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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 1, 2025 has been entered.
Applicants' arguments, filed May 1, 2025, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application. The arguments regarding the previous new matter rejection have been considered but as detailed below, the claims as presently amended still contain subject matter that is not supported by the disclosure as originally filed. In view of the claim amendments and new prior art rejections set forth below, the arguments regarding the previously applied prior art are moot.
Claim Rejections - 35 USC § 112 – New Matter
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 70 – 72, 75, 78, 94 and 95 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. This is a new matter rejection.
Claim 70, from which all other claims depend, requires the presence of a high molecular weight alcohol having 10 to 22 carbon atoms and the full scope of this genus of claimed of alcohols is not supported by the disclosure as filed. The phrases “long chain alcohols” or “high molecular weight alcohols” are used throughout the specification but are not specifically defined. The 4 specific alcohols recited in claim 88 are specifically disclosed – decyl (10 carbons), stearyl (18 carbons), cetyl (16 carbons) and behenyl (22 carbons). In addition to having an even number of carbon atoms, all of these alcohols comprise linear alkyl chains. The 4 species are not sufficient species within the claimed genus to support the broad genus being claimed. The independent claim not only includes high molecular weight alcohols with odd numbers of carbon atoms but also branched alkyl chains. There is no indication that the use of such non-linear and/or odd number of carbon atoms alcohols was contemplated for inclusion in the claimed lamellar vesicles in the disclosure as originally filed.
The dependent claims fall therewith.
If Applicant is in disagreement with the Examiner regarding support for the amended claim, Applicant is respectfully requested to point to additional locations wherein support may be found for the instant invention and/or explain how the specific materials disclosed are sufficient species to support the entire genus being claimed.
Claim 72 is 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. This is a new matter rejection.
While ¶ [0055] of the PGPub of the instant application provides explicit support for the lower endpoint of the claimed range, the only disclosure of the upper range endpoint of 4.5 is in Table 2 for one specific formulation and the data appear to have been collected at 22°C (¶ [0070] of the PGPub of the instant application) and the total amount of vesicle forming components is 5% w/w while lies out the range recited in claim 70 with recites 3% w/w or less of vesicle forming components. There is no indication that values for Kapp above 3.0 such as 4.5 over the full temperate range of 19 – 25°C for any lamellar vesicle system as in claim 70 was contemplated in the disclosure as originally filed.
If Applicant is in disagreement with the Examiner regarding support for the amended claim, Applicant is respectfully requested to point to additional locations wherein support may be found for the instant invention and/or explain how the specific materials disclosed are sufficient species to support the full scope of this claim.
Claim 95 is 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. This is a new matter rejection.
This claim recites a range of values for the diffusion restricted water which is not specifically disclosed in the specification as originally filed. As set forth in previous new matter rejections related to this claimed parameter, the parameter P2 used for fitting obtained data with a biexponential curve, along with two other parameters (see ¶ [0070] of the PGPub of the instant application), might correspond to at least this general claim limitation. Table 2 recites values of 13% and 68% for P2, but these are not only derived from the fitting of experimental data and are both with CA-BTAC formulations with varying concentrations. The 68% P2 value is for a composition with 5 wt% as the concentration, which exceeds the upper limit recited in claim 70, from which claim 95 depends, of 3% or less by weight of vesicle forming components. Therefore, that P2 is in fact the claimed parameter of “diffusion restricted water” and that values ranging from 13% to 68% for any formulation as in claim 70 with any ionic surfactant, any 10 – 22 carbon atom alcohol and less than 3% by weight vesicle forming components is not sufficiently supported by the one parameter in one table for one formulation with cetearyl alcohol and behentrimonium chloride.
If Applicant is in disagreement with the Examiner regarding support for the amended claim, Applicant is respectfully requested to point to additional locations wherein support may be found for the instant invention and/or explain how the specific materials disclosed are sufficient species to support the full scope of this claim and that P2 for this specific fitting procedure corresponds exactly in scope to the claim language of “diffusion restricted water”.
In the arguments, Applicants refer to an abstract by Swanson et al. that the Examiner determined was cited on the IDS filed June 2, 2022. That document does not describe the biexponential used and states “P2 restricted fraction” which is not the same as the language used in this claim and the evidence of record does not make it clear that the biexponential of the instant application and that referenced in Swanson et al. are the same and the only manner in which “diffusion restricted water” can be mentioned since claim 95 encompasses all possible methods of determining the amount of diffusion restricted water. Therefore these arguments are unpersuasive.
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.
Claim(s) 70 – 72, 74, 75, 78, 88, 93 and 95 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nakarapanich et al. (Colloid Polym Sci, 2001).
Nakarapanich et al. discloses systems of either cetyltrimethylammonium chloride (CTAC) or behenyltrimethylammonium chloride (BTAC) mixed with fatty alcohol (FA; whole document, e.g., abstract) with FA being a homologous admixture of cetyl and stearyl alcohols as in cetostearyl alcohol (p 671, col 1, ¶ 2 and p 672, col 2, ¶ 4). Figures 4A and 8A show images from a composition of 1.0% w/w CTAC and 2.0% w/w FA (3.0% w/w total vesicle forming components, ratio alcohol to surfactant 2:1) that form vesicular structures (¶ bridging cols 1 and 2 on p 674). Figure 4B comprises 1.0% w/w BTAC and 2.0% w/w FA (3.0% w/w total vesicle forming components, ratio alcohol to surfactant 2:1). The single particle shown in each figure panel is at least 500 nm in diameter given the scale bar of 50 µm for each set of figures. The material shown in Fig. 8B also contains 0.5% w/w of the water soluble polymer HEC (hydroxy ethyl cellulose) and reduces the size of the isolated lamellar and vesicular aggregates (p 676, col 1, ¶ 3) although the diameter remains at least 500 nm (0.5 µm).
Properties such as the diffusion constant Dapp, kurtosis constant Kapp and percent diffusion restricted water are not disclosed. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). “As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” MPEP 2113 Here compositions meeting the physical and structural limitations are disclosed by the prior art but the diffusion constant Dapp, kurtosis constant Kapp and percent diffusion restricted water were not measured but are determined by the structure of the composition. Absent evidence of record that the materials of Nakarapanich et al. do not possess these properties, the rejection of the claims requiring such properties will be maintained.
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.
Claim(s) 70 – 72, 74, 75, 78, 88 and 93 - 95 are rejected under 35 U.S.C. 103 as being unpatentable over Nakarapanich et al. (Colloid Polym Sci, 2001) in view of Csempesz et al. (Coll Interf Sci Series, 2007).
In addition to the teachings of Nakarapanich et al. discussed above, Nakarapanich et al. discloses that the rheological and optical properties of ternary mixtures of water, an FA and an anionic surfactant have been well-investigated but systems with those containing a cationic surfactant are less understood (p 672, col 1, ¶ 3). Lamellar and vesicular aggregates form for the CTAC/FA emulsions at low FA contents (NFA/NCTAC < 4) through fusion of small vesicles and lamellar bilayers (¶ bridging cols 1 and 2 on p 674). The longer hydrocarbon tail of BTAC leads to a lesser degree of interaction with an FA and produced multilamellar vesicle structures rather than lamellar and vesicular aggregates in BTAC/FA compositions (¶ bridging cols 1 and 2 on p 674). A high FA content of 6% w/w results in a nearly continuous network-like or sunflower-like structure for the CTAC/FA and BTAC/FA systems respectively (p 677, col 1, ¶ 1). The presence of the HEC delays the aging process of both emulsion (p 673, col 1, ¶ 2), and reduces both G0N and ττB (p 677, col 1, ¶ 2).
The presence of polyvinyl pyrrolidone (PVP) is not disclosed.
Csempesz et al. discloses colloidal system have many potential uses in science and technology and a key application of liposomes in recent years has been in pharmaceutics (p 79, introduction). The belief is that the controlled stability and surface properties of dispersed particles in colloidal systems may enhance the efficacy or safety of existing drugs while the slow release properties may also provide selective and prolonged therapeutic activity (p 79, introduction). Suitable polymer coatings provide sterically stabilized liposomes with a longer lifetime in the blood while also reducing attractive forces and increasing the hardcore repulsion between the possible reactants (p 80, ¶ 2). A number of studies have demonstrated that liposomes containing phospholipids derivatized with relatively low molecular weight hydrophilic polymers such as PEG exhibit prolonged circulation but less attention has been paid to the use of high polymers [sic] in liposome stabilization (p 80, ¶ 3). The water soluble homopolymers methyl cellulose (MC), hydrolyzed poly(vinyl alcohol) and PVP proved to be efficient steric stabilizers for several colloidal dispersions (p 81, ¶ 1). The liposomes contained DMPC (dimyristoyl phosphatidylcholine) and DPPC (dipalmitoyl phosphatidylcholine; p 80, ¶ 3) that formed small unilamellar liposomes of narrow size distribution (p 82, ¶ 5). The dispersion of polymer containing vesicles were kinetically more stable than those of bare liposomes and the sorbed macromolecules decreased aggregation and/or fusion of liposomes during storage compared to bare liposomes (p 84, ¶ 3). The enhanced stability can be ascribed to the formation of a protective macromolecular sheathe around the vesicle which ensures steric stabilization against liposome aggregation (sentence bridging p 84 and 85). Uncharged polymers can be efficient stabilizers of vesicles and provide good control of the colloidal interaction and hence the kinetic stability of liposome dispersions (p 88, ¶ 5).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use a water soluble polymer such as PVP as disclosed by Csempesz et al. in the compositions of Nakarapanich et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Nakarapanich et al. discloses that the water-soluble polymer HEC had effects on the system such as delaying aging and Csempesz et al. discloses a water soluble polymer can form a protective macromolecular sheathe around the vesicle structures. One of ordinary skill in the art would be motivated to prepare liposomes that are as stable as possible and both Nakarapanich et al. and Csempesz et al. teach that polymer addition such as HEC or PVP can further increase stability. The amount of vesicle forming components, the amount of interaction between components (e.g., based on the chain length of the fatty alcohol and cationic surfactant) can alter the structures formed in the final composition so one of ordinary skill in the art would routinely optimize the amounts of the vesicle forming ingredients and the selection and amounts of ingredients such as HEC or PVP added to stabilize the structures present in the composition. “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See MPEP 2144.05. There is no evidence of record as to any unexpected results demonstrating the criticality of the claimed amounts.
Properties such as the diffusion constant Dapp, kurtosis constant Kapp and percent diffusion restricted water are not disclosed. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). “As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” MPEP 2113 Here compositions meeting the physical and structural limitations are disclosed by the prior art but the diffusion constant Dapp, kurtosis constant Kapp and percent diffusion restricted water were not measured but are determined by the structure of the composition. Absent evidence of record that the materials of Nakarapanich et al. do not possess these properties, the rejection of the claims requiring such properties will be maintained.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618