipid nanoparticle (LNP) comprising: (a) a therapeutic nucleic acid (TNA); (b) an ionizable lipid; (c) a sterol; (d) a first lipid-anchored polymer comprising a first hydrophilic polymer and a first lipid-linker, wherein the first lipid-linker comprises a first lipid comprising at least two hydrophobic tails, and wherein each hydrophobic tail comprises a carbon chain having 18 carbon atoms (C.sub.18); (e) a second lipid-anchored polymer comprising a second hydrophilic polymer, a second lipid-linker, and a first reactive moiety conjugated to a first targeting moiety; wherein the second lipid-linker comprises a second lipid comprising at least two hydrophobic tails, wherein each hydrophobic tail comprises a carbon chain having 18 carbon atoms (C.sub.18); and wherein the targeting moiety is a variable heavy chain-only antibody (VHH) or a single-chain antibody (scFv); and (f) a third lipid-anchored polymer comprising a third hydrophilic polymer, a third lipid-linker, and a second reactive moiety conjugated to a second targeting moiety; wherein the third lipid-linker comprises a third lipid comprising at least two hydrophobic tails, wherein each hydrophobic tail comprises a carbon chain having 18 carbon atoms (C.sub.18); and wherein the second targeting moiety is a variable heavy chain-only antibody (VHH) or a single-chain antibody (scFv); wherein the first targeting moiety and the second targeting moiety are different; wherein the first targeting moiety and the second targeting moiety are each cell-type specific targeting moieties, wherein the cell-type is a hematopoietic stem cell (HSC), wherein the molecular weight of each of the second and third hydrophilic polymers is greater than the molecular weight of the first hydrophilic polymer; wherein the first lipid-anchored polymer, the second lipid-anchored polymer, and the third lipid-anchored polymer are present at a combined molar percentage of about 2% to about 5%, and wherein the second lipid-anchored polymer and the third lipid-anchored polymer are present at a combined molar percentage of about 0.01% to about 0.5%; optionally wherein the stealth LNP comprises about 5 to 400 total targeting moieties (see claim 1).
The patent does not teach targeting moiety binding to an immune effector cell, such as T-cell.
LUTTEROPP teaches the prior art had known of treating diseases by targeting hematopoietic stem cells and T cells (see [0056]).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate targeting moiety binding to an immune effector cell, such as T-cell. The person of ordinary skill in the art would have been motivated to make those modifications, because the incorporation would target additional diseases, and reasonably would have expected success because both references are in the same field of endeavor, such as the pharmaceutical industry.
Claim Rejections - 35 USC § 112, 1st paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 220, 259, 270 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claims 220, 259 and 270, the term “derivatives” does not meet the written description provision of 35 USC § 112, first paragraph, due to lacking chemical structural information for what they are and chemical structures are highly variant and encompass a myriad of possibilities. The specification provides insufficient written description to support the genus of derivatives encompassed by the claim, since there is no description of the structural relationship of these derivatives provided in the specification and Applicant has not provided a description as to how the base molecule may be changed while remaining a derivative.
Claim Rejections - 35 USC § 112, 2nd 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 200, 237, 270 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 200 contain the term "OMe", which is not defined by the claims. Claims must stand alone to define the invention, and should not rely on the description or the drawings to give them meaning (see Ex Parte Fressola, 27 USPQ 2d 1608). Thus, claim 200, at the very least, should define "OMe" by its formal chemical name; once "OMe" is defined, the term "OMe" may be subsequently recited. If needed, see Applicant’s claim 199 as a proper example for “PEG”.
Claims 237 contain the terms "CD3, CD4, CD5, CD6, CD7, CD8, CD9, CD10, CD11, and PD-1", which is not defined by the claims. Claims must stand alone to define the invention, and should not rely on the description or the drawings to give them meaning (see Ex Parte Fressola, 27 USPQ 2d 1608). Thus, claim 237, at the very least, should define "CD3, CD4, CD5, CD6, CD7, CD8, CD9, CD10, CD11, and PD-1" by its formal chemical name; once "CD3, CD4, CD5, CD6, CD7, CD8, CD9, CD10, CD11, and PD-1" is defined, the term "CD3, CD4, CD5, CD6, CD7, CD8, CD9, CD10, CD11, and PD-1" may be subsequently recited.
Regarding claim 270, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 112, 4th paragraph
The following is a quotation of the fourth paragraph of 35 U.S.C. 112:
Subject to the [fifth paragraph of 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 250 is rejected under 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 250 recites limitations that are already in independent claim 197. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
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.
Claim(s) 197-200, 203, 205, 217, 220, 222, 224, 237, 242, 250-251, 254, 257, 259, 261, 264, 268-270, 273, 281, 283-284, 291, 293-294 and 296 is/are rejected under 35 U.S.C. 103 as being unpatentable over XU et la (CN113908292, wherein a machine translation is provided; see IDS filed on 06/02/2025 for Chinese original) in view of GANGLUFF et al (WO 2023/148276) and MO et al (US 2016/0250352).
Regarding claims 197-200, 203, 205, 2017, 220, 222, 224, 237, 242, 250-251, 254, 257, 259, 261, 264, 268, 270, 273, 284, 291, 293-294, 296 XU teaches lipid nanoparticles (“NLP”; see [n0003]) comprised of:
therapeutic nucleic acid, such as nucleic acid (see [n0044]), such as small interfering RNA (siRNA; see [0003]);
ionizable lipid (see [n0005]), such as Dlin-MC3-DMA (see [n0026]);
a sterol, such as cholesterol (see [n0015]);
PEG (see [n0007]), which reads on first hydrophilic polymer; DSPE (see [n0007]), which reads on first lipid-linker. Note, Applicant’s claims 203 and 217 recite first, second, and third hydrophilic polymers and lipid-linker are the same.
PEG (see [n0007]), which reads on second hydrophilic polymer; DSPE (see [n0007] and [n0042]) or DSG (see [n0042]), which reads on second lipid-linker; active group, such as maleimide (see [n0007]), which reads on first reactive moiety; targeting moiety, such as Transferrin (“Tf”; see [n0007]; and [n0014]) and antibodies (see [n0043]), such as scFv fragments (see [n0043]) or single-domain antibodies (see [n0043]), which is a variable heavy chain-only antibody.
PEG (see [n0007]), which reads on third hydrophilic polymer; DSPE (see [n0007]; and [n0042]) or DSG (see [n0042]), which reads on third lipid-linker; active group, such as maleimide (see [n0007]), which reads on first reactive moiety; targeting moiety, such as Transferrin (“Tf”; see [n0007]; and [n0014]) and antibodies (see [n0043]), such as scFv fragments (see [n0043]) or single-domain antibodies (see [n0043]), which is a variable heavy chain-only antibody.
XU further teaches reducing/adjusting the amount of Tf-PEG2K-DMG to obtain a stable LNP structure (see [n0120]); and reducing material waste in the preparation process and reducing production costs (see [n0012]).
XU does NOT teach (1) the first and second targeting moieties are different and binds to a T cell specific antigen; and (2) the molecular weight of the second and third hydrophilic polymers are greater than the first hydrophilic polymer, such as PEG2000 and PEG5000.
GANGLUFF teaches methods for targeted delivery of nucleic acid, such as RNA to cells (see abstract; pg. 1), with lipid nanoparticles (“LNP” (see pg. 118) by using a primary targeting moiety and further binding moiety to the binding moiety of the connector compound (see pg. 1), which reads on the first and second targeting moieties are different. Targeting antigen on immune effector cells (see pg. 1), wherein the antigen receptor such as T cell receptor (see pg. 140), such as CD3 (see pg. 3). Additional disclosures include: the antibody or antibody derivative comprises a VHH domain (see pg. 10) or scFv (see pg. 14); increased amounts to be targeted by the methods (see pg. 138).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate the (1) first and second targeting moieties are different and binds to a T cell specific antigen. The person of ordinary skill in the art would have been motivated to make those modifications, because the incorporation would increase amounts to be targeted, and reasonably would have expected success because both references are in the same field of endeavor, such as lipid nanoparticles with targeting moieties.
MO teaches shielded biologic therapeutic nanoparticles (see title and abstract) to increase circulation half-life of biologic therapeutics (see [0002]) by using short polymer chains with long polymer chains, such as molecular weight of 2kD and 5kD (see [0042]-[0044]), wherein the polymer is PEG (see [0040]).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate (2) PEG2000 and PEG5000. The person of ordinary skill in the art would have been motivated to make those modifications, because the incorporation would increase circulation half-life of the therapeutic, and reasonably would have expected success because both references are in the same field of endeavor, such as the pharmaceutical industry.
The references do not specifically teach adding the ingredients in the amounts claimed by Applicant. 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, such as having stable lipid nanoparticles, decreasing cost of materials, increase targeting to targeted sites, etc. Thus, absent some demonstration of unexpected results from the claimed parameters, this optimization of ingredient amount would have been obvious at the time of Applicant's invention.
Regarding claims 198-200, XU teaches PEG2K (see [n0042]), which is PEG2000, wherein MO teaches PEG2000 and PEG5000.
Regarding claim 237, GANGLUFF teaches the immune effector cells are CD3 (see pg. 3)
Regarding claim 259 and 261, XU teaches 38.5% cholesterol (see [n0074]).
Regarding claim 264, XU teaches ionizable lipid (see [n0005]), such as Dlin-MC3-DMA (see [n0026]).
Regarding claim 268, XU teaches 50% Dlin-MC3-DMA.
Regarding claims 269 and 270, XU teaches 10% DSPC (see [n0026]), which reads on helper lipid.
Regarding claim 273, XU teaches active groups can be maleimide or thiol (see [n0007]).
Regarding claim 281, XU teaches the diameter should not exceed 150nm (see [n0004]), wherein particle sizes include 80nm (see original document Table 1 at [0079]).
Regarding claim 283, XU teaches mRNA encodes protein (see [n0051]).
Regarding claim 284, XU teaches nucleic acid drugs include small interfering RNA (siRNA) and messenger RNA (mRNA) (see [n0003]).
Regarding claim 291, the prior art’s lipid nanoparticle would have the same chemical/physical properties, such as half-life in blood, as claimed by Applicant, because the prior art’s lipid nanoparticle has the same ingredients as claimed by Applicant.
Telephonic Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAKE MINH VU whose telephone number is (571)272-8148. The examiner can normally be reached Mon-Fri 9:00am-5:30pm.
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/JAKE M VU/Primary Examiner, Art Unit 1618