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 .
DETAILED ACTION
Claim status
Claims 1-4, 6, 8, 10, 13-14, 26-30, 48, 57-59, and 62 are pending
Claims 48, 57-59, and 62 are withdrawn
Claims 1-4, 6, 8, 10, 13-14, 26-30 are under examination
Election/Restrictions
Applicant’s election of the following invention without traverse in the reply filed on 3/16/2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Group I, claims 1-4, 6, 8, 10, 13-14, 26-30, and 48, drawn to a composition comprising a proteolipid vesicle and therapeutic cargo.
Claims 57-59, and 62 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Applicant’s election of the following species is acknowledged.
DODAP as the ionizable lipid;
pDNA as the therapeutic cargo.
Claim 48 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic claim.
Priority
The instant application was filed 3/31/2023 and is a national stage entry of PCT/CA2021/051377 filed 10/1/2021 and claims foreign priority to application CA3094859, filed 10/01/2021.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed foreign application, Application No. CA3094859, fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. Review of the application No. CA3094859 did not reveal support for bombesin attached to the C-terminus of the FAST protein or chimera thereof. Thus the instant claim 26 is being given the filing date of 10/01/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 3/31/2023, 12/13/2023, and 3/16/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112(b)
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 2, 6, 8, 10, 13, 14, and 26-30 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 pre-AIA the applicant regards as the invention.
Claim 2 recites the terms “DOTMA”, “18:1 EPC”, “DOTAP”, “DDAB”, “18:0 EPC”, and “18:0 TAP” are used by the claim to be an “ionizable lipid”, while the accepted meanings of these terms are as “non-ionizable lipids”. In other words, these cationic lipids comprise a quaternary amine that is permanently positively charged. The term is indefinite because the specification does not clearly redefine the terms. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999).
Claim 6 is dependent on canceled Claim 5. MPEP 608.01(n) states that if the base claim has been canceled, a claim which is directly or indirectly dependent thereon should be rejected as incomplete. Furthermore, instant Claim 6 is indefinite for a lack of antecedent bases for limitations which are not presented in the canceled claim upon which it is dependent. For the sake of compact prosecution, Claim 6 is being examined as being dependent on Claim 4.
Claim 8 recites the phrase "further comprising a therapeutic cargo" in regard to the proteolipid vesicle with an ionizable lipid to therapeutic cargo molar ratio of 2.5:1 to 20:1 in Claim 1. There is insufficient antecedent basis for this limitation in the claim because Claim 1 already comprises a therapeutic cargo, thereby rendering Claim 8 indefinite as to which therapeutic cargo is encompassed by the scope of the claim. Dependent Claims 10, 13, 14, and 26 are included in the basis of this rejection as depending on Claim 8, but not clarifying the scope of the therapeutic cargo.
Claim 27 recites the phrase "a therapeutic cargo" in regard to the proteolipid vesicle with an ionizable lipid to therapeutic cargo molar ratio of 2.5:1 to 20:1 in Claim 1. There is insufficient antecedent basis for this limitation in the claim because Claim 1 already comprises a therapeutic cargo, thereby rendering Claim 26 indefinite as to which therapeutic cargo is encompassed by the scope of the claim. Dependent Claims 28-30 are included in the basis of this rejection as depending on Claim 27, but not clarifying the scope of the therapeutic cargo.
Appropriate correction is required.
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 of this title, 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 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 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 1-4, 6, 8, 10, 13-14, 27-29 are rejected under 35 U.S.C. 103 as being unpatentable over Scholz, (WO2019/204666, filed 4/18/2019, published 10/24/2019, see IDS filed 12/13/2024) in view of Cui et al. (WO2010/135207, filed 5/16/2010, published 11/25/2010)
In regard to claim 1, Scholz teaches and claims a lipid nanoparticle (LNP) for delivering an expression construct for the production of a therapeutic agent in a cell comprising:
a lipid nanoparticle comprising the ionizable lipid of DODAP;
a fusogenic p14 and/or p15 FAST protein,
a polynucleotide expression construct comprising encoding a therapeutic protein operably linked to a promoter ([0030-0035], claims 1, 8, 18 & 19 of Scholz).
However, Scholz is silent to the molar ratio of ionizable lipid to polynucleotide expression construct.
Cui teaches and claims a lipid nanoparticle (LNP) for delivering an expression construct for the production of a therapeutic protein in a cell comprising:
a lipid nanoparticle comprising the ionizable lipid of DODAP;
a polynucleotide comprising a nucleic acid sequence encoding a therapeutic agent;
wherein the molar ratio of cationic lipid to polynucleotide is between 2:1 to 10:1 (Summary, 1st para., see claims 1-6 of Cui) .
Accordingly, it would have been obvious to prepare the proteolipid vesicle comprising the ionizable lipid DODAP, the FAST protein, and polynucleotide as taught by Scholz, and choose a cationic lipid to polynucleotide ratio of between 2:1 to 10:1 as taught by Cui with a reasonable expectation of success. Furthermore, since Scholz teaches that the DODAP is the predominant lipid of the cationic lipids (e.g., 45:15 or 55:10 mole % ratio), the corrected ionizable lipid to polynucleotide ratio would be slightly less than the 10:1 range taught by Cui but still within the claimed range (e.g., 7.5:1 or 8.5:1 mole % ratio). One of ordinary skill would have been motivated to choose these molar ratios since it has been held that 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. In re Aller, 105 USPQ 233.
In regard to claims 2 and 3, as stated supra, Scholz teaches the ionizable lipid DODAP.
In regard to claim 4, Scholz teaches p14 FAST protein and the p14/p15 chimeric FAST protein (see Claims 18-19 of Scholz).
In regard to claim 6, as states supra, Scholz teaches the p14/p15 chimeric FAST protein of SEQ ID NO:17 (see Claim 19 of Scholz).
In regard to claims 8, 10, and 27-29, Scholz teaches the therapeutic cargo is a polynucleotide such as a plasmid DNA encapsulated in the LNP (Fig. 1-2, [0017].
In regard to claim 13, as state supra, Scholz in view of Cui make obvious molar ratio of about 10:1. Furthermore, as stated supra, in some embodiments, Scholz teaches that the ionizable lipid is the only cationic lipid thereby resulting in a 10:1 ratio, while in other embodiments the ionizable lipid is the principle cationic lipid, which would reduce the ionizable mole % ratio (e.g., a 45%/15% mole ratio of DODAP/DOTAP for total cationic lipids, would reduce the ionizable lipid molar ratio to polynucleotide from 10:1 to 7.5:1). Again, the choosing of these molar ratios would have been obvious for optimization or workable ranges since the general conditions of the claim are disclosed by Scholz in view of Cui.
In regard to claim 14(a), Scholz teaches the LNP comprises the ionizable lipid DODAP, as well as two or more lipids selected from DOTAP, DOPE, and DMG-PEG (see Claims 8-11 of Scholz).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 14 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Scholz, (WO2019/204666, filed 4/18/2019, published 10/24/2019, see IDS filed 12/13/2024) in view of Cui et al. (WO2010/135207, filed 5/16/2010, published 11/25/2010), as applied to claims 1, 4, 6, 8, 10, 13, 27-29, in further view of Thomas et al (WO2018/064755, filed 10/02/2017, published 4/12/2018)
As stated supra, Scholz in view of Cui suggest a proteolipsome comprising the ionizable lipid of DODAP; a fusogenic p14 and/or p15 FAST protein, a polynucleotide expression construct comprising encoding a therapeutic protein, wherein the molar ratio of cationic lipids to polynucleotide is between 2:1 to 10:1.
In regard to claim 14(h) and claim 30(i), as stated supra, Scholz teaches the LNP comprises the ionizable lipid DODAP, as well as two or more lipids selected from DOTAP, DOPE, and DMG-PEG (see Claims 8-11 of Scholz).
However, although Scholz suggests a mole ratio among the lipids of 10% DOTAP:55% DODAP:30% DOPE:4% DMG-PEG, they are silent to 6% DOTAP:60% DODAP:30% DOPE:4% DMG-PEG at a ionizable lipid to pDNA ratio of about 10:1.
Thomas teaches compositions and methods of using LNP comprising a cationic lipid such as DODAP, as well as a structural lipid such as DOPE and stabilizing agent such as a DMG-PEG. Specifically, Thomas teaches the cationic lipid is at 60 mol % (p. 2, Summary of the Invention, see Claims 1-3, and 8-11 of Thomas).
Accordingly, it would have been obvious to prepare the proteolipid vesicle comprising 10% DOTAP:55% DODAP:30% DOPE:4% DMG-PEG, as taught by Scholz, and substitute 60 mol % of DODAP as taught by Thomas with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so as taught by Thomas, because increasing the ratio of cationic lipid to structural lipid in the lipid nanoparticle allows better transfection of hard to transfect “resistant” cell types such as neurons and related cell types (Abstract, p. 7, 2nd para.), which would have been important for using the composition of Scholz et al to treat brain tissue and cancers (see [0014, 0072, 0089, 0110, 0164] of Scholz). As far as lowering the mol % of DOTAP from 10 mol % to about 5 mol % (i.e., 6 mol %), since the DODAP was increased by about 5 mol %, it would have been obvious to decrease the DOTAP by about 5 mol % to keep the ratio of total cationic lipids to neutral lipids about the same. Furthermore, as per the ionizable lipid to polynucleotide ratio of about 5:1 to 15:1, as stated supra, since Scholz et al. teach that the DODAP is the predominant lipid of the total cationic lipids (e.g.,60:5 mole % ratio), thus the ionizable cationic lipid to polynucleotide ration would be slightly less than the range of 10:1 taught by Cui but still within the claimed range (e.g., about 9.2:1). One of ordinary skill would have been motivated to choose these molar ratios since it has been held that 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. In re Aller, 105 USPQ 233.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Scholz, (WO2019/204666, filed 4/18/2019, published 10/24/2019, see IDS filed 12/13/2024) in view of Cui et al. (WO2010/135207, filed 5/16/2010, published 11/25/2010), as applied to claims 1, 4, 6, 8, 10, 13, in further view of Mriouah et al. (Cancer Res, 2017, 77(Sup 13): Abstract 5143)
As stated supra, Scholz in view of Cui suggest a proteoliposome comprising the ionizable lipid of DODAP; a fusogenic p14 and/or p15 FAST protein, a polynucleotide expression construct comprising encoding a therapeutic protein, wherein the molar ratio of cationic lipids to polynucleotide is between 2:1 to 10:1.
In regard to claim 26, although Scholz teaches the LNP are to deliver their cargo to prostate cancer cells (e.g., human PC-3 cells) [0014, 0072, 0089, 0110], Examples, 1 and 4, see Figs. 8, 36-54), and suggests a targeting ligand on the surface of the LNP [0084], they are silent to the p14/p15 fusion further comprising a bombesin peptide.
Mriouah teaches a proteoliposome comprising a p14 FAST protein further comprising a bombesin peptide.
Accordingly, it would have been obvious to prepare the proteolipid vesicle comprising the ionizable lipid DODAP, the FAST protein, and polynucleotide at a ionizable lipid to polynucleotide ratio of between 2:1 to 10:1 as suggested by Scholz in view of Cui and combine a bombesin peptide as taught by Mriouah with a reasonable expectation of success. One of ordinary skill would have been motivated to combine the bombesin peptide as taught by Mriouah because the bombesin peptide targets the proteoliposome to the GRP receptor overexpressed on prostate cancer cells.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-4, 6, 8, 10, 13-14, 27-30 are rejected on the grounds of nonstatutory double patenting over claims 1-20 of U.S. Patent No. 11,603,543 (Common inventor of Lewis, Patented 3/14/2023), in view of Cui et al. (WO2010/135207, filed 5/16/2010, published 11/25/2010)
The subject matter claimed in the instant application is disclosed in the referenced patent as follows: the proteolipid composition comprising at least 35 mole % DODAP, about 30 mole % DOPE, about 4 mole % DMG-PEG, a p14e15 FAST protein, and a polynucleotide expression vector of cited patent makes obvious the proteolipid composition of instant application. It is clear that elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the instant claims are more specific to the molar ratio of ionizable lipid to polynucleotide.
Nevertheless, Cui teaches and claims a lipid nanoparticle (LNP) for delivering an expression construct for the production of a therapeutic protein in a cell comprising:
a lipid nanoparticle comprising the ionizable lipid of DODAP;
a polynucleotide comprising a nucleic acid sequence encoding a therapeutic agent;
wherein the molar ratio of cationic lipid to polynucleotide is between 2:1 to 10:1 (Summary, 1st para., see claims 1-6 of Cui) .
Accordingly, it would have been obvious to prepare the proteolipid vesicle comprising the ionizable lipid DODAP, the FAST protein, and polynucleotide as claimed by cited patent, and choose a cationic lipid to polynucleotide ratio of between 2:1 to 10:1 as taught by Cui with a reasonable expectation of success. One of ordinary skill would have been motivated to claim these molar ratios since it has been held that 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. In re Aller, 105 USPQ 233.
Furthermore, in regard to claim 14(i) and claim 30(k), as stated supra, the cited patent claims at least 35 mole % DODAP, but also claim 30 mole % DOPE, and 4 mole % DMG-PEG, which mathematically results in 66 mole % DODAP as an obvious percentage to claim. One of ordinary skill would have been motivated to choose these molar ratios since it has been held that 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. In re Aller, 105 USPQ 233.
Since the instant application claims are obvious over cited patent claims in view of Cui, said claims are not patentably distinct.
Claim 26 is rejected on the grounds of nonstatutory double patenting over claims 1-20 of U.S. Patent No. 11,603,543 (Common inventor Lewis, Patented 3/14/2023), in view of Cui et al. (WO2010/135207, filed 5/16/2010, published 11/25/2010), as applied to claims 1, 4, 6, 8, 10, 13, in further view of Mriouah et al. (Cancer Res, 2017, 77(Sup 13): Abstract 5143)
The subject matter claimed in the instant application is disclosed in the referenced patent as follows: the proteolipid composition comprising at least 35 mole % DODAP, about 30 mole % DOPE, about 4 mole % DMG-PEG, a p14e15 FAST protein, and a polynucleotide expression vector at a 2:1 to 10:1 ionizable lipid to polynucleotide of cited patent makes obvious the proteolipid composition of instant application. It is clear that elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the instant claims are more specific to further including a bombesin peptide.
Nevertheless, Mriouah teaches a proteoliposome comprising a p14 FAST protein further comprising a bombesin peptide.
Accordingly, it would have been obvious to prepare the proteolipid vesicle comprising the ionizable lipid DODAP, the FAST protein, and polynucleotide as claimed by cited patent in view of Cui and combine a bombesin peptide as taught by Mriouah with a reasonable expectation of success. One of ordinary skill would have been motivated to combine the bombesin peptide as taught by Mriouah because the bombesin peptide targets the proteoliposome to the GRP receptor overexpressed on prostate cancer cells.
Since the instant application claims are obvious over cited patent claims in view of Cui and Mriouah, said claims are not patentably distinct.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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