DETAILED ACTION
Claim Rejections - 35 USC § 112
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.
Claims 1-6 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement.
The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors include, but are not limited to:
The breadth of the claims;
The nature of the invention;
The state of the prior art;
The level of one of ordinary skill;
The level of predictability in the art;
The amount of direction provided by the inventor;
The existence of working examples; and
The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988); M.P.E.P. § 2164.01(a).
Claims 1-6 are directed to inter alia a cell cryopreservation hollow fiber membrane comprising a cellulose ester, such that the membrane is characterized by a breaking strength that is not substantially reduced (“80% or more”) by freezing and thawing. The claims are extremely broad, covering a membrane containing essentially any polymer composition comprising any cellulose ester (or combinations thereof) and any amount of that cellulose ester. The claims do not require any specific membrane dimensions, physical properties, or method of fabrication.
There is little direction provided by the inventor for how to operate within the full scope of the claims. Rather, the specification provides a narrow set of examples (Examples 1-3) that are each characterized by a specific set of parameters.
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The working devices of Examples 1-3 (see pages 16-24) are characterized by the same spinning dope polymer concentration, NMP/TEG ratio, nozzle diameter, temperatures, internal liquid, air gap, coagulation liquid concentration and temperature, and counter flow operation. Examples 1-3 are operated within a nozzle draft ratio of 0.58 to 0.77. Pages 16-18 of the specification identify that the raw resin is cellulose triacetate (CTA), and that the spinning dope includes NMP (solvent) and TEG (non-solvent). The membranes of Examples 1-3 are further characterized by a narrow area percentage range of 47-58%, a narrow roughness of 4.5-4.6 nm, a narrow inner diameter range of 188.5-222.2 microns, and a narrow film thickness of 25.2-38.4 microns (pre and post processing). See Tables 2-4. These Examples describe a hollow fiber membrane having very specific qualities produced by a very specific operation, and do not provide enabling support for the much broader scope of the claimed invention.
Furthermore, the claims are entirely open-ended with respect to freezing and thawing conditions, which would also affect the membrane breaking strength. A membrane that is frozen and thawed under a first set of conditions (e.g., temperature, duration, rate of change) will likely be characterized by a different post-operation final breaking strength than the same membrane that is frozen and thawed under a second set of conditions. This creates a situation where the same hollow fiber membrane may or may not read on the claimed invention based not on its own inherent qualities and characteristics, but rather on the particulars of the vitrification method it is subjected to (i.e., a hypothetical membrane may retain 80% breaking strength when subjected to “mild” vitrification freezing/thawing, but may not retain 80% breaking strength when subjected to “extreme conditions). Freezing and thawing play a large part in defining the claimed invention, however the conditions that characterize the freezing and thawing steps are not designated. This reduces predictability and the quantity of experimentation needed to make and use the invention.
It is noted that the Comparative Examples 1 and 2 are quite similar to Examples 1-3 regarding the composition of the spinning dope, but differ in how the polymers are processed (nozzle diameter, temperatures, internal liquid, air gap, coagulation liquid concentration and temperature). This leads to uncertainty and a lack of predictability because the specification does not appear to indicate specifically which change or changes in operation are responsible for the improved breaking strength result of the claimed invention. Even if the claims were directed to a specific polymer composition for making the hollow fiber membrane (which they are not), undue experimentation would still be necessary to determine what combinations of nozzle diameter, temperatures, internal liquid, air gap, coagulation liquid concentration and temperature, etc. produce membrane products characterized by the claimed retention of breaking strength following freezing and thawing.
Lastly, it is unclear what physical properties of the produced membrane account for the inventive effect – i.e., breaking strength preservation through freezing/thawing. Even those having a high level of skill in the art would experience difficulty in predicting which membrane structures successfully allow one to make and use the invention when the defining features of the membrane (thickness?, surface pore size?, average pore size?, polymer composition?, area percentage?) to which the claimed breaking strength is attributable are not clearly established.
In conclusion, the specification does not enable one of ordinary the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with the claims.
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.
Claims 1-6 are rejected under 35 U.S.C. 112(b) 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.
Independent claim 1 states that the hollow fiber membrane maintains at least 80% of its breaking strength following vitrification freezing and thawing. However, the freezing and thawing steps are not defined. A membrane that is frozen and thawed under a first set of conditions (e.g., temperature, duration, rate of change) will likely be characterized by a different post-operation final breaking strength than the same membrane that is frozen and thawed under a second set of conditions. This creates a situation where the same hollow fiber membrane may sometimes read on the claimed invention (and sometimes not) based on the particulars of the vitrification method it is subjected to at that time, as opposed to its own qualities and characteristics. A claim is rendered indefinite when a limitation of the claim (here, the final breaking strength) is defined by reference to a variable operation and the specifics of that operation are not sufficiently defined. See MPEP 2173.05(b)(II).
Claim Interpretation
The term “average area percentage” in claims 4 and 5 is understood to mean the proportion of solid portions of the membrane to hollow portions of the membrane. The term “area percentage” is used as an equivalent to “bulk density”. See pages 9 and 19 of the specification.
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.
Claims 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Nagashima (US 20180000067) in view of Takada (US 20200061545) and Xing “Fabrication and characterization of cellulose triacetate porous membranes by combined nonsolvent-thermally induced phase separation”.
With respect to claims 1 and 3, Nagashima discloses a cell cryopreservation hollow fiber membrane (Figure 10:30). Paragraphs [0005], [0040] and [0083] state that the hollow fiber membrane includes cellulose ester (“To contain and cryopreserve the germ cells, particularly, cellulose acetate is preferable, and cellulose diacetate is more preferable”). Because the Nagashima hollow fiber membrane is fabricated from the same material (cellulose ester) as the claimed hollow fiber membrane, it is believed to inherently be characterized by the same breaking strength. Nagashima, however, does not expressly teach that the breaking strength of the membrane following freezing and then thawing is at least 80% of the breaking strength during wetting before freezing.
Takada discloses a hollow fiber membrane comprising cellulose ester. Takada teaches in paragraphs [0013], [0048], [0158] and [0230] that the membrane is characterized by a high permeation performance and a high membrane strength due to the cellulose ester material.
Xing discloses a cellulose triacetate membrane and method of fabrication. The overall porosity, surface pore size and tensile strength of the membrane is controlled by varying reaction conditions, such as CTA concentration and coagulation temperature. For example, an outer surface of the membrane may be characterized by an average pore size that is 1.1 or more times greater than the average pore size of an inner surface. This is shown in at least Fig. 8a.
Before the filing date of the claimed invention, it would have been obvious to ensure that the Nagashima hollow fiber membrane does not lose breaking strength due to vitrification freezing (i.e., “the breaking strength of the membrane following freezing and then thawing is at least 80% of the breaking strength during wetting before freezing”). Takada teaches that hollow fiber membranes comprising a cellulose ester are characterized by improved mechanical strength, while still exhibiting high permeability and biocompatibility. Xing additionally shows that reaction conditions, such as temperature and polymer composition, may be adjusted to affect surface pore size, and that larger surface pores sizes may be advantageously formed as a means by which to preserve breaking strength following vitrification freezing and thawing. Based on the teachings of Takada and Xing, it would have been within the ability of one of ordinary skill to optimize the material composition of the Nagashima hollow fiber membrane, as well as reaction conditions during fabrication, in order to improve breaking strength following a cell freezing procedure.
With respect to claim 2, Nagashima, Takada and Xing disclose the combination as described above. Takada further shows that pore structure through the hollow fiber membrane is nonuniform in a thickness direction.
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Xing additionally teaches that nonuniform pores are created in a thickness direction of the membrane.
Claims 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Nagashima (US 20180000067) in view of Takada (US 20200061545) and Xing “Fabrication and characterization of cellulose triacetate porous membranes by combined nonsolvent-thermally induced phase separation” as applied to claim 1, and further in view of Jones (US 20180142199).
Nagashima, Takada and Xing disclose the combination as described above, however do not expressly describe an area percentage or average roughness of the hollow fiber membrane.
Jones discloses a hollow fiber membrane (Figure 3B:524) configured to support cells. Paragraph [0098] states that the pore structure that defines the membrane is “homogenous”, which reads on the limitation “a variation in an area percentage…is less than 5%”. Jones further teaches that an average area percentage occupied by the pores is 40% or more and 70% or less (“openings of the pores may be in the size range of about 0.5 to about 3 microns, and the number of pores on the outer surface of the fibers may be in the range of about 10,000 to about 150,000 pores per mm2”). Paragraph [0101] additionally indicates that the hollow fiber membrane may have a surface roughness of 20 nm or less (“the interior surface of the hollow fiber may have a surface roughness of between about 10 nanometers and about 100 nanometers, such as between about 20 nanometers and about 90 nanometers”).
Before the effective filing date of the claimed invention, it would have been obvious to optimize the area percentage and average roughness of the Nagashima hollow fiber membrane. Jones shows how these parameters may be adjusted to facilitate cell attachment and improve permeability. Jones demonstrates how it is known in the art to create homogenous pore structures and an interior average roughness of less than 20 nm through known manufacturing techniques.
Response to Arguments
In response to Applicant’s amendment filed 09 February 2026, the previous rejections have been withdrawn. However, upon further consideration, new grounds of rejection are made to address the amended claims.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN ANDREW BOWERS whose telephone number is (571)272-8613. The examiner can normally be reached M-F 7am-5pm.
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/NATHAN A BOWERS/ Primary Examiner, Art Unit 1799