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 .
Applicant’s arguments, filed 10/22/2025, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
Claim Status
Claims 1, 2, 6, 9-15, and 19-28, are pending.
Claims 1, 2, 6, 9-11, 13, and 14, are withdrawn.
Claim Objections
Claim 23 is objected to because of the following informalities: “Human” should be lower case. Appropriate correction is required.
Claim 27 is objected to because of the following informalities: “administering the complex nasally or pulmonary” should read “administering the complex via nasal or pulmonary administration” or similar. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or pre-AIA 2nd ¶
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 24 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 24 recites the limitation "the other components" in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 24 depends from claim 12, where there is no mention of “other components.” For purposes of examination, the claim will be interpreted as wherein the weight percentage of the ionic polymer… is greater than the weight percentage of the proteinaceous agent.
Claim 24 also recites the limitation “the formulation” in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 24 depends from claim 12, where there is no mention of “the formulation.” For purposes of examination, the claim will be interpreted as of the complex.
Claim Rejections - 35 USC § 112(d) or pre-AIA 4th ¶
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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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.
Claim 19 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, 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. Claim 19 recites “wherein R1 represents a methyl group,” which is not further limiting of N,N dimethyl amino ethyl methacrylate, which comprises a methyl group in the R1 position. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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 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.
Claims 12 and 19, are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Foster et al (Bioconjugate Chem., 2010, 21(12): 2153-2362, cited on IDS dated 04/09/2023), as evidenced by Cymit (Poly[2-dimethylamino)ethyl methacrylate) and Zanata et al (Eur. Poly. Jour., 2022, 162, pp. 1-13).
Foster et al disclose an ionic polydimethylamionethyl methacrylate (PDMAEMA) polymer complexed to anionic PAA ovalbumin (proteinaceous antigen) conjugates, wherein cationic PDMAEMA was synthesized for nanoparticle formation by ionic complexation with anionic PPAA ovalbumin conjugates (abs, pg. 2206 1st col 2nd ¶). PDMAEMA was added at pH 7.4 where it was charged (pg. 2206 1st col last ¶). As evidenced by Cymit, polydimethylamionethyl methacrylate (PDMAEMA) is also known as N,N-dimethylaminoethyl methacrylate polymer. As evidenced by Zanata et al, PDMAEMA has a pKa between 7 and 7.5 (pg. 1 2nd col). The complexes were used as vaccines and were administered to treat mice (pg. 2208 1st col last ¶).
Regarding the complex of claim 12, where the PDMAEMA polymer disclosed by Foster et al is made up of DMAEMA monomers, and is the only polymer used to complex the ovalbumin conjugates, the limitation of a homopolymer of repeating units of DMAEMA (i.e., the PDMAEMA) is met. Further, the examiner notes that the molar ratio of claim 12 is in relation to a different repetitive unit of formula (I). Accordingly, where no other repetitive units of formula (I) are present, DMAEMA makes up the entirety of the molar ratio. In other words, the molar ratio of DMAEMA in the ionic polymer compared to a different repetitive unit of formula (I) (none appear to be present) is necessarily greater than 75%.
Regarding the method of claim 12, the complexes were administered to mice as vaccines, thereby reading on administering to an animal in need of treatment, as instantly claimed.
Regarding the mean pKa of claim 12, PDMAEMA has a pKa between 7 and 7.5, as evidenced by Zanata et al above, thereby meeting the claimed limitation.
Regarding the proteinaceous agents of claim 12, where the complexes of Foster et al comprise ovalbumin (proteinaceous agent and antigen), and are used as an active agent for vaccines, the newly added limitations are met.
Regarding claim 19, N,N dimethyl amino ethyl methacrylate comprises a methyl group in the R1 position of instantly claimed formula (I), and accordingly, the limitations are met.
Response to Arguments
First, Applicants assert Foster et al do not disclose or suggest a single polymer structure as now claimed and assert Foster et al teaches a system where two distinct polymers are used to form particles. Applicants also assert there is no indication that a single polymer contains greater than 75% DMAEMA. Second, Applicants assert the claims require the proteinaceous agent be medically or veterinary active, and asserts ovalbumin is not representative of a therapeutic agent.
First, respectfully, this argument is not persuasive. As amended, claim 12 does not require a single polymer structure where the complex “comprises” N,N dimethyl amino ethyl methacrylate. The examiner notes that comprising is open language and can include additional unrecited elements. Further, claim 12 recites that the molar ratio of N,N dimethyl amino ethyl methacrylate is greater than 75% in relation to a different repetitive unit of formula (I), which suggests that other polymers of formula (I) can be included. Regarding the percent of the DMAEMA, as discussed above, where no other repetitive units of formula (I) are present, DMAEMA makes up the entirety of the molar ratio. In other words, the molar ratio of DMAEMA in the ionic polymer compared to a different repetitive unit of formula (I) (none appear to be present) is necessarily greater than 75%.
Second, respectfully, this argument is not persuasive. Foster et al teaches ovalbumin as an antigen for vaccination purposes and has therapeutic activity. As such, it appears the limitation of at least one medically or veterinary active proteinaceous agent is met.
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.
Claims 15 and 22-24, are rejected under 35 U.S.C. 103 as being unpatentable over Foster et al (Bioconjugate Chem., 2010, 21(12): 2153-2362, cited on IDS dated 04/09/2023), as applied to claims 12 and 19 above, and further in view of Kabanov et al (US 20190111109 A1).
Foster et al are discussed above and further contemplates the use of this compositions against true therapeutic targets, including human tumor xenografts, etc. (pg. 2210 2nd col 1st ¶).
Foster et al do not specifically disclose the further inclusion of a surfactant, wherein the complex has been submitted to a drying process, wherein the treatment is administered to a human, nor wherein the weight percent of the polymer is the majority component.
Kabanov et al teach polyelectrolyte complexes for delivery of agents to a subject, wherein the agents are therapeutic agents such as polypeptides and proteins (abs, ¶ 5). The complexes comprise a synthetic polymer and the therapeutic agent, wherein the polymer may be a homopolymer, etc. (¶ 5, ¶ 74). The homopolymer may have a net positive charge (¶ 74). Suitable polymers with a net positive charge include N,N-dimethylaminoethyl methacrylate (¶ 76). As evidenced by Zanata et al, poly(N,N-dimethylaminoethyl methacrylate) has a pKa between 7 and 7.5 (pg. 1 2nd col). The complexes may contain any suitable agent, e.g., a polypeptide, including, but not limited to, enzymes, antibodies or antibody fragments, hormones, cytokines (¶¶ 88, 89). The complexes provide improved delivery and/or retention of the therapeutic agents (¶ 5). Administration of the polyelectrolyte complexes of the present invention to a human subject or an animal in need thereof can be by any means known in the art for administering compounds for medical and veterinary applications (¶¶ 102, 119). Emulsifiers can be included for poorly soluble compounds, including phosphatidylcholines and lecithin (¶ 116). The formulations can comprise dispersing agents, adjuvants, etc. (¶ 100). The complexes can be freeze-dried (lyophilized) (¶ 105). In some embodiments, the proteinaceous agent is included at 1 mg/ml and the polymer at 2 mg/ml (¶ 96). The complexes can be encapsulated, enteric-coated for selective disintegration in the gastrointestinal tract, etc. (¶ 108). The compositions can be administered intranasally, to the lungs, topically, etc. (¶¶ 103, 107).
Regarding claim 15, it would have been obvious to include an emulsifier or dispersing agent, such as phosphatidylcholine, to the complex of Foster et al, where these emulsifiers were known to be include into complexes that can comprise PDMAEMA and a proteinaceous agent, as taught by Kabanov et al, where the skilled artisan would recognize that emulsifiers or dispersing agents can be used in order to optimize the surface properties of the proteinaceous agents for stability, compatibility, etc. Further, it appears the emulsifying agents and dispersing agents taught by Kabanov et al read on surfactants, where the instant specification defines surfactants as any compound that is capable of altering surface properties of a given phase towards another phase, and phosphocholine derivatives (i.e., phosphatidylcholine) are disclosed as suitable surfactants (see ¶ 13 of the instant specification).
Regarding claim 22, it would have been obvious to modify the complex in the method made obvious above, by formulating a freeze-dried composition comprising the complex, a known storage method for polymeric complexes comprising proteinaceous agents, as taught by Kabanov et al.
Regarding claim 23, while Foster et al do not each delivering the complexes comprising proteinaceous agents to a human, and instead teaches administration to mice, Foster et al contemplates future studies for treating human tissues. The skilled artisan would recognize that the goal from administration of the complexes to mice, would be to extend those treatments to human subjects. Accordingly, where complexes comprising N,N-dimethyl amino ethyl methacrylate with a proteinaceous agent were known to be suitable for administration to humans, it would have been obvious for the skilled artisan to administer the complexes of Foster et al to a human for medical treatment, where both are directed to complexes comprising N,N-dimethyl amino ethyl methacrylate with a proteinaceous agent for medical treatments.
Regarding claim 24, it would have obvious to modify the complex of Foster et al with known ratios suitable for polymer complexes comprising proteinaceous agents, such as 2:1 (2 mg/ml polymer to 1 mg/ml proteinaceous agent), as taught by Kabanov et al, thereby appearing to read on the limitation of wherein the polymer by weight percent is the majority component.
Response to Arguments
First, Applicants assert that because Foster et al do not anticipate claim 12, Foster et al cannot serve as a valid base reference for the rejection. Applicants assert that even assuming arguendo that Foster et al does disclose the complex, Kabanov et al limits surfactant use to poorly water-soluble compounds, and asserts that PDMAEMA is known for its high solubility in aqueous environments. Accordingly, Applicants assert the skilled artisan would not have motivation to introduce a surfactant.
Second, Applicants assert Foster et al is silent regarding a drying process.
Third, Applicants assert that Foster et al’s teachings on mice cannot be extended to humans.
Fourth, Applicants assert Foster et al teaches specific charge ratios between PPAA/OVA and PDMAEMA between 1:1 and 60:1, suggesting less PDMAEMA than the proteinaceous compound.
First, respectfully, this argument is not persuasive. As discussed above and contrary to Applicants’ assertion, it appear that Foster et al do anticipate claim 12 for the same reasons discussed above and of record. Regarding the surfactant, while Kabanov et al do disclose embodiments with dispersing agents (i.e., surfactants) for poorly water-soluble compounds, the reference more broadly teaches the formulations can optionally comprise additional agents including medicinal agents, pharmaceutical agents, carriers, adjuvants, dispersing agents, diluents, and the like (¶ 100). It would have been obvious to include an emulsifier or dispersing agent, to the complexes of Foster et al, in order to emulsify the desired proteinaceous agent, as taught by Kabanov et al, where a skilled artisan would recognize that the inclusion of emulsifiers or dispersing agents are a way to include various proteinaceous agents with varying surface properties for compatibility with the complex made obvious above.
Second, respectfully, this argument is not persuasive. Kabanov et al are newly cited to address this newly added limitation and is obvious for the same reasons discussed above.
Third, respectfully, this argument is not persuasive. As discussed above, while Foster et al do not each delivering the complexes comprising proteinaceous agents to a human, and instead teaches administration to mice, Foster et al contemplates future studies for treating human tissues. The skilled artisan would recognize that the logical progression from administration of the complexes to mice, would be to extend those treatments to human subjects. Accordingly, where complexes comprising N,N-dimethyl amino ethyl methacrylate with a proteinaceous agent were known to be suitable for administration to humans, it would have been obvious for the skilled artisan to administer the complexes of Foster et al to a human for medical treatment, where both are directed to complexes comprising N,N-dimethyl amino ethyl methacrylate with a proteinaceous agent for medical treatments.
Fourth, respectfully, this argument is not persuasive. While Foster et al may disclose embodiments with less PDMAEMA than the proteinaceous compound, Kabanov et al is cited above for teaching that it was known to formulate polymeric complexes comprising a proteinaceous agent, wherein the polymer is the majority component. Accordingly, it would have been obvious to modify Foster et al by including N,N dimethyl amino ethyl methacrylate as the majority component for the same reasons discussed above.
Claims 20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Foster et al (Bioconjugate Chem., 2010, 21(12): 2153-2362, cited on IDS dated 04/09/2023), as applied to claims 12 and 19 above, and further in view of Wilson et al (ACS Nano, 2013, 7, 5, pp. 3912-3925, cited on IDS dated 04/09/2023).
Foster et al are discussed above but do not teach wherein the proteinaceous agent is an antigenic peptide nor wherein the complex further comprises an adjuvant of instant claims 20 and 21.
Wilson et al teach pH responsive nanoparticle vaccines where it was known to formulate polymeric complexes comprising DMAEMA (i.e., N,N-dimethyl amino ethyl methacrylate) for the co-delivery of proteinaceous antigens and immunostimulatory oligonucleotides (abs). Dual delivery of proteinaceous antigens and immunostimulatory oligonucleotides from the polymer complexes were known to significantly increase immune response (abs). In a particular embodiment, DMAEMA as the primary component (97%) (pg. 3913).
Regarding claims 20 and 21, it would have been obvious to modify the complex in the method made obvious above, by selecting from other known protein based therapeutic agents that are suitable for polymeric complexes for administering to a subject for medical treatment, such as proteinaceous antigens, as taught by Wilson et al. Additionally, it would have been obvious to further include an oligonucleotide adjuvant, where the dual delivery of proteinaceous antigens and oligonucleotide adjuvant from polymeric complexes comprising N,N-dimethyl amino ethyl methacrylate were known to significantly increase immune response, as contemplated by Foster et al and taught by Wilson et al.
Response to Arguments
Applicants assert Foster et al fail to teach adjuvants, especially in the form of oligonucleotides.
Respectfully, this argument is not persuasive. Wilson et al is newly cited to address the new claim limitation.
Claims 12, 15, 19, 22-25, 27, and 28, are rejected under 35 U.S.C. 103 as being unpatentable over Kabanov et al (US 20190111109 A1), as evidenced by Zanata et al (Eur. Poly. Jour., 2022, 162, pp. 1-13).
Kabanov et al are discussed above and are repeated here for convenience. Kabanov et al teach polyelectrolyte complexes for delivery of agents to a subject, wherein the agents are therapeutic agents such as polypeptides and proteins (abs, ¶ 5). The complexes comprise a synthetic polymer and the therapeutic agent, wherein the polymer may be a homopolymer, etc. (¶ 5, ¶ 74). The homopolymer may have a net positive charge (¶ 74). Suitable polymers with a net positive charge include N,N-dimethylaminoethyl methacrylate (¶ 76). As evidenced by Zanata et al, poly(N,N-dimethylaminoethyl methacrylate) has a pKa between 7 and 7.5 (pg. 1 2nd col). The complexes may contain any suitable agent, e.g., a polypeptide, including, but not limited to, enzymes, antibodies or antibody fragments, hormones, cytokines (¶¶ 88, 89). The complexes provide improved delivery and/or retention of the therapeutic agents (¶ 5). Administration of the polyelectrolyte complexes of the present invention to a human subject or an animal in need thereof can be by any means known in the art for administering compounds for medical and veterinary applications (¶¶ 102, 119). Emulsifiers can be included for poorly soluble compounds, including phosphatidylcholines and lecithin (¶ 116). The formulations can comprise dispersing agents, adjuvants, etc. (¶ 100). The complexes can be freeze-dried (lyophilized) (¶ 105). In some embodiments, the proteinaceous agent is included at 1 mg/ml and the polymer at 2 mg/ml (¶ 96). The complexes can be encapsulated, enteric-coated for selective disintegration in the gastrointestinal tract, etc. (¶ 108). The compositions can be administered intranasally, to the lungs, topically, etc. (¶¶ 103, 107).
Regarding the complex of claim 12, it would have been obvious to formulate the polyelectrolyte complex of Kabanov et al with a homopolymer of N,N-dimethylaminoethyl methacrylate complexed with a proteinaceous agent (i.e., polypeptides, proteins), as taught by Kabanov et al. Further, where the polymer made obvious above is a homopolymer, the homopolymer consists of repeating units of N,N-dimethylaminoethyl methacrylate.
Regarding the mean pKa of claim 12, poly(N,N-dimethylaminoethyl methacrylate) has a pKa between 7 and 7.5, as evidenced by Zanata et al above, which is made obvious by Kabanov et al above, thereby meeting the claimed limitation.
Regarding the molar ratio, where the polymer is a homopolymer, the N,N-dimethylaminoethyl methacrylate repeating monomers necessarily have a molar ratio relative to a different repetitive unit of formula (I) of greater than 75%.
Regarding the proteinaceous agent of claim 12, it would have been obvious to select from suitable proteinaceous agents, such as cytokines, hormones, enzymes, etc., as taught by Kabanov et al.
Regarding the method of claim 12, it would have been obvious administer the complex made obvious above to a human or animal in need thereof for medical treatment, as taught by Kabanov et al.
Regarding claim 15, it would have been obvious to include an emulsifier or dispersing agent, such as phosphatidylcholine, to the complexes of Kabanov et al, in order to emulsify the desired proteinaceous agent, as taught by Kabanov et al, where a skilled artisan would recognize that the inclusion of emulsifiers or dispersing agents are a way to include various proteinaceous agents with varying surface properties for compatibility with the complex made obvious above. Further, it appears the emulsifying agents and dispersing agents taught by Kabanov et al read on surfactants, where the instant specification defines surfactants as any compound that is capable of altering surface properties of a given phase towards another phase, and phosphocholine derivatives (i.e., phosphatidylcholine) are disclosed as suitable surfactants (see ¶ 13 of the instant specification).
Regarding claim 19, N,N-dimethylaminoethyl methacrylate comprises a methyl group in the R1 position of instantly claimed formula (I), accordingly, the limitations are met.
Regarding claim 22, where the claims are directed to a method of treating a subject comprising the complex made obvious above, the process of formulating the complex are simply product by process limitations or intended use limitations. Here, where the method made obvious above comprises a complex that can be in the form of a dry powder, it appears the product by process or intended use limitations are met where the drying process is simply a method of drying the composition to be used in the treatment methods. Nevertheless, were Kabanov et al teaches the complexes can be freeze-dried, it would have been obvious for the skilled artisan to freeze dry the complexes made obvious above.
Regarding claim 23, it would have been obvious to administer the complex in the method made obvious above to a human, as taught by Kabanov et al.
Regarding claim 24, where Kabanov et al disclose working embodiments comprising a 2:1 weight ratio of polymer to proteinaceous agent (2 mg/ml to 1 mg/ml), when formulating the complex made obvious above, it would have been obvious to start with those ratios from the working examples and adjust from there in order to achieve desired optimal structure and properties. Accordantly, the limitation of wherein the polymer by weight percentage is the majority component appears to be met.
Regarding claim 25, it would have been obvious to encapsulate or coat the complex in an enteric coating (i.e., encapsulate) for selective disintegration in the gastrointestinal tract, as taught by Kabanov et al.
Regarding claim 27, it would have been obvious to administer the complex in the method made obvious above by nasal administration or pulmonary administration, as taught by Kabanov et al.
Regarding claim 28, it would have been obvious to administer the complex in the method made obvious above by topical administration, as taught by Kabanov et al.
Response to Arguments
First, Applicants assert Kabanov et al mentions DMAEMA, but only as one possible monomer in a long list of suitable candidates for polyion segments. Applicants assert the reference primarily focuses on block or graft copolymers and does not disclose or suggest the use of a copolymer where DMAEMA makes up more than 75% of the monomers. Applicants assert that paragraph 75 of the reference specifically describes the polymers as having at least one polyion segment and one nonionic water-soluble segment.
Second, Applicants assert Zanata was cited for support but does not suggest using DMAEMA at such high concentrations or for the medical treatment uses recited in the amended claims.
Third, Applicants assert that because neither Kabanov et al and Zanata teaches or suggests the specific polymer architecture, monomer ratios, or medical uses now required by amended claim 12, the claimed combination is non-obvious over the cited references.
First, respectfully, this argument is not persuasive. While Kabanov et al may list N,N-dimethyl amino ethyl methacrylate (i.e., DMAEMA) in a list with other suitable polymers, a reference may be relied upon for all it teaches, even non-preferred embodiments. Here, Kabanov et al teach complexes comprising a polymer and a proteinaceous agent, wherein the polymer may be a homopolymer, wherein the homopolymer may have a net negative or positive charge, and suitable polymers include N,N-dimethyl amino ethyl methacrylate. While the examiner recognizes that paragraph 75 of Kabanov et al teaches an embodiment comprising at least one polyion segment and one nonionic water-soluble segment, this appears to just be a preferred embodiment, where the immediately preceding paragraph teaches homopolymers are suitable. The reference is not limited to the preferred embodiments.
Second, respectfully, this argument is not persuasive. Zanata was only cited as an evidentiary reference to show that poly(N,N-dimethylaminoethyl methacrylate) has a pKa between 7 and 7.5, not for teaching the use of DMAEMA at high concentrations or for medical treatments.
Third, respectfully, this argument is not persuasive. As discussed above, it appears that Kabanov et al teach and make obvious a complex comprising the homopolymer DMAEMA and a proteinaceous agent for medical applications, which appears to make obvious the claimed structure. Regarding the monomer ratios, where the complex comprises a homopolymer of DMAEMA, it appears DMAEMA is the only monomer that makes up the polymer, and therefore reads on having a molar ratio of N,N dimethyl amino ethyl methacrylate to a different repetitive unit of formula (I) of greater than 75%, which in this case appears to be 100%. Regarding the medical uses, where the complex made obvious above is administered to a subject to treat the subject for medical applications, it appears the method of medical treatment as instantly claimed is met.
Claims 20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Kabanov et al (US 20190111109 A1), as applied to claims 12, 15, 19, 22-25, 27, and 28 above, and further in view of Wilson et al (ACS Nano, 2013, 7, 5, pp. 3912-3925, cited on IDS dated 04/09/2023).
Kabanov et al are discussed above but do not teach wherein the proteinaceous agent is an antigenic peptide for vaccination, nor wherein the complex further comprises an adjuvant to enhance the immune response towards the antigenic peptide.
Wilson et al are discussed above and are repeated here for convenience. Wilson et al teach pH responsive nanoparticle vaccines where it was known to formulate polymeric complexes comprising DMAEMA (i.e., N,N-dimethyl amino ethyl methacrylate) for the co-delivery of proteinaceous antigens and immunostimulatory oligonucleotides (abs). Dual delivery of proteinaceous antigens and immunostimulatory oligonucleotides from the polymer complexes were known to significantly increase immune response (abs). In a particular embodiment, DMAEMA as the primary component (97%) (pg. 3913).
Regarding claims 20 and 21, the examiner notes that while the working embodiments are directed to delivery agents to the central nervous system, the reference more broadly teaches administering an active agent, in particular a proteinaceous active agent, from polymeric complexes for medical treatments. Accordingly, it would have been obvious to modify the complex in the method made obvious above, by selecting from other known protein based therapeutic agent that are suitable for polymeric complexes for administering to a subject for medical treatment, such as proteinaceous antigens, as taught by Wilson et al. Additionally, it would have been obvious to further include an oligonucleotide adjuvant, where the dual delivery of proteinaceous antigens and oligonucleotide adjuvant from polymeric complexes comprising N,N-dimethyl amino ethyl methacrylate were known to significantly increase immune response.
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Kabanov et al (US 20190111109 A1), as applied to claims 12, 15, 19, 22-25, 27, and 28 above, and further in view of Pippa et al (J Polym Res, 2018, 25: 117, pp. 1-9, cited on IDS dated 04/09/2023).
Kabanov et al are discussed above but do not specifically teach alginate.
Pippa et al teach it was known to encapsulate PDMAEMA polymers in alginate beads for use in gastric fluid (abs).
It would have been to encapsulate the complex in the method made obvious by Kabanov et al with other known encapsulating agents suitable for PDMAEMA polymers in gastric environments, such as alginate, as taught by Pippa et al.
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 JOSHUA A ATKINSON whose telephone number is (571)270-0877. The examiner can normally be reached M-F: 9:00 AM - 5:00 PM + Flex.
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/JOSHUA A ATKINSON/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612