DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 15, 2026 has been entered.
Previous Rejections
Applicant’s arguments, filed May 15, 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on May 19, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 3 – 8, 10 -11, 14, 20, 22 – 23, 26 – 27, 30, 34, and 37 – 39 are cancelled.
Claims 18 – 19, 21, 24 – 25, 28 – 29, 31 – 33, and 35 – 36 are withdrawn.
Claims 1 – 2, 9, 12 – 13, 15 – 17, and 40 – 44 are examined here-in.
Claim Objections
Claim 2 is objected to because of the following informalities:
Claim 2 recites “dipalmitoylphosphatidyl (DPPC)”. The parenthetical DPPC is dipalmitoylphosphatidylcholine, so this should be corrected or the abbreviation deleted.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 40 and 41 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Independent claim 1 recites “the excipient is polyethylene glycol 1000”. Dependent claim 40 recites “wherein the excipient is polyvinyl alcohol, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 1000, or propylene glycol” which fails to further limit the subject matter of the claim upon which it depends (claim 1).
Dependent claim 41 recites “wherein the excipient is polyethylene glycol 1000” which fails to further limit the subject matter of the claim upon which it depends (claim 41 depends on claim 40 depends on claim 1).
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
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 non-obviousness.
Claims 1 – 2, 9, 12 – 13, 15 – 17, and 40 – 44 are rejected under 35 U.S.C. 103 as being unpatentable over Abra (WO 01/05372 A2, of record) in view of Agnew (H. Agnew & M. Alviar-Agnew “Freezing point depression and boiling point elevation” Ch 13.9 LibreTexts, of record) and further in view of Brader (WO 2018/089540 A1).
Abra teaches a composition with a liposome, an inner medium, and an external medium that has improved protection from damage associated with freezing and thawing (abstract). Abra emphasizes that liposome stability is an important parameter for liposomal formulations (page 1 lines 23 – 27).
Abra teaches that each liposome in the composition has an entrapped aqueous medium and is suspended in an external medium which contains a salt and a cryoprotectant (page 3 lines 7-11). Abra teaches that the external medium has a higher osmolarity than the inner medium (page 3 lines 11-12). Abra teaches the cryoprotectant can be a sugar, glycerol, or polyethylene glycol (page 3 lines 15 – 22, page 25 lines 14 – 17).
In Example 2, Abra shows a composition with liposomes, a solution with 5% w/v sucrose and 0.9% w/v NaCl as an external medium, and an internal aqueous medium of 0.9% w/v NaCl, without sucrose (page 7 lines 16-22).
Abra teaches phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, and phosphatidylserine as lipids suitable for a liposome (page 20 lines 22-23).
Abra does not teach the freezing points of the internal and external media, the relative amount of composition encapsulated in the liposomes, or that the excipient is PEG1000 in an amount of 30 to 60% v/v of the external medium.
Agnew teaches a missing element of Abra.
Agnew teaches “A solution will have a lower freezing point than a pure solvent” because “the solute-solvent interactions prevent the solvent from going into the solid phase” (page 1).
Agnew’s teachings suggest that a medium with 5% w/v sucrose and 0.9% w/v NaCl will have a lower freezing point than a medium with 0.9% w/v NaCl because in the first case there is more solute in the solution, thus lowering the freezing temperature.
The combination of Abra and Agnew is prima facie obvious as combining prior art elements according to known methods to yield predictable results (MPEP 2143(i)(a)). Abra teaches a liposomal composition with aqueous internal and external media, where the external medium has increased osmolarity than the internal medium, i.e. Abra teaches each of the claimed components of the composition. A person of ordinary skill in the art would recognize that the increased osmolarity of the external medium relative to the internal medium would necessarily result in a depressed freezing temperature for the external medium relative to the internal medium, as taught generally by Agnew. The combination of Abra and Agnew is prima facie obvious as combining known ingredients according to known methods to yield predictable results (MPEP 2143(I)(a)).
The combination of Abra and Agnew does not teach the excipient is polyethylene glycol 1000 included the amount of 30 to 60% v/v of the external medium.
Brader teaches the missing element of the combination of Abra and Agnew.
Brader teaches a composition with lipid nanoparticles and a stabilizing agent that mitigates the degradation of lipid nanoparticles (abstract).
Brader teaches lipid nanoparticles should be protected from degradation by including a stabilizing agent in the composition (paragraphs 0080 – 0081). Brader teaches cryoprotectants are suitable stabilizing agents (paragraphs 0081, 0163).
Brader teaches PEG 1000 as a suitable polymer cryoprotectant (paragraphs 0015, 0164). Brader teaches the inclusion of cryoprotectant in the amount of 0.05 to 50% by weight (paragraphs 0015, 0167 – 0168).
The combination of Abra, Agnew, and Brader is prima facie obvious as combining prior art elements according to known methods to yield predictable results (MPEP 2143(i)(a)). A person of ordinary skill in the art would be motivated to modify the combination of Abra and Agnew to include the cryoprotectant as taught by Brader because inclusion of a cryoprotectant stabilizes the composition against degradation (paragraphs 0080 -0081, 0163). Furthermore, including a cryoprotectant is effectively increasing the amount of solute, which will drive freezing point depression, as taught by Agnew. The combination of Abra, Agnew, and Brader’s teachings would yield predictable results (i.e. a composition with liposomes that has a depressed freezing point and is stabilized by cryoprotectant) which is prima facie obvious.
The combination of Abra’s teachings of a liposomal solution with an external medium of which contains a higher osmolarity than the internal encapsulated medium (page 7 lines 16-22) with Agnew’s teachings about and increased amount of solute resulting in a lower freezing point (page 1), and further combined with Brader’s teaching for PEG 1000 as a cryoprotectant in the amount of 0.05 to 50% by weight (paragraphs 0015, 0164, 0167 – 0168) reads on instant claim 1. Brader’s teaching for PEG 1000 as a cryoprotectant in the amount of 0.05 to 50% by weight (paragraphs 0015, 0164, 0167 – 0168) overlaps on the instantly claimed amount of 30 to 60% v/v. Claimed ranges that overlap teachings of the prior art are prima facie obvious according to MPEP 2144.05(i).
Abra’s teaching of phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, and phosphatidylserine as lipids suitable for a liposome (page 20 lines 22-23) reads on claim 2 of the instant application.
In one example, Abra teaches that the volume of external medium is 85% of the total volume of the solution (page 30 line 8), therefore the liposomes and internal medium would necessarily make up the remaining 15% volume of the total solution. Although Abra does not explicitly teach that the encapsulated volume is a certain amount relative to the total volume of the composition, it would be within the expertise of a person of ordinary skill in the art to perform routine experimentation to arrive at the claimed range of 20 to 50% as recited in instant claim 9. Routine experimentation is prima facie obvious according to MPEP 2144.05(II)(a). Furthermore, changes in proportion do not render an invention patentably distinct from prior art according to MPEP 2144.04(IV)(a). In this case, Abra teaches the internal medium is less than 15% volume of the total composition which is not within the claimed range of 20 to 50% recited in instant claim 9 but is effectively merely a change in proportions.
Agnew teaches the following formula to calculate the freezing point decrease of a solution:
∆
T
=
k
f
*
m
*
i
Where
∆
T
is the change in temperature, kf is the freezing point depression constant (for water 1.86 °C/m), m is the molality of the solution, and i is the number of particles formed when the particle dissolves (page 3).
For Abra’s inner medium, 0.9% w/v NaCl aqueous solution the freezing point is -0.3 °C (NaCl MW 58.4 g/mol, density 2.16 g/mL, i = 2). For Abra’s external medium, 5% w/v sucrose and 0.9% w/v NaCl aqueous solution the freezing point is approximately - 0.5 °C (NaCl MW 58.4 g/mol, NaCl density 2.16 g/mL, NaCl i = 2, sucrose MW 342.3 g/mol, sucrose density 1.58 g/mL, sucrose i = 1). A freezing point of -0.3 °C for the internal medium overlaps on the claimed range of between – 2 °C and 0 °C recited in instant claim 12. Claimed ranges that overlap with the prior art are prima facie obvious according to MPEP 2144.05I(I).
Abra teaches that a preferred concentration of NaCl in the external medium is greater than 3% w/v (page 16 line 5) and explains that with higher NaCl concentrations, liposomes were more protected from freeze/thaw damage (page 11 lines 8-9). The Examiner has calculated that 7% w/v NaCl solution would have a freezing point of – 10 °C. Given Abra’s teaching that a preferred concentration of NaCl in the external medium is greater than 3% w/v (page 16 line 5) and teachings that higher NaCl concentrations lead to greater protection from freeze/thaw (page 11 lines 8-9) a person of ordinary skill in the art would have been motivated to optimize the amount of solute in external medium to reach a desired freezing point, such as that of – 20 °C to – 10 °C as recited in instant claim 13. Routine optimization and experimentation is prima facie obvious according to MPEP 2144.05(II)(a).
Instant claim 15 recites “The composition of claim 1, wherein the encapsulated first volume is configured to form a plurality of ice particles when the composition is cooled to a predetermined temperature”. The limitation of forming ice particles at a predetermined temperature is interpreted as a product-by-process limitation. Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps, thus the determination of patentability is based on the product itself (MPEP 2113). The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. In the instant case, Abra’s composition of liposomes encapsulating an internal medium and suspended in an external medium reads on the composition of claim 15 because freezing is an inherent property of solutions. Therefore, Abra’s composition of liposomes with an internal and external medium will necessarily form ice crystals at a freezing point specific to the solutions. As such, the patentability of the instant composition does not depend on its method of production, and the Applicant’s limitation regarding the process of forming ice particles at a predetermined temperature is not patentable, in view of Abra.
Instant claim 16 recites the ice particles comprise between about 30% and 50% by weight of the total composition. A person of ordinary skill in the art would have the expertise to formulate the claimed composition with the ice particles in the claimed range. Routine experimentation is prima facie obvious according to MPEP 2144.05(II)(a). Furthermore, changes in proportion do not render an invention patentably distinct from prior art according to MPEP 2144.04(IV)(a). In this instance, ice particles in the amount of 30 to 50% by weight of the total composition is a proportion that does not render the claimed invention patentably distinct from the prior art.
As discussed above with regards to claim 13, a person of ordinary skill in the art is able to perform routine calculations to determine the solute required for a given freezing point, therefore instant claim 17’s recitation of temperature between – 20 °C and – 5 °C is prima facie obvious (MPEP 2144.05(II)(a).
Abra’s teaching that the cryoprotectant can be a sugar, glycerol, or polyethylene glycol (page 3 lines 15 – 22, page 25 lines 14 – 17) and Brader’s teaching for PEG 1000 as a suitable polymer cryoprotectant (paragraphs 0015, 0164) reads on claims 40 and 41 of the instant application.
Brader’s teaching for cryoprotectant in the amount of 0.05 to 50% by weight (paragraphs 0015, 0167 – 0168) overlaps on the instantly claimed amounts of 30 to 50% v/v, 40 to 50% v/v, and about 47% v/v as recited in instant claims 42 – 44. Claimed ranges that overlap teachings of the prior art are prima facie obvious according to MPEP 2144.05(i).
Examiner’s Reply to Attorney Arguments Dated May 15, 2026
Applicant argues that the combination of Abra, Agnew, and Cabral-Lilly does not teach the limitations of the amended claim (Remarks pages 9 – 12). This argument is moot because the new ground of rejection addresses the claims as amended.
Conclusion
All claims are rejected. No claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Toriana N. Vigil whose telephone number is (571)270-7549. The examiner can normally be reached Monday - Friday 9:00 a.m. - 5:00 p.m. EST.
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/TORIANA N. VIGIL/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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