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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/25/20205 has been entered.
Response to Amendment
The amendment filed 11/25/20205 has been entered. Claims 1, 2, 4, 5-12, 14, 16-22 and 25-26 remain pending in the application, of which claims 6-12 have been withdrawn.
Response to Arguments
Applicant’s arguments, see Remarks, filed 11/25/20205, with respect to the rejection(s) of claim(s) 1 have been considered but are moot because the new ground of rejection does not rely on the combination of reasoning and teaching applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
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.
Claim 26 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 26 recites “The porous hollow fiber membrane of claim 1, wherein the N-alkyl- pyridinium groups have a counter ion, wherein the counter ion is monomethylsulfate”
There is no antecedent basis for this limitation.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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, 2, 4, 5, 14, 16-22 and 25 are rejected under 35 U.S.C. 103 as being obvious over US 2018/0154315 Al, hereinafter Berzinis, in view of Yang (J.M. Yang et al./Journal of Membrane Science 138 (1998) 19-27), hereinafter Yang, further in view of (Salamone, J.C., Ellis, E.J. (1973). Preparation of Cationic Polyelectrolytes by Spontaneous Polymerization. In: Bikales, N.M. (eds) Water-Soluble Polymers. Polymer Science and Technology, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-4583-1_17), hereinafter Salamone. A table of dependent Berzinis embodiments is provided for convenience.
Table 1. Selected Embodiments (Em) between [0045] – [0080] and relevant component group members.
[¶]
Em
Related Em
Relevant Components
[0046]
1
--
Polyethersulfone; polysulfone; a combination
[0051]
6
1-5
Polyvinylpyrrolidone; glycosaminoglycans such as heparin;
a combination
[0052]
7
1-6
amphiphilic block copolymer comprising:
a hydrophobic block and a hydrophilic block.
[0053]
8
1-7
polystyrene-block-poly( 4-vinylpyridine );
a combination thereof.
[0071]
25
7
the hydrophilic block or graft comprises an addition
polymer of 4-vinylpyridine; N-vinylpyrrolidone; combination
[0073]
27
20-26
porous asymmetric membrane
[0075]
29
27-28
hollow fiber configuration
[0078]
32
27-31
The membrane is a porous asymmetric hollow fiber.
[0079]
33
27-32
separation module
Regarding Claim 1, Berzinis Embodiment 33 (wherein the embodiments are related in the following manner: Em. 1 [Wingdings font/0xE0] Em. 6 [Wingdings font/0xE0] Em. 7 [Wingdings font/0xE0] Em. 25 [Wingdings font/0xE0] Em. 27 [Wingdings font/0xE0] Em. 29 [Wingdings font/0xE0] Em. 32 [Wingdings font/0xE0] Em 33; See Table 1 above and [0045] – [0080]) teaches a porous hollow fiber membrane (“separation module comprising the porous asymmetric membrane of any of embodiments 11-12 and 27-32”, [0079]; Embodiment 32: “the porous asymmetric membrane of any of embodiments 11-12 and 27-31, wherein the membrane is a porous asymmetric hollow fiber”, [0078]) having an anticoagulant immobilized thereon (Embodiment 6 “the polymer additive comprises polyvinylpyrrolidone…glycosaminoglycans such as heparin or heparin sulfate, or a combination comprising at least one of the foregoing.”, [0051]); the membrane comprising a blend of polymers (“A "combination" is inclusive of blends, mixtures, alloys, reaction products, and the like”, [0120]), wherein the blend of polymers comprises:
i) polysulfone, polyethersulfone or polyarylethersulfone (Em. 1; See Table 1 above and [0046]);
ii) polyvinylpyrrolidone (Em. 6; See Table 1 above and [0051]); and
iii) at least one additional polymer (Em. 7; See Table 1 above and [0052])).
Berzinis Embodiment 8 (wherein the embodiments are related in the following manner: Em. 1 [Wingdings font/0xE0] Em. 6 [Wingdings font/0xE0] Em. 7 [Wingdings font/0xE0] Em. 8; See Table 1 above and [0045] – [0053]) teaches Embodiment 7, wherein the additional polymer is capable of bearing one or more ammonium groups (“polystyrene-block-poly( 4-vinylpyridine ), or a combination thereof”, [0053]; “A "combination" is inclusive of blends, mixtures, alloys, reaction products, and the like”, [0120]), and wherein the additional polymer comprises a reaction product of
b) a copolymer of vinylpyridine and styrene (“polystyrene-block-poly( 4-vinylpyridine ), or
a combination thereof.”, [0053]; “A "combination" is inclusive of blends, mixtures, alloys, reaction products, and the like”, [0120])
Berzinis also teaches “a first non-solvent composition comprising water, a water-miscible polar aprotic solvent, or a combination comprising at least one of the foregoing, and a polymer additive dissolved in the first non-solvent composition”
While Berzinis is silent on ionic bonds, both Berzinis Em. 8 and Em 33 teach combinations, and Berzinis further teaches “A "combination" is inclusive of blends, mixtures, alloys, reaction products, and the like” ([0120]), which provides motivation for the ammonium group of vinyl pyridine to be capable of reaction.
Berzinis does not teach an alkylating agent.
However, Yang teaches a reaction product of a copolymer of styrene and vinylpyridine with an alkylating agent (“Then the substituted pyridine groups on the SBS-g-VP graft copolymer
membrane were quaternized with iodomethane”, Sec 1 p 2 Col 1 ¶5), wherein anticoagulant forms an ionic bond with one or more ammonium groups of the polymer (“heparin being ionic bonded onto the quaternized pyridine groups on the SBS-g-VP”, Sec. 4) and Salamone teaches that while both methyl sulfate and methyl iodide are alkylating agents known to form quaternization reactions of vinylpyridines, dimethyl sulfates are advantageous: “quaternization reactions …with dimethyl sulfate, in particular, are quite rapid, and high-molecular-weight products apparently result. The reactions with methyl iodide are much slower, and even with a greater ratio of alkylating agent to monomer than was used with dimethyl sulfate, only relatively low-molecular weight products result”, Table 1, p 4 ¶1.
Berzinis is analogous art because Berzinis addresses the problem of “An improved method of making a porous asymmetric membrane” (Berzinis [0005]), wherein “the porous asymmetric membranes made by the method, and separation modules fabricated from the porous asymmetric membranes made by the method, can advantageously be used in medical, pharmaceutical, biotechnological, or food processes, for example the removal of salts and/or low molecular weight organic impurities from aqueous streams by ultrafiltration” (Berzinis [0043]) wherein “ The aqueous stream can be human blood” (Berzinis [0043]) and “Specific medical applications include the concentration and purification of peptides in blood plasma; hemofiltration; hemodialysis; hemodiafiltration; and renal dialysis” (Berzinis [0043]).
Yang is analogous because Yang addresses the problem of quaternization of styrene-vinyl pyridine copolymers and the effect of pyridine amount on the ionically bonded anticoagulant concentration (Yang Sec. 3.2; Sec 4).
Salamone is analogous art because Salamone addresses the same problem of quaternization of polyvinylpyridine.
It would have been obvious to one of ordinary skill in the art, before the effectively filed date, to combine the embodiments of Berzinis, particularly in regards to heparin, with the ionic bonding of heparin and quaternized copolymer of Yang at least to provide antithrombic activity on the membrane, particularly via the advantageous alkylating agent of Salomane (Salamone p 4 ¶1). Doing so would be compatible with the expected environment of use, wherein “the porous asymmetric membranes made by the method, and separation modules fabricated from the porous asymmetric membranes made by the method, can advantageously be used in medical… processes, for example the removal of salts and/or low molecular weight organic impurities from aqueous streams by ultrafiltration” (Berzinis [0043]) wherein “ The aqueous stream can be human blood” (Berzinis [0043]) and “Specific medical applications include the concentration and purification of peptides in blood plasma; hemofiltration; hemodialysis; hemodiafiltration; and renal dialysis” (Berzinis [0043]), “heparin being ionic bonded onto the quaternized pyridine groups”, (Yang Sec. 4).
Regarding Claim 2, Berzinis does not positively recite an alkylating agent.
However, Yang teaches the ammonium groups are N-alkylpyridinium groups (“Then the substituted pyridine groups on the SBS-g-VP graft copolymer membrane were quaternized with iodomethane”, Sec 1 p 2 Col 1 ¶5).
Regarding Claim 4, Berzinis does not positively recite an alkylating agent.
However, Yang teaches alkylated pyridine groups (“Then the substituted pyridine groups on the SBS-g-VP graft copolymer membrane were quaternized with iodomethane”, Sec 1 p 2 Col 1 ¶5), and “It was also found that the heparin concentration on the SBS-g-VP-HEP increased with
the increasing amount of VP grafted onto the SBS membrane.” (p 4 Sec. 3.2 and Table 2).
MPEP 2144.05 (III)(A) states “Where the issue of criticality is involved, the applicant has the burden of establishing his position by a proper showing of the facts upon which he relies”
Therefore, it would have been obvious to one of ordinary skill in the art, before the effectively filed date, for modified Berzinis to adopt Yang’s routine optimization of the polymerization method to adjust the amount of alkylated groups (Yang Tables 1-2) with reasonable expectation of achieving desired heparin concentration (See MPEP 2144.05 II). Doing so would grant the ability to fine-tune the heparin content on the copolymer.
Regarding Claim 5, Berzinis does not positively recite an average molecular weight
Salamone teaches a high viscosity methylated 4-VP product (Table 1), where viscosity can be used to find molecular weight via the Mark-Houwink Equation; and Salamone also supports modified alkylation agent/monomer ratio and solvent amount to the molecular weight to result in optimized molecular weight: “The ratios of alkylating agents to vinyl monomers and the amount of solvent were varied in order to determine the most favorable conditions for the formation of high-molecular-weight polymers” p 3 and Tale 1.
Yang also motivates higher molecular weight, given “It was also found that the heparin concentration on the SBS-g-VP-HEP increased with the increasing amount of VP grafted onto the SBS membrane.” (p 4 Sec. 3.2 and Table 2).
MPEP 2144.05 (III)(A) states “Where the issue of criticality is involved, the applicant has the burden of establishing his position by a proper showing of the facts upon which he relies”
Therefore, it would have been obvious to one of ordinary skill in the art, before the effectively filed date, for modified Berzinis to adopt Salamone’s routine optimization of the polymerization method to optimize via modified polymerization reaction parameters with reasonable expectation of achieving desired average molecular weight (See MPEP 2144.05 II). Doing so would grant the ability to fine-tune the polymer characteristics, as demonstrated in Salamone Table 1.
Regarding Claim 14, Berzinis suggests the membrane is configured as a plurality of membranes in a hemodialyzer (“the porous asymmetric membranes made by the method, and separation modules fabricated from the porous asymmetric membranes made by the method, can advantageously be used in medical… processes…Specific medical applications include the concentration and purification of peptides in blood plasma; hemofiltration; hemodialysis; hemodiafiltration; and renal dialysis”, Berzinis [0043]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effectively filed date, for the separation module of modified Berzinis to be configured as a hemodialyzer environment specifically, with no unexpected results.
Regarding Claim 16, Berzinis suggests a method for extracorporeal treatment of blood of a patient, said method comprising the step of passing the blood through the porous hollow fiber membrane of claim 1 to treat the blood (“the porous asymmetric membranes made by the method, and separation modules fabricated from the porous asymmetric membranes made by the method, can advantageously be used in medical… processes… for example the removal of salts and/or low molecular weight organic impurities from aqueous streams by ultrafiltration…The aqueous stream can be human blood …Specific medical applications include the concentration and purification of peptides in blood plasma; hemofiltration; hemodialysis; hemodiafiltration; and renal dialysis”, Berzinis [0043]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effectively filed date, for the hollow fiber membrane separation module of modified Berzinis to be used for treatment of blood, with no unexpected results.
Regarding Claim 17, Berzinis suggests the membrane is configured as a plurality of membranes in a filtration device (“the porous asymmetric membranes made by the method, and separation modules fabricated from the porous asymmetric membranes made by the method, can advantageously be used in medical… processes…Specific medical applications include the concentration and purification of peptides in blood plasma; hemofiltration; hemodialysis; hemodiafiltration; and renal dialysis”, Berzinis [0043]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effectively filed date, for the separation module of modified Berzinis to be configured as a filtration device environment specifically, with no unexpected results.
Regarding Claim 18, Berzinis suggests the membrane is configured as a plurality of membranes in a diffusion device (“the porous asymmetric membranes made by the method, and separation modules fabricated from the porous asymmetric membranes made by the method, can advantageously be used in medical… processes…Specific medical applications include the concentration and purification of peptides in blood plasma; hemofiltration; hemodialysis; hemodiafiltration; and renal dialysis”, Berzinis [0043]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effectively filed date, for the separation module of modified Berzinis to be configured in a diffusion environment specifically, with no unexpected results.
Regarding Claim 19, Berzinis suggests the membrane is configured as a plurality of membranes in a hemodialyzer (“the porous asymmetric membranes made by the method, and separation modules fabricated from the porous asymmetric membranes made by the method, can advantageously be used in medical… processes…Specific medical applications include the concentration and purification of peptides in blood plasma; hemofiltration; hemodialysis; hemodiafiltration; and renal dialysis”, Berzinis [0043]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effectively filed date, for the separation module of modified Berzinis to be configured as a hemodialyzer environment specifically, with no unexpected results.
Regarding Claim 20, Berzinis suggests the method is performed via a hemodialysis procedure, hemodiafiltration, or hemofiltration (“the porous asymmetric membranes made by the method, and separation modules fabricated from the porous asymmetric membranes made by the method, can advantageously be used in medical… processes…Specific medical applications include the concentration and purification of peptides in blood plasma; hemofiltration; hemodialysis; hemodiafiltration; and renal dialysis”, Berzinis [0043]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effectively filed date, for the separation module of modified Berzinis to be used for treatment of blood via at least hemodialysis specifically, with no unexpected results.
Regarding Claim 21, Berzinis suggests the method is performed via a hemodiafiltration procedure (“the porous asymmetric membranes made by the method, and separation modules fabricated from the porous asymmetric membranes made by the method, can advantageously be used in medical… processes…Specific medical applications include the concentration and purification of peptides in blood plasma; hemofiltration; hemodialysis; hemodiafiltration; and renal dialysis”, Berzinis [0043]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effectively filed date, for the separation module of modified Berzinis to be used for treatment of blood via at least hemodiafiltration specifically, with no unexpected results.
Regarding Claim 22, Berzinis suggests the method is performed via a hemofiltration procedure, (“the porous asymmetric membranes made by the method, and separation modules fabricated from the porous asymmetric membranes made by the method, can advantageously be used in medical… processes…Specific medical applications include the concentration and purification of peptides in blood plasma; hemofiltration; hemodialysis; hemodiafiltration; and renal dialysis”, Berzinis [0043]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effectively filed date, for the separation module of modified Berzinis to be used for treatment of blood via at least hemofiltration specifically, with no unexpected results.
Regarding Claim 25, Berzinis is silent on heparin concentration.
However, Yang teaches that for 2.6 g of quaternized VP in a polystyrene copolymer, the anticoagulation has a surface concentration in the range of 588 IU/m2 (Table 2), given IU for heparin sodium is 7.14 mcg/IU and teaches “It was also found that the heparin concentration on the SBS-g-VP-HEP increased with the increasing amount of VP grafted” (Sec 3.2). This suggests that an anticoagulation surface concentration for double the Yang VP amount in a polystyrene copolymer, as taught in Park, would range from 1,000 to 30,000 IU/m2.
MPEP 2144.05 (III)(A) states “Where the issue of criticality is involved, the applicant has the burden of establishing his position by a proper showing of the facts upon which he relies”
It would have been obvious to one of ordinary skill in the art, before the effectively filed date, that increased concentration of quaternary vinylpyridine groups would allow for increased concentration of ionically bonded heparin (“heparin being ionic bonded onto
the quaternized pyridine groups on the SBS-g-VP”, Yang Sec. 4). That knowledge may be used to optimize the heparin concentration according to design need for optimal antithrombic conditions.
Regarding Claim 26, Berzinis is silent to a monomethylsulfate counterion.
However, Salamone teaches “4-vinylpyridine (4VP) with either dimethyl sulfate or methyl iodide… to determine the most favorable conditions for the formation of high-molecular- weight polymers. The water-soluble products… poly(4-vinyl-N-methylpyridinium methylsulfate) (VII, X- = CH3SO4-) and iodide (VIII, X- = I-)” (p. 3 ¶3).
It would have been obvious to one of ordinary skill in the art, before the effectively filed date, that using the methylating agent of dimethyl sulfate would predictably result in the water soluble product of poly(4-vinyl-N-methylpyridinium methylsulfate) (VII, X- = CH3SO4-).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
R. I. Leininger, C. W. Cooper, R. D. Falb, G. A. Grode. “Nonthrombogenic Plastic Surfaces” Science. Vol 152, p 1625-1626 (1966). Teaches Nonthrombogenic Plastic
Surfaces after heparinization of quaternized 4-VP.
Roy Biran, Daniel Pond. Advanced Drug Delivery Reviews 112 (2017) 12–23. Accessed July 20, 2025. http://dx.doi.org/10.1016/j.addr.2016.12.002. Teaches heparin coatings for medical application compatibility
Jen-Ming Yang et al. Preparation and characterization of heparin-containing SBS-g-DMAEMA copolymer membrane. Jour. Biomed. Mat. Research. 1998 , 86-91, John Wiley & Sons, Inc. Teaches effect on grafting and heparinization on protein adsorption to polymers.
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MARRIAH ELLINGTON
Examiner
Art Unit 1773
/RICHARD C GURTOWSKI/Primary Examiner, Art Unit 1773
03/17/2026