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 .
Election/Restrictions
Applicant’s election without traverse of Group I (i.e., Claims 1-20, drawn to an aqueous compositing comprising a population of HDL mimetic micellular nanoparticles) in the reply filed on 11/06/2025 is acknowledged. Additionally, Applicant’s representative (i.e., Michael Curts) confirm the election without traverse of Species A (i.e., a single and specific amphiphilic, alpha-helical peptide indicating: single and specific SEQ ID NO, Applicant’s Election: SEQ ID NO: 35; and a single and specific paclitaxel-anchor moiety from Table 6, Applicant’s Election: moiety No. 78, i.e., Paclitaxel-γ-tocotrienol conjugate with a cleavable carbonate bond) during a telephonic call on 11/21/2025.
Claims 21-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, likewise claims 16-18 and 20 are withdrawn from further consideration as being drawn to a nonelected species; there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/06/2025.
Upon searching the elected species (i.e., moiety No. 78, i.e., Paclitaxel-γ-tocotrienol conjugate with a cleavable carbonate bond)), additional species were found, e.g., moiety No. 71 (i.e., paclitaxel-cholesterol conjugate with a cleavable carbonate bond) and moiety No. 79 (i.e., paclitaxel-δ-tocotrienol with a cleavable carbonate bond). Accordingly, for purposes of compact prosecution, the election of species is modified only to the extent of examining these additional species. Otherwise the election of species requirement is still retained.
Claim Status
Claims 1-30 were originally filed on 05/09/2025.
The amendment filed on 03/16/2026, cancelling all claims drawn to the elected invention (i.e., claims 1-30) and presenting only claims drawn to a non-elected invention (i.e., new claims 31-47), was not entered.
The amendment filed on 06/15/2026, renumbered duplicate claim 15 as claim 16; and also renumbered subsequent claims accordingly. Additionally, claims 1-8, 10, and renumbered claims 20 and 22-30 were cancelled. Per MPEP 608.01(j), the original number of the claims must be preserved throughout the prosecution. Applicants’ representative was made aware of the renumbering issue and thus filed a new claim set, with the appropriate corrections.
The amendment filed on 07/01/2026 cancelled original claims 1-8, 10, 19, 21-29 and duplicate claim 15; and added new claim 30.
Note: Applicants have inadvertently set the claim status identifier for original claim 15 and for new claim 30 as “withdrawn”. However, original claim 15 and “new” claim 30 were previously examined and cannot be withdrawn because these claims are not drawn to a non-elected invention nor to a non-elected species. Appropriate correction is required.
Claims 9, 11-15, 16-18, 20 and 30 are currently pending; and claims 9, 11-15 and 30 are under consideration.
Sequence Interpretation
The scope of “an amphiphilic alpha-helical peptide” is interpreted as open-ended requiring 100% identity to SEQ ID NO: 35 with any N-/-C terminal additions. Per MPEP 2111.03(I), the transitional phrase “comprising”, which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. Thus a sequence that comprises DVFQKLAibELFNQLAibEKWKQV (i.e., SEQ ID NO: 35), with any N-/-C terminal additions would read on the instantly claimed an amphiphilic alpha-helical peptide.
Priority
The present application claims the benefit under 35 U.S.C 119 (e) to U.S. Provisional Application No. 63/645,127 filed 05/09/2024. 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.
Response to Arguments
1. Applicant’s arguments, see Remarks, filed 07/01/026, with respect to the objection to the specification (i.e., paragraph [0302] at pg. 87), have been fully considered and is persuasive. The objections to the specification have been withdraw.
2. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to the objection claims 1-29 (i.e., acronym), have been fully considered and is persuasive. The objections to claims 1-29 have been withdraw.
3. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to the objection claim 15 (i.e., duplicate claim numbering), have been fully considered and is persuasive. The objection to duplicate claim 15 is moot.
4. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to the objection claim 19 (i.e., grammar), have been fully considered and is persuasive. The objection to claim 19 is moot.
5. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to 35 U.S.C. 112(b) rejection to claims 1-15, duplicate claim 15 and duplicate claim 19 as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention (i.e., ambiguity regarding naturally occurring HDL); have been fully considered and are persuasive. The 35 U.S.C. 112(b) rejection of claims 1-15, duplicate claim 15, and 19, has been withdrawn.
6. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to 35 U.S.C. 112(b) rejection to claims 1-15, duplicate claim 15, and claim 19, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention (i.e., ambiguity regarding anchor moiety); have been fully considered and are persuasive. The 35 U.S.C. 112(b) rejection of claims 1-15, duplicate claim 15 and 19, has been withdrawn.
7. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to 35 U.S.C. 112(b) rejection to claims 10 and 14 as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention (i.e., ambiguity regarding “about”); have been fully considered and are persuasive. The 35 U.S.C. 112(b) rejection of claims 10 and 14 has been withdrawn.
8. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to 35 U.S.C. 112(b) rejection to original claim 15 as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention (i.e., Table 6); have been fully considered but are not persuasive. The 35 U.S.C. 112(b) rejection of original claim 15 has been maintained.
9. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to 35 U.S.C. 112(b) rejection to duplicate claim 15, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention (i.e., ß-, γ-, and δ anchor moieties); have been fully considered and are persuasive. The 35 U.S.C. 112(b) rejection of duplicate claim 15 is moot.
10. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to 35 U.S.C. 112(a) rejection to claims 1-15 and duplicate claim 15, as failing to comply with the written description requirement; have been fully considered and are persuasive. The 35 U.S.C. 112(a) rejection of claims 1-15 and duplicate claim 15 has been withdrawn.
11. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to 35 U.S.C. 102(a)(1) rejection to claims 1, 3-6 and 8, as being anticipated by US 2011/0020242 A1 Pub. Date: Jan. 27, 2011 (herein after “Zheng et al.”); have been fully considered and are persuasive. The 35 U.S.C. 102(a)(1) rejection of claims 1, 3-6 and 8 is moot.
12. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to 35 U.S.C. 102(a)(1) rejection to claims 1-3 and 6-8, as being anticipated by US 10,532,105 B2. Date of Patent: Jan. 14, 2020 (herein after “Homan et al.”); have been fully considered and are persuasive. The 35 U.S.C. 102(a)(1) rejection of claims 1-3 and 6-8 is moot.
13. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to 35 U.S.C. 103 rejection to claims 9-15, duplicate claim 15, and 19; have been fully considered but are not persuasive. The 35 U.S.C. 103 rejection of claims 9-15, duplicate claim 15, and 19, has been maintained.
14. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to the Double Patenting Rejections, have been fully considered but are not persuasive. The Double Patenting Rejection over copending Application No. 19/204,092, has been maintained.
15. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to the Double Patenting Rejections, have been fully considered but are not persuasive. The Double Patenting Rejection over copending Application No. 18/041,289, has been maintained.
16. Applicant’s arguments, see Remarks, filed 07/01/2026, with respect to the Double Patenting Rejections, have been fully considered but are not persuasive. The Double Patenting Rejection over U.S. Patent No. 10,532,105 B2 (Application number 15/743,098); has been maintained.
New Rejections
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.
1. Claims 15 is 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 15 recites the limitation "wherein the paclitaxel-anchor moiety" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 15 further limits claim 13, which is silent about the “paclitaxel-anchor moiety”. Likewise, parent claim 9 recites that the population of chemotherapeutic HDL mimetic micellular nanoparticles comprise: (c) a conjugate comprising γ-tocotrienol and paclitaxel. Therefore, antecedent claims 9 and 13 do not make reference to an anchor moiety, thereby an ordinary skilled artisan would not be able to determine the metes and bounds of the claimed invention because it has not been clearly established what structures, other than γ-tocotrienol and paclitaxel, constitute the conjugate. As such, claim 15 is indefinite and lacks antecedent basis for the “paclitaxel-anchor moiety”.
2. Claim 30 is 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 30 recites the limitation "anchor moiety" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 30 further limits claim 13, which is silent about the “anchor moiety”. Likewise, parent claim 9 recites that the population of chemotherapeutic HDL mimetic micellular nanoparticles comprise: (c) a conjugate comprising γ-tocotrienol and paclitaxel. Although claim 30 recites that the anchor moiety is cholesterol or isomers (i.e., ß-, γ-, δ-) of tocotrienol or tocopherol; the claim is indefinite and lacks antecedent basis because an anchor moiety is a specific structural part of a molecule used to attach or tether the entire molecule to a surface, while a conjugate refers to the entire combined molecule itself.
Maintained/Modified Rejections in light of Amendments
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.
3. Claim 15 is 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 15 recites that the paclitaxel-anchor moiety is selected from a conjugate of Table 6. MPEP 2173.05(s) states that [w]here possible, claims are to be complete in themselves and that incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. In the instant case, claim 15 is indefinite because the contents of Table 6 is not incorporated in the claim. Table 6 depicts 14 paclitaxel-carbonate conjugates that can be incorporated as part of the claim limitation to further narrow the parent claim. Applicant may amend the claim by incorporating Table 6 as part of the claim instead of incorporating the contents by reference.
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.
4. Claims 9, 11-15 and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 10,532,105 B2. Date of Patent: Jan. 14, 2020 (herein after “Homan et al.”).
Homan claims a peptide amphiphile lipid micelle (PALM) comprising a peptide of claim 1, and a lipid component comprising sphingomyelin and one or more additional phospholipid (see column 83, claim 3). The peptide of claim 1, comprises an amino acid sequence of SEQ ID NO: 35 (see column 82, claim 2).
Homan’s SEQ ID NO: 35 is a 20 amino acid synthetic peptide wherein Xaa at position 7 and at position 14 corresponds to Aib. The peptide has the following sequence Asp-Val-Phe-Gln-Lys-Leu-Xaa-Glu-Leu-Phe-Asn-Gln-Leu-Xaa-Glu-Lys-Trp-Lys-Gln-Val (see column 61). As such, Homan’s SEQ ID NO: 35 is 100% identical to instant SEQ ID NO: 35.
Homan’s claim 3, is drawn to a peptide amphiphile lipid micelle (PALM) comprising a peptide of claim 1, and a lipid component comprising sphingomyelin and one or more additional phospholipids (see column 83). The PALM-cargo composition comprises at least one cargo molecule, wherein the molecule is a drug (see column 83, claims 5-9). Homan also claims that the cargo molecule is a conjugate having the formula (I) A-R-L-X, wherein A is an agent having a hydroxyl or an amine group R; L is a linker and X is an anchor moiety selected from the group consisting of cholesterol, α-tocotrienol, ß-tocotrienol, γ-tocotrienol, and δ-tocotrienol (see column 83, claim 8). As recited Homan’s claim 9, R is a hydroxyl group and the anchor moiety is covalently bonded to the agent by a carbonate ester bond (see column 83, claim 9). Furthermore, Homan claims that the PALM-cargo composition of claim 8, wherein R is an amine group and the anchor moiety is covalently bonded to the agent by a carbamate ester bond (see column 84, claim 10).The PALM-cargo composition of claim 8, wherein the agent is a drug (see column 84, claim 11); the drug is an anti-cancer drug (see column 84, claim 12); the anti-cancer drug is paclitaxel (see column 84, claim 13).
Homan discloses the micelle is composed of amphiphilic and hydrophobic molecules which aggregate in such a manner that the hydrophobic domains of molecules are shielded from the water and the hydrophilic constituents are at the micelle-water interface (see column 5, lines 45-49). Thereby corresponding to wherein the micellular nanoparticles in the population have a hydrophilic exterior surface and a hydrophobic core, as recited in instant claim 9.
Additionally, Homan’s Example 12, describes SR-BI interaction studies performed with BHK(SR-BI) cells. The incubations were performed with un-induced (control) or induced cells (i.e., SR-BI gene induced) and human HDL labeled with Dil (1,1'-dioctadecyl-3,3,3',3'tetramethylindocarbocyanine, see column 4, lines 56-57) was tested for comparison (see column 3, lines 45-46). Fig. 9, shows that the peptide with the highest pmol Dil/ug protein or peptide in induced cells was SEQ ID NO: 35 with 1.26+/- 6 pmol/ug/ml Dil uptake (see Fig. 9 and Table 6, column 35). Thereby corresponding to wherein the such hydrophilic exterior surface provides for the HDL mimetic structure, wherein the HDL mimetic structure is recognized by a SR-BI receptor, as recited in instant claim 9.
With respect to wherein the micellular nanoparticles in the population have an average particle diameter of from about 11.5 to about 14.0 nanometers, as measured by dynamic light scattering:
Homan discloses that the particle size is measured by DLS and is expressed as the hydrodynamic mean diameter (see column 14, lines 31-32). Homan adds that PALM are nanometer-size particles having a mean diameter of 30 nm or less, with a mean particle diameter from about 10nm to about 15nm (see column 14, lines 32-35, and lines 51-53). Per MPEP 2131.03 (I), "[W]hen, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art." Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985). Therefore, the instantly claimed particle diameter range of from about 11.5 to about 14.0 nanometers is anticipated by Homan’s disclosure of 30 nm or less and more specifically a mean particle diameter from about 10nm to about 15nm.
Furthermore, MPEP 2112.01 (II) states that "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. As such, since Homan’s peptide amphiphile lipid micelle (PALM) comprises SEQ ID NO: 35 which is 100% identical to instant SEQ ID NO: 35 and a cargo composition comprising γ-tocotrienol and paclitaxel, then, it must follow that Homan’s PALM have an average particle diameter of from about 11.5 to about 14.0 nanometers and that at least about 70% of the PALM are within plus/minus 3 nanometers of the average particle diameter.
Accordingly, Homan’s disclosure anticipates the instantly claimed invention as recited in claims 9, 11-15 and 30.
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.
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness
(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
5. Claims 9, 11-15 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over US 2011/0020242 A1 Pub. Date: Jan. 27, 2011 (herein after “Zheng et al.”), in view of US 10,532,105 B2 Date of Patent: Jan. 14, 2020 (herein after “Homan et al.”), Stjerndahl et al., J Surfact Deterg (2019) 22: 1139-1145 (herein after “Stjerndahl et al.”), and WO 00/59492 International Publication Date: Oct. 12, 2000 (herein after “Fariss et al.”)
Regarding claim 9, Zheng et al. teach pharmaceutical formulations comprising HPPS (High-Density Lipoprotein-like peptide phospholipid scaffold) nanoparticles and methods of making the HPPS nanoparticles (see Abstract). Zheng et al.’s HPPS nanoparticles contain anticancer agents, and such agents can be a chemotherapeutic agent (see pg. 4, para[0073]); thereby constituting a population of chemotherapeutic mimetic HDL mimetic micellular nanoparticles, as recited in instant claim 9.
Zheng et al. claim that the non-naturally occurring peptide-lipid nano scaffold comprises at least one peptide, the peptide comprising an amino acid sequence capable of forming at least one amphipathic α-helix (see pg. 21, claim 1). Zheng et al. teach examples of small amphipathic helix peptides, possessing many of the lipid binding properties of apoA-1 include 2F, an 18-amino acid peptide sequence with two phenylalanine amino acid residues (D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F) (see pg. 6, para[0100]). Thereby constituting an amphiphilic, alpha-helical peptide wherein said peptide forms an HDL mimetic structure on said nanoparticle, as recited in instant claim 9(a). Zheng et al. add that early studies showed that this sequence displayed strong lipid association and was able to form stable discoidal phospholipid particles (see pg. 6, para[0100]). Additionally, that subsequent studies went on to show that the incorporation of two additional F residues further enhanced the lipid associating properties of the peptide (see pg. 6, para[0100]).
Zheng et al. teach that the phospholipid of the peptide-lipid nano-scaffold is selected from phosphatidylcholine, POPC and EYPC (see pg. 21, claim 18), thereby constituting (b) one or both of sphingomyelin and phosphatidyl choline, and optionally additional lipid(s) or phospholipid(s), as recited in instant claim 9 (b).
Zheng et al.’s Figure 1 illustrates a HPPS nanoparticle that allow targeted delivery of active agents for the detection and treatment of cancers and other diseases(see pg. 3, para[0061]), where it can be seen that the particle size ranges from approximately 5-25 nm, the core loading comprises a drug (e.g., paclitaxel) (see Fig. 1). Zheng et al. further disclose that paclitaxel docosahexaenoic acid (DHA)-paclitaxel conjugates are examples of anti-cancer drugs (see pg. 8, para[0127]), thereby corresponding to a conjugate comprising paclitaxel, as recited in instant claim 9.
Zheng et al. add that cholesterol moieties may also be used to anchor other active agents within the core of the HPPS nanoparticles (see pg. 9, para[0137]). Such anchors may be covalently bound to active agents using synthetic methods known to those of skill in the art, and the anchors may also be covalently bound to the active agent via an ester linkage (see pg. 9, para[0137]), thereby constituting wherein the conjugate comprising paclitaxel is releasably attached to each other through a cleavable bond, as recited in instant claim 9(c).
Zheng et al. teach that the starting materials of the HPPS nanoparticles contain at least one lipid that is on, for example, the outer surface layer of the particle and that lipids useful in the HPPS nanoparticles include, but are not limited to, amphipathic lipids. (see pg. 5, para[0091]). Additionally, that drug/probe sequestration in the lipid core space provides protection from serum enzyme and water (see pg. 5, para[0089]), thereby constituting wherein the micellular nanoparticles of the population have a hydrophobic core, as recited in instant claim 9. As such, if the HPPS nanoparticle includes amphipathic lipids, and if the lipid core provides protection form serum enzyme and water, it must follow that the nanoparticles have a hydrophilic exterior; thereby constituting wherein the micellular nanoparticles in the population have a hydrophilic exterior, as recited in instant claim 9.
Zheng et al. disclose Fig. 21, which demonstrates the specificity of HPPS for the SR-BI receptor (see pg. 18, para[0246]). The specificity was demonstrated by incubating SR-BI positive and SR-BI negative cells with (DiR-BOA)HPPS particles for 3 hours; confocal images show strong uptake of (DiR-BOA)HPPS in SR-BI positive cells (ldlA(mSR-BI)) but not in SR-BI negative cells (LDLA7) (see pg. 18, para[0246]). Thereby constituting to wherein the HDL mimetic structure is recognized by a SR-BI receptor, as recited in instant claim 9.
Zheng et al. also teach that the non-naturally occurring HPPS nanoparticles are from 10 nm to 15 nm in diameter (see pg. 5, para[0090]); thereby constituting wherein the micellular nanoparticles in the population have an average particle diameter of from about 11.5 to about 14.0 nanometers, as recited in instant claim 9. Additionally, MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses by the prior art" a prima facie case of obviousness exists. Therefore, the claimed particle diameter range would have been obvious to one of ordinary skill in the art since the prior art range (i.e., 10nm to 15 nm) lies within the claimed 11.5 nm to about 14.0 nm.
Zheng et al. teach Table 4, which indicates the proportion of the population of nanoparticles that have the indicated size (see pg. 15, Table 4). Table 4, displays the mean size, percent composition, where it can be appreciated that 99% of the particles had a mean size between 10.9nm and 13.7nm (see Table 4 at pg. 9); thereby constituting wherein at least 70% of said C-m-HDLs in said population are within plus/minus 3 nm of the average particle diameter, as recited in instant claim 9.
Additionally, the percentage of the C-m-HDLs nanoparticles in the population that are within plus/minus 3 nm of the average particle diameter is clearly a result specific 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. It would have been customary for an artisan of ordinary skill to determine the optimal average particle diameter needed to achieve the desired results. Thus, an ordinary skilled artisan would have been motivated to modify the particle components (e.g., peptide, payload stability, conjugate characteristics, etc.), because an ordinary skilled artisan would have been able to utilize the teachings of Zheng et al. to obtain various size and percent composition parameters with a reasonable expectation of success. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of the percentage of C-m-HDLs in the population that are within plus/minus 3 nanometers of the average particle diameter would have been obvious at the time of Applicant's invention. Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, because the combined teachings of the prior art are fairly suggestive of the claimed invention.
However, Zheng et al. do not expressly teach SEQ ID NO: 35, nor a conjugate comprising γ-tocotrienol.
Homan et al. teach peptide amphiphile lipid micelles (PALM), process for making them and optionally comprising a cargo molecule (see abstract); as well as compound conjugates and methods of preparing compound conjugates suitable for use with PALM) (see pg. 2, lines 17-59. Homan et al.’s Table 2 depicts particular peptides of the invention, such as peptide sequence DVFQKL{AIB}ELFNQL{AIB}EKWKQV identified with SEQ ID NO: 35 (see column 9, line 35). Homan et al.’s SEQ ID NO: 35 is 100% identical to instant SEQ ID NO: 35 (i.e., Applicant’s elected species). Homan et al. also teach that the amphiphilic peptides are able to adopt an alpha helical conformation in which the helix has opposing polar and non-polar faces oriented along the long axis of the helix (see column 5, lines 66-67 and column 6, lines 1-4). Thereby constituting (a) an amphiphilic, alpha-helical peptide that comprises an amino acid sequence of SEQ ID NO: 35, as recited in instant claim 9.
Homan et al. teach Fig. 9, which depicts PALM prepared with various peptides as indicated, and containing Dil, were incubated with BHK (SR-BI); the incubations were performed with un-induced (control) or induced cells (i.e., SR-BI gene induced) and human HDL labeled with Dil (1,1'-dioctadecyl-3,3,3',3'tetramethylindocarbocyanine, see column 4, lines 56-57) was tested for comparison (see column 3, lines 45-46). Fig. 9, shows that the peptide with the highest pmol Dil/ug protein or peptide in induced cells was SEQ ID NO: 35 with 1.26+/- 6 pmol/ug/ml Dil uptake (see Fig. 9 and Table 6, column 35). As such, the teachings of Zheng et al. when combined with the teachings of Homan et al. are suggestive of the claim limitations as recited in claim 9 (a) wherein an amphiphilic, alpha-helical peptide comprise an amino acid sequence of SEQ ID NO: 35.
Homan et al.’s Table 5, provides PALM-cargo compositions of formula A-R-L-X wherein the first entry is Paclitaxel-γ-tocotrienol (see columns 23 and 24). It is also noticed that the second entry in Table 5 discloses paclitaxel-δ-tocotrienol (i.e., moiety No. 79 from instant Table 6) and the fifth entry in Table 5 discloses Paclitaxel cholesterol (i.e., moiety No. 71 from instant Table 6). Thereby constituting (c) a conjugate comprising γ-tocotrienol and paclitaxel, as recited in instant claim 9.
From the teachings of the references, the Examiner recognizes that it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zheng et al.’s invention by substitute the 2F apoA-1 sequence with Homan et al.’s SEQ ID NO: 35 and the DHA-Paclitaxel conjugate with Homan et al.’s paclitaxel-γ-tocotrienol conjugate in order to arrive at the instantly claimed invention.
One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because Homan et al.’s SEQ ID NO: 35 is 100% identical to instant SEQ ID NO: 35; and because the peptide amphiphile lipid micelles (i.e., PALM) prepared with SEQ ID NO: 35 exhibited the highest Dil uptake by SR-BI positive cells; and because Homan’s cargo comprises Paclitaxel-γ-tocotrienol which is a suitable conjugate for use with PALM.
One of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success given that Homan et al.’s SEQ ID NO:35 was known to be used in compositions for delivering cargo to cells wherein the cargo comprises paclitaxel. Given that Zheng et al.’s HDL-like peptide-phospholipid scaffold (HPPS) nanoparticles comprises at least one peptide capable of forming at least one amphipathic α-helix; and given that the amphipathic helix peptides, possessing many of the lipid binding properties of apoA-1 include two phenylalanine amino acid residues (i.e., 2F) which display strong lipid association and are able to form stable discoidal phospholipid particles.
Therefore, substituting Zheng et al.’s apoA-1 2F peptide with Homan et al.’s SEQ ID NO: 35 and Zheng’s DHA-paclitaxel conjugate with Homan’s paclitaxel-γ-tocotrienol conjugate would support the instantly claimed invention by constituting some teaching, suggestion or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention; and/or the simple substitution of one known element for another to obtain predictable results; and/or use of known technique to improve similar devices (methods, or products) in the same way, pursuant to KSR.
Regarding claim 11, as previously mentioned, Zheng et al. teach that cholesterol moieties may be covalently bound to active agents using synthetic methods known to those of skill in the art, and the anchors may also be covalently bound to the active agent via an ester linkage (see pg. 9, para[0137]); thereby constituting wherein the cleavable bond is an ester, as recited in instant claim 11.
Regarding claim 12, Zheng et al. teach that suitable anchors for active agents include oleate and unsaturated cholesterol ester moieties (see pg. 9, para[0137]). Such anchors may be covalently bound to active agents using synthetic methods known to those of skill in the art (see pg. 9, para[0137]). The anchors may be covalently bound to the active agent via an ester linkage (see pg. 9, para[0137]). However, Zheng et al. do not expressly teach wherein the releasable bond is a carbonate bond as, recited in instant claim 12.
Homan et al. teach that the PALM-cargo molecule complex is a compound conjugate of formula (I) i.e., A-R-L-X (see column 15, lines 31-35); wherein A is an agent having an hydroxy or amine group and wherein R is a hydroxy group or amine group of the agent, and the anchor moiety is covalently bonded to agent by a carbonate ester bond (see column 16, lines 6-7); thereby constituting wherein the cleavable bond is a carbonate bond. Additionally, Homan et al. teach that the agent is an anticancer drug covalently bonded to the anchor by a carbonate ester bond (see column 16, lines 27-29); for instance the cargo molecule is paclitaxel 2'-cholesteryl carbonate (see column 16, lines 43-45).
Stjerndahl et al. are in the field of cleavable surfactants and teach a comparison between ester, amide and carbonate as the weak bond (see pg. 1139, Title). In particular, Stjerndahl et al. compare the physical-chemical properties and degradation characteristics of three types of surfactants: amphiphiles with either amide, carbonate, or ester (“normal ester”) as hydrolysable linkage between the polar headgroup and the hydrophobic tail (see pg. 1140, right column, paragraph 3). Stjerndahl et al. teach Table 1, which depicts the physical-chemical properties as well of half-lives of the cleavable surfactants; where it can be appreciated that the critical micelle concentration (CMC) and cloud point (CP) values of the carbonate surfactant are the lowest and the carbonate bond is more unipolar than the ester bond and it is also more stable to alkaline hydrolysis than an ester bond (see pg. 1141, right column, paragraph 1). Stjerndahl et al. conclude that surface-active molecules with a carbonate bond between the hydrophobic tail and the polar headgroup are of interest as cleavable surfactants, particularly when one wants to avoid acidic degradation products (see pg. 1145, left column, paragraph 2). Judging from values of the CMC and CP, a carbonate linkage is somewhat less hydrophilic than an ester bond and it is slightly more stable to alkaline hydrolysis than an ester bond (see pg. 1145, left column, paragraph 2).
From the teachings of the references, the Examiner recognizes that it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the ester linkage between the lipid anchors and the active agent of Zheng et al. with the carbonate ester bond of Homan et al. in order to arrive at the claimed population of C-m-HDLs wherein the cleavable bond is a carbonate bond. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because the physical and chemical properties of cleavable surfactants with carbonate or ester hydrolysable linkage between the polar headgroup and the hydrophobic tail were known; because it was also known that the carbonate bond is more unipolar than the ester bond and it is also more stable to alkaline hydrolysis than an ester bond as taught by Stjerndahl et al. One of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success given that the PALM-cargo molecule complex is a conjugate of an agent (i.e., paclitaxel) and an anchor moiety covalently bonded by a carbonate ester bond as taught by Homan et al. Therefore, substituting Zheng et al.’s ester linkage between the lipid anchors and the active agent with Homan et al.’s carbonate ester bond would support a population of C-m-HDLs wherein the cleavable bond is a carbonate bond by constituting some teaching, suggestion or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Regarding claim 13, as previously mentioned, Zheng et al. teach that the non-naturally occurring HPPS nanoparticles are from 10 nm to 15 nm in diameter (see pg. 5, para[0090]); thereby constituting wherein an average particle diameter of from about 12 to about 13.5 nanometers, as recited in instant claim 13. Additionally, MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses by the prior art" a prima facie case of obviousness exists. Therefore, the claimed particle diameter range would have been obvious to one of ordinary skill in the art since the prior art range (i.e., 10nm to 15 nm) lies within the claimed 12 nm to about 13.5 nm.
Regarding claim 14, as previously mentioned, Zheng’s Table 4, displays the mean size, percent composition, where it can be appreciated that 99% of the particles had a mean size between 10.9nm and 13.7nm (see Table 4 at pg. 9); thereby constituting wherein at least 70% of said C-m-HDLs are within plus/minus 2 nm of the average particle diameter, as recited in instant claim 14.
Regarding claims 15 and 30, Zheng et al. teach that at least one active agent is bound to at least one lipid anchor (see pg. 21, claim 25). Additionally, Zheng et al. teach docosahexaenoic acid (DHA)-paclitaxel conjugates (see pg. 9, para[0127]). However, Zheng et al. do not expressly teach wherein the paclitaxel-anchor moiety is moiety No. 78 , i.e., Paclitaxel-γ-tocotrienol conjugate with a cleavable carbonate bond (i.e., Applicant’s elected species).
Homan et al. teach that in a compound conjugate of formula (I) i.e., A-R-L-X, the anchor moiety is γ-tocotrienol (see column 16, lines 20-21). Homan et al.’s Table 5, provides PALM-cargo compositions of formula A-R-L-X wherein the first entry is Paclitaxel-γ-tocotrienol (see columns 23 and 24). It is also noticed that the second entry in Table 5 discloses paclitaxel-δ-tocotrienol (i.e., moiety No. 79 from instant Table 6) and the fifth entry in Table 5 discloses Paclitaxel cholesterol (i.e., moiety No. 71 from instant Table 6).
Fariss et al. teach methods for the use of derivatives of vitamin E (tocopherol and tocotrienol), cholesterol, taxol and betulinic acid as antitumor agents for the treatment of and prevention of cancers (see Abstract). Fariss et al. add that the derivatives may be used alone or in combination with one another, or with other antitumor agents (see pg. 1, summary). Vitamin E is a generic term that includes, in nature, eight substances d-α-, d-ß-, d-γ-, d-δ-tocopherol and d-α-, d-ß-, d-γ-, d-δ-tocotrienol (see pg. 7, paragraph 3). Fariss et al. investigated whether the combination of several of these tocopherol and tocotrienol succinate esters would have antitumor activity (see pg. 7, paragraph 3). To accomplish this, a succinate ester of tocotrienol rich fraction (TRF) was prepared (TRF-S) in the form of both a free acid and a tris salt (see pg. 7, paragraph 3). TRF-S is a mixture of vitamin E compounds containing the succinate ester of d-α-tocopherol (28%) and d-α- tocopherol (35%), d-γ-tocotrienol (22%), and d-δ-tocotrienol (16%) (see pg. 7, paragraph 3). The presence of the succinate ester of each of these vitamin E derivatives in the TRF-S preparation was confirmed by HPLC analysis using base hydrolysis (see pg. 7, paragraph 3). The findings indicate that a mixture of tocopherol and tocotrienol esters (as, for example, TRF-S-tris or TRF-S free acid) are potent antitumor agents (see pg. 7, paragraph 3).
From the teachings of the references, the Examiner recognizes that it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the lipid anchor Zheng et al. with Homan et al.’s γ-tocotrienol anchor moiety in order to arrive at a population of C-m-HDLs comprising a paclitaxel-anchor moiety wherein the moiety is γ-tocotrienol. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because γ-tocotrienol as well as other vitamin E derivatives such as α-, ß-, -δ-tocotrienol and α-, ß-, γ-, δ-tocopherol have potent antitumor activity as taught by Fariss et al. One of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success given that it was known that γ-tocotrienol was used as an anchor moiety was part a cargo composition comprising paclitaxel in the peptide amphiphile lipid micelles of Homan et al. Therefore, substituting Zheng et al.’s lipid anchor with Homan et al.’s γ-tocotrienol would support an amphiphilic, alpha-helical peptide wherein the paclitaxel-anchor moiety is Paclitaxel-γ-tocotrienol conjugate with a cleavable carbonate bond (i.e., moiety No. 78) by constituting some teaching, suggestion or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the above claims would have been obvious to one of ordinary skill in the art within the meaning of 35 USC 103. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references discussed above.
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.
6. Claims 9, 11-15 and 30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-9, 11-15, 17, 19 and 21 of U.S. Patent No. 10,532,105 B2 (Application number 15/743,098).
Regarding instant claims 1-2, 9, 11-12, 15-16 and 20; U.S. Patent No. 10,532,105 B2 claims:
a peptide amphiphile lipid micelle (PALM) comprising a peptide and a lipid component comprising sphingomyelin and one or more additional phospholipid, wherein the peptide comprises the amino acid sequence X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X5-X6-X17-X8-X19-X20 wherein: X1 is the amino acid D; X2 and X20 are each the amino acid V; X3, X6, X10 and X13 are each an amino acid independently selected from the group consisting of L and F; X4, X12 and X19 are each the amino acid Q; X5 is the amino acid A or Aib; X7, X16 and X18 are each the amino acid K; X8 and X15 are each the amino acid E; X9 and X14 are each an amino acid independently selected from the group consisting of A, L, F and Aib; X11 is an amino acid selected from the group consisting of A, Aib and N; and X17 is an amino acid selected from the group consisting of W, F and L (see ‘105, claims 1-3).
‘105 also claims that the PALM comprises one or more additional phospholipid selected from the group consisting of phosphatidylcholine (see claim 4); and a cargo composition comprising at least one cargo molecule wherein the molecule is an imaging agent or a drug (see ‘105, claim 5); wherein the
at least one cargo molecule is a conjugate having the formula (I) A-R-L-X, wherein A is an agent having a hydroxyl or an amine group R; L is a linker and X is an anchor moiety selected from the group consisting of cholesterol, α-tocotrienol, ß-tocotrienol, γ-tocotrienol, and δ-tocotrienol (see ‘105, claim 8). The R is a hydroxyl group and the anchor moiety is covalently bonded to the agent by a carbonate ester bond (see ‘105, claim 9).
Claims 11-15, 17, 19 and 21 of U.S. Patent No. 10,532,105 B2 recite that agent is a drug; the drug is an anti-cancer drug; the anti-cancer drug is paclitaxel; X (i.e., an anchor moiety) is ß-tocotrienol or δ-tocotrienol, and that the peptide is selected from the group consisting of SEQ ID NOs: 25, 28, 34 and 35.
Although the claims at issue are not identical, they are not patentably distinct from each other.
7. Claims 9, 11-15 and 30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-14, 17 and 21 of copending Application No. 19/204,092 (reference application), claim listing filed May 9, 2025, PG Pub US20250345453A1.
Regarding instant claim 9, copending Application ‘092 claims:
A population of C-m-HDLs comprising: (a) an amphiphilic, alpha-helical peptide that comprises an amino acid sequence of any one of SEQ ID NO:25, SEQ ID NO:28, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO. 36, or combinations thereof wherein said peptide forms an HDL mimetic structure on said nanoparticle; (b) one or both of sphingomyelin and phosphatidyl choline, and optionally additional lipid(s) or phospholipid(s); (c) a conjugate comprising an anchor moiety molecule and a chemotherapeutic agent that is releasably attached to each other through a cleavable bond; and wherein the micellular nanoparticles in the population have a hydrophilic exterior surface and a hydrophobic core; and further wherein the micellular nanoparticles in the population have an average particle diameter of from about 11.5 to about 14.0 nanometers, as measured by dynamic light scattering (see copending App. ‘092, claim 9).
The population of C-m-HDLs of claim 9, wherein at least about 70% of said C-m- HDLs in said population are within plus/minus about 3 nanometers of the average particle diameter (see copending App. ‘092, claim 10).
A population of C-m-HDLs which population comprises: a) an amphiphilic, alpha-helical peptide that comprises an amino acid sequence of any one of SEQ ID NO:25, SEQ ID NO:28, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO. 36, or combinations thereof wherein said peptide forms an HDL mimetic structure on said C-m- HDLs;(b) one or both of sphingomyelin and phosphatidyl choline, and optionally additional lipid(s) or phospholipid(s);(c) a chemotherapeutic-lipid conjugate selected from conjugates in Tables 1-5 (see copending App. ‘092, claim 17).
The population of claim 17, wherein said amphiphilic, alpha-helical peptide has an amino acid sequence as provided by SEQ ID NO: 35 (see copending App. ‘092, claim 21).
Regarding instant claims 11-12, copending Application ‘092 claims:
The population of C-m-HDLs of claim 9, wherein the releasable bond is selected from an ester, a thioester, a carbonate, a thiocarbonate, a carbamate, or a thiocarbamate bond (see copending App. ‘092, claim 11). The population of C-m-HDLs of claim 9, wherein the releasable bond is a carbonate bond (see copending App. ‘092, claim 12).
Regarding instant claims 13, copending Application ‘092 claims:
The population of C-m-HDLs of claim 9, wherein said C-m-HDLs in the population have an average particle diameter of from about 12 to about 13.5 nanometers; and wherein said C-m-HDLs in the population have an average particle diameter of from about 12 to about 13.5 nanometers (see ‘092, claims 3 and 13).
Regarding instant claim 14, copending Application ‘092 claims:
The population of C-m-HDLs of claim 13, wherein at least about 70% of said C- m-HDLs in said population are within plus/minus about 2 nanometers of the average particle diameter (see copending App. ‘092 claim 14).
Although the claims at issue are not identical, they are not patentably distinct from each other. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Additionally, ‘092 claims are a species of the instantly claimed invention.
8. Claims 9, 11-15 and 30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8-10, 17-19 and 23-26 of copending Application No. 18/041,289 (reference application) PG Pub US20230265123A1. See the claim listing filed February 10, 2023 version 1/2.
Regarding instant claims 9 and 11-14; copending Application ‘289 claims:
a peptide comprising an amino acid sequence: X1- X2 -X3- X4 -X5 -X6 -X7 - X8 -X9 -X10 -X11 -X12 -X13 -X14 -X15 -X16 -X17 -X18- X19 -X20, wherein: X1 is D; X2 is V, Aib, Amy, or Aml; X3 and X10 are each F; X4 and X19 are each Q; X5, X16, and X18 are each K; X6, X9, and X13 are each L; X7 and X14 are each independently selected from the group consisting of Aib, Amy, Aml, Amp, Amt; X8 and X15 are each E; X11 and X12 are each independently selected from the group consisting of Q and N; X17 is W; and X20 is V, (SEQ ID NO: 12) wherein the peptide is optionally acylated at the N-terminus, amidated at the C-terminus, or both acylated at the N-terminus and amidated at the C-terminus and the peptide is from 20 to 24 amino acids in length (see ‘289, claim 1).
Claim 8 in copending Application ‘289 is drawn to a peptide-amphiphile lipid micelle (PALM) comprising a peptide according to claim 1, and a lipid component comprising sphingomyelin and one or more additional phospholipids. Wherein the one or more additional phospholipid is selected from the group consisting of phosphatidylcholine, polyethylene glycol-phosphatidylethanolamine (PEG-PE), phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, phosphatidylinositol, cardiolipin, or any combination thereof (see ‘289, claim 9); wherein the one or more additional phospholipid comprises a phosphatidylcholine (see ‘289, claim 10).
Claim 17 in ‘289 is drawn to A PALM-cargo composition comprising the PALM according to any claims8, and at least one cargo molecule. Wherein the at least one cargo molecule is a compound conjugate having the formula (I): A-R-L-X (formula I) wherein A is an agent having a hydroxyl or an amine group; R is the hydroxyl group or the amine group of the agent; L is a linker; and X is an anchor moiety (see ‘289, claim 18); wherein the anchor moiety X is cholesterol, α-tocotrienol, ß-tocotrienol, γ-tocotrienol, and δ-tocotrienol, cholecalciferol, or ergocalciferol (see ‘289, claim 19).
‘289 also claims that the PALM-cargo composition according to claim 18 is a chemotherapeutic agent (see ‘289, claim 23); wherein the chemotherapeutic agent is selected from the group consisting of adenosine, AZD2811, bortezomib, 10-hydroxy camptothecin, 7-ethyl-10-hydroxycamptothecin, daunorubicin, docetaxel, doxorubicin, eribulin, gemcitabine, ixabepilone, mertansine, miriplatin, misonidazole, paclitaxel, topotecan, tubulysin A, vincristine, vinblastine, vinorelbine, and combinations thereof (see ‘289, claim 24); and wherein the chemotherapeutic agent is 10-hydroxy camptothecin, daunorubicin, doxorubicin, gemcitabine, topotecan, paclitaxel, or docetaxel (see ‘289, claim 25).
Although the claims at issue are not identical, they are not patentably distinct from each other. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant’s arguments filed 07/01/2026, pertaining to the 35 U.S.C 102(a)(1) over US 10,532,105 B2 Date of Patent: Jan. 14, 2020 (herein after “Homan”), have been fully considered but they are not persuasive.
In response to applicant's argument that Homan’s disclosure fails to show certain features of the invention (see Remarks, filed 07/01/2026, pg. 12, paragraph 2). It is noted that the features upon which applicant relies (i.e., use of a disaccharide during the formation of the nanoparticles, and that the amount of disaccharide is limited to a specific range) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Furthermore, the examined claims are drawn to a product and not a method of making or product by process, therefore Applicant’s arguments and provided support (i.e., Examples 5 and 10 of instant specification) are found unpersuasive and irrelevant.
Applicant’s arguments filed 07/01/2026, pertaining to the 35 U.S.C 103 rejection over US 2011/0020242 A1 Pub. Date: Jan. 27, 2011 (herein after “Zheng et al.”), in view of US 10,532,105 B2 Date of Patent: Jan. 14, 2020 (herein after “Homan et al.”), Stjerndahl et al., J Surfact Deterg (2019) 22: 1139-1145 (herein after “Stjerndahl et al.”), and WO 00/59492 International Publication Date: Oct. 12, 2000 (herein after “Fariss et al.”); have been fully considered but they are not persuasive.
In response to Applicant’s assertions that the newly presented claims recite features not taught in the foregoing references, such as the recitation of “at least about 70% of said chemotherapeutic HDL mimetic micellular nanoparticles in said population are within plus/minus 3 nanometers of the average particle diameter” (see Remarks, filed 07/01/2026, pg. 14, first paragraph). This argument has been fully considered but it is not persuasive.
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, Zheng et al., as best understood, teaches Table 4, which indicates the proportion of the population of nanoparticles that have the indicated size (see pg. 15, Table 4). More specifically, Zheng’s Table 4, displays the mean size, percent composition, where it can be appreciated that 99% of the particles had a mean size between 10.9nm and 13.7nm (see Table 4 at pg. 9). Additionally, the percentage of C-m-HDLs that are within plus/minus 3 nanometers of the average particle diameter is clearly a result specific parameter that a person of ordinary skill in the art would routinely optimize. Therefore, Zheng’s teachings read on wherein at least about 70% of said C-m-HDLs in said population are within plus/minus 3 nm of the average particle diameter, as recited in instant claim 9.
MPEP 2145 (IV) states that [o]ne cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). This is because "[T]he test for obviousness is what the combined teachings of the references would have suggested to [a PHOSITA]." In re Mouttet, 686 F.3d 1322, 1333, 103 USPQ2d 1219, 1226 (Fed. Cir. 2012).
This is pertinent because Applicant’s rebuttal arguments are mainly focused on the teachings of Zheng et al. Therefore, Applicants are respectfully reminded 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). As discussed in the 35 U.S.C 103 rejection above, motivation was provided to modify the primary reference (i.e., Zheng et al.) with features found in a secondary reference (i.e., Homan et al.) in order to arrive at the claimed invention. Therefore, the combination of references read on the instantly claimed invention and thus an ordinary skilled artisan would have had a reasonable expectation of success to arrive at the instant invention.
In response to Applicant’s argument, i.e., as shown in the examples of this application, the diameters of nanoparticles prepared as described therein using an alpha helical peptide with 20 amino acids have a diameter of 17 nanometers when prepared in the absence of a disaccharide. It is only when a disaccharide is incorporated into the formation of the nanoparticles that the diameter is reduced to around 12 nm. So, the evidence provided establishes that the length of the peptide impacts the size and, hence, the diameter of the nanoparticles generated therefrom (see Remarks, filed 07/01/2026, pg. 15, paragraph 1); has been fully considered but it is not persuasive.
It is noted that the features upon which applicant relies (i.e., incorporation of a disaccharide and particle diameter of 12nm) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The scope of instant claim 9 encompasses a population of chemotherapeutic HDL mimetic micellular nanoparticles having an average particle diameter of from about 11.5 to about 14.0 nanometers, wherein at least 70% of the particles in the population are within plus/minus 3 nanometers of the average particle diameter. Therefore, the scope of claim 9 and dependent claims do not correlate a product by process wherein a disaccharide is included in order to achieve a reduced particle diameter to around 12 nm.
Moreover, the fact that the inventor has recognized that the incorporation of a disaccharide into the formation of the nanoparticles reduces the particle diameter from 17 nanometers to around 12 nm, cannot be the basis for patentability when the examined claims are drawn to a product. Even if the scope of the instant claim encompassed the incorporation of a disaccharide into the formation of the nanoparticles reduces the particle diameter from 17 nanometers to around 12 nm; and assuming arguendo that the cited art does not expressly suggest incorporating a disaccharide in order to reduce particle diameter to around 12nm. Since the particle size and percent distribution are clearly result specific parameters that a person of ordinary skill in the art would routinely optimize; it would have been customary for an artisan of ordinary skill to determine the optimal average particle diameter needed to achieve the desired C-m-HDLs.
Applicant’s assertions that the length of the peptide impacts the size and, hence the diameter of the nanoparticles (see Remarks, filed 07/01/2026, pg. 15, first paragraph), are not only found unpersuasive but also contradictory to the instant claims. Such contradiction is rooted in the fact that all the peptides of the instant invention are 20 amino acids in length, in particular SEQ ID NO: 35. Following Applicant’s logic, Zheng’s nanoparticles should be relatively smaller and have an average particle diameter that falls out of the instantly claimed range, since Zheng’s peptide is only 18 amino acids in length. And so, incorporation of a disaccharide to reduce particle diameter from 17nm to 12 nm would result unnecessary, when the peptide is 20 amino acids in length (e.g., instant SEQ ID NO: 35).
Accordingly, the 35 U.S.C 103 rejection to claims 9, 11-15 and 30 has been maintained.
In response to Applicant’s argument, the obviousness double patenting rejections are predicated on the same logic as the obviousness rejection above and for the same reasons is traversed (see Remarks, filed 07/01/2026, pg. 15, last paragraph), have been fully considered but are not persuasive.
Applicant has not identified a meaningful distinction that would render the presently claimed subject matter patentably distinct from the claims in U.S. Patent No. 10,532,105 B2; copending Application 18/041,289; and copending Application 19/204,092.
Accordingly the NSDP rejections have been maintained.
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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/CLAUDIA ESPINOSA/ Patent Examiner, Art Unit 1654
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654
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