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 .
Application Status
The action is written in response to applicant’s correspondence received on 6/11/2026. Claims 1, 3-18, and 20 are currently pending in the instant application.
Priority
The instant application claims foreign priority to EP21154745.0 with an effective filing date of 2/2/2021. The Certified Copy of Foreign Priority was filed on 8/2/2023 and has been acknowledged.
Election/Restriction
Applicant’s election of the invention of group I (Claims 1, 3-18), drawn to a method of eliciting an immune response in a subject by sole administration of an adjuvant, wherein the adjuvant is associated with one or more populations of polymersome, without traverse, in the reply filed on 6/11/2026 is acknowledged.
Claim 20 is withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable or generic linking claim.
Applicants elect the following species:
1) class B for the class of CpG oligonucleotide recited in claim 5,
2) SEQ ID NO: 62 for the sequence of said CpG oligonucleotide,
3) deblock (A-B-A) structure for the copolymer recited in claims 16 and 17, and
4) poly(butadiene)-poly(ethylene oxide) (PB-PEO) as the deblock copolymer recited in claim 17.
Claims 5-6, and 16-17 are withdrawn by the applicant.
Examiner has decided to examine claims 16 and 17 as applicant elects a deblock structure for the copolymer and PB-PEO as the deblock copolymer. There are no other claims directed towards these elected species.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Claims 1, 3-4, and 7-18 are currently under examination on the merits.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Hyperlinks can be found on paragraph [0011], [0082], [0083], [0084], [0119], [0226], and [0400].
The use of the term Revolution™ in paragraph 0449, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
Regarding sequence deficiency, applicant submits Fig. 31 which discloses a nucleotide sequence greater than 10 nucleotides in length. Looking to the specification for guidance, paragraph 0119 provides the brief description of the exemplary nucleotide sequence of CpG-A ODNs, however, does not provide a SEQ ID NO. Regardless if these sequences are exemplary, proper SEQ ID NOs are required for all nucleotide sequences greater than 10 nucleotides of length.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
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.
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.
Written Description
Claim 1, 3-4, and 7-18 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.
Breadth of the Claims
With regards to the breadth of the claims, the instant claim 1 broadly recites a method of eliciting an immune response in a subject by the sole administration of any adjuvant associated with any polymersome. Here, applicant defines the term “adjuvant” as a compound or substance capable of inducing, enhancing, or improving an immune response with or without an antigen. Though the applicant does not directly define a polymersome, one skilled in the art would apply the broadest interpretation would include any vesicles, such as nanoparticles, made up of polymer molecules, absent evidence to the contrary.
The instant claim 11 recites a method of eliciting an immune response, wherein the immune response comprises stimulating production of cytokines, specifically IL-6, and wherein IL-6 production is free of IL-12 production.
Species Described by Complete Structure or Reduction to Practice
With regards to the species described by complete structure or reduction to practice, the instant specification describes that any known adjuvant can be used in the present invention and that the types of adjuvant to be injected may be dependent on the types of antigen to be used for eliciting an immune response (see paragraph 0249). Applicant further specifies examples to include any adjuvant that may be of bacterial, viral, or fungi origin, nucleic acids such as CpG oligodeoxynucleotides, components derived from bacterial and mycobacterial cell wall such as components present in Sigma Adjuvant System or Freund’s adjuvants, or proteins such as KLH (see paragraph 0249).
In reduction to practice, applicant describes testing with polymersomes encapsulating CpG oligonucleotides (see Fig. 2) and SAS adjuvant (see Fig. 6). Figure 13 and 14 show the test of CpG ODN with an ACM polymersome and an OVA antigen for the treatment of cancer cells. Figure 28 shows ACM-CpG administration stimulates IL-6 production but is silent on where IL-6 production is free of IL-12 secretion.
Applicant provides experimental examples where B21, PDMS, PDMS with DSPE-PEG, and PLA-PEG were used as polymersomes for immunization (see Fig. 10). Applicant also describes that the polymersome can be a lipid polymer, or be comprised of a variety of polymers presented in paragraph 0266. However, given the large amount of different polymer combinations that can be used to generate a polymersome, the species presented by the applicant does not adequately describe the full breadth of the claimed invention.
State of the Prior Art
Looking to the prior art for guidance, Iannacone et al. (US 8.906,381 B2) describes a composition comprising a sole adjuvant, or an adjuvant with an antigen, wherein the adjuvant can be alum, MF59, cholera toxin, squalene, phosphate adjuvants, vitamin E, etc. (see column 16, line 37). Iannacone also describes gel-type adjuvants such as aluminum hydroxide, aluminum phosphate, calcium phosphate, etc. (see column 65, line 13). It is clear that Iannacone describes that the term “adjuvant” is immensely broad and encompasses both biological and non-biological molecules in order to elicit an immune response.
Iannacone also states a wide variety of polymers and methods for forming polymeric matrices are known in the art of drug delivery and provides numerous examples (see column 87, line 57). It is evidenced here that the formulation of a polymersome can encompass a large magnitude of combinations, where a few reduction to practices as described by the applicant cannot fully characterize the entire genus of polymersomes.
Taken together, given the broadness of the general term adjuvant and polymersomes, and the evidence provided by the instant specification, it is clear the instant specification fails to adequately describe the claimed invention in such a way to reasonably convey to one skilled in the relevant art that the instant co-inventors had possession of all the claimed inventions (i.e. a method of administering any adjuvant with any polymersome) and does not show how a method of IL-6 secretion would be free of IL-12 secretion, at the time the application was filed.
Scope of Enablement
Claims 1, 3-4, and 7-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method to elicit a non-specific immune response, does not reasonably provide enablement for a method eliciting a specific immune response wherein the method is a method of treatment and prophylactic method is against a variety of diseases listed in claim 14. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the specification coupled with information known in the art without undue experimentation (United States vs Telectronics., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based upon a single factor but rather is a conclusion reached by weighing many factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), and the most relevant Wands factors are indicated below:
As stated in MPEP §2164.01(a), “there are many factors to consider when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any experimentation is ‘undue’.” These factors include, but are not limited to:
The nature of the invention;
The breadth of the claims;
The state of the prior art;
The level of skill in the art;
The level of predictability in the art;
The amount of direction provided by the inventor;
The presence or absence of working examples;
The quantity of experimentation necessarily needed to make or use the invention based on the disclosure.
See In re Wands USPQ 2d 1400 (CAFC 1988).
Nature of the Invention
Claim 1 recites a method of eliciting an immune response in a subject by sole administration of an adjuvant associated with one or more population of polymersomes. Since applicant recites eliciting an immune response, the method is drawn to a therapeutic method or a method of treatment. This method of treatment, as defined by the applicant, can be a prophylactic method, wherein the administration of said adjuvant is for the prevention of a disease.
The Breadth of the Claims
Claim 1 is immensely broad. Applicant claims any adjuvant known the art as well as any polymersome, listing a wide variety of structural variation, that can be used to deliver said adjuvant. Furthermore, applicant does not specify whether the immune response is in response to a specific disease or non-specifically boosting immunity.
The State of the Prior Art and Level of Predictability
The method administers a sole adjuvant, as in an adjuvant without an antigen, to subject. The state of the art does support when administered alone, unmethylated CpG motifs trigger cells that express Toll-like receptor 9 (such as human plasmacytoid dendritic cells and B cell) to mount an innate immune response characterized by the production of Th1 and proinflammatory cytokines, such as IL-6, as evidenced by Bode et al. (CpG DNA as a vaccine adjuvant, Expert Rev Vaccines, Volume 10, Issue 4, pgs. 499-511, published 2011). Bode also teaches that when used as a vaccine adjuvants, CpG ODNs improve the function of professional antigen-presenting cells and boost the generation of humoral and cellular vaccine-specific immune response (see abstract of Bode). Klinman et al. (Repeated administration of synthetic oligodeoxynucleotides expressing CpG motifs provides long-term protection against bacterial infection, Infect Immun. Volume 67, Issue 11, pgs. 5658-5663, published 1999) does disclose protection against bacterial infection through multiple administration of a CpG ODN and that CpG ODN immunity involves a rapid innate immune response characterized by the production of immunostimulatory cytokines and polyreactive antibodies. This early response help limits a pathogen’s spread prior to the development of anti-specific sterilizing immunity (see discussion). It is clear that the effects of CpG in boosting innate immunity are known but often times, these effects are observed in conjunction with an antigen.
The state of the art further debates the efficacy of CpG ODNs as a standalone treatment. For example, Zhang et al. (CpG Oligodeoxynucleotides for Anticancer Monotherapy from Preclinical Stages to Clinical Trials, Pharmaceutics, Volume 14, Issue 1, Published 12/28/2021) recites “despite the wealth of preclinical research in CpG ODN antitumor immunity, none of the CpG ODN- derivatives have been approved as front-line anticancer treatments. Current CpG ODN monotherapies hardly trigger significant cellular immune responses, leading to low antitumor activities. Therefore, the clinical applications for CpG ODN against cancer are still limited to local administration in combination with chemotherapies or antibodies” (see discussion).
Clearly, the state of the art discloses CpG ODNs can be used as an adjuvant for specific immune response in combination with an antigen or standalone to boost immunity before the development of anti-specific sterilizing immunity, as discussed in Klinman. Therefore, as a standalone composition, it is uncertain if the sole administration of an adjuvant could treat and/or PREVENT the specific diseases as listed in claim 14.
Furthermore, it is still unclear whether CpG ODNs can be used to effectively treat diseases such as cancer, much less prevent cancer in the first place. Given that most artisans implement an antigen specific for a disease in conjunction with CpG ODNs, it is not predictable, unless without excessive experimentation, that the sole administration of CpG ODNs in order to broadly boost non-specific immunity would treat and/or prevent the wide array of diseases presented in claim 14 of the instant application.
The Presence or Absence of Working Examples
As a working example, applicant provides Fig. 13 and 14, which shows tumor growth curves after prophylactic and therapeutic vaccination of ACM OVA formulations, in vitro. Though the data does show a significant decrease of tumor cell volume 22 days after inoculation, this experiment was done in conjunction with OVA or chicken Ovalbumin (see paragraph 0015), which is a model antigen for cancer vaccines. Absent evidence to the contrary, applicant does not provide examples for the sole administration of an adjuvant, such as CpG oligonucleotides, can have a therapeutic effect on any of the claimed diseases of claim 14, such as preventing or treating cancer. Applicant merely shows in Fig. 28 where ACM-CpG adjuvants successfully induced cytokines production, which does support the boosting of the innate immune system, but that evidence does not fully support the prevention or treatment of all these diseases.
The Quantity of Undue Experimentation
The quantity of undue experimentation is very high. One skilled in the art would need to test all known adjuvants and known polymersome combinations, without an antigen, and administer them the various subjects. Furthermore, these subjects would need to be observed for the treatment and prevention of all diseases listed in claim 14. Applicant does not provide any working examples of a polymersome and adjuvant alone in the prevention of such diseases, only that ACM-CpG administration leads to increased IL-6 secretion.
Conclusion of 35 U.S.C. 112(a) Scope of Enablement Analysis
After applying the Wands factors analysis to claims 1, 3-4, and 7-13, and 15-18, taking into consideration the factors outlined above, it is concluded that the specification is not fully enabled for a method of eliciting a specific immune response in a subject by the sole administration of an adjuvant associated with a population of polymersomes. Absent evidence to the contrary, the state of the art uses antigens in conjunction with adjuvants in order to generate a specific immune response against a disease. The sole use of an adjuvant is linked to boosting overall non-specific innate immunity but does not support efficacy for any diseases. This is further exemplified by claim 14 as the state of the art is uncertain whether the sole administration of CpG ODNs can treat cancer, much less prevent it, as evidenced by Zhang et al. Furthermore, claim 14 recites a plethora of disease, many of which require specific targeted immunity with an antigen, which is not recited in the claimed invention. Absent objective evidence, the mere boosting of the innate immune system does not adequately encompass sufficient prevention of the diseases presented in claim 14.
Therefore, claims 1, 3-4, and 7-18 are rejected under 35 U.S.C. 112(a) for failing to disclose sufficient information to enable a person of skill in the art to use the invention commensurate in scope with these 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.
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.
Claims 3, ,4, 8, 11, 13-15, and 17 are 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.
Regarding claims 3, 4, 8, 11, 13, and 15, the term, “preferably” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 8, applicant recites “wherein the said adjuvant is independently selected from the group consisting of: (i) (ii)”. Applicant does not recite “and/or” between groups (i) and (ii). Therefore, it is unclear if both (i) CpG ODNs of Class B AND (ii) non-antigenic components derived from bacterial and mycobacterial cell walls make up the adjuvant in the recited claim, or if only one of the groups make up the adjuvant of the recited claim.
Regarding claim 11, applicant recites wherein said immune response comprises stimulating production and/or secretion of IL-6, preferably said production and/or secretion of IL-6 is predominant over production and/or secretion of IL-12. Predominant is relative terminology and looking to the specification for guidance, applicant does not define the degree of which IL-6 secretion is greater than the secretion of IL-12. Therefore, it is uncertain to what degree of predominance the applicant is reciting.
Regarding claims 3, 14, and 17 the phrase “for example” or “e.g.” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Interpretation
Regarding claim 1, examiner will interpret the claim 1 as a method of eliciting a non-specific immune response in a subject by the sole administration of an adjuvant. Furthermore, applicant recites preferred embodiments. Where the term “preferably” is used, examiner will interpret both options of having and not having said preferred embodiments in the prior art as meeting the claimed limitations.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3-4, 7, 10-16, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Iannacone et al. (US 8,906,381 B2, published 12/9/2014).
Regarding claim 1, Iannacone teaches compositions and systems for delivery of nanocarriers to cells of the immune system, wherein the synthetic nanocarriers are capable of eliciting an immune system response, wherein the immune response is enhanced specifically (with an antigen) or nonspecifically (without an antigen) (see abstract and column 2, line 35). Iannacone discloses the present invention provides methods of designing, manufacturing, and using such nanocarriers and pharmaceutical compositions thereof (see abstract). Iannacone teaches where in some embodiments, the immunostimulatory agent can CpG-containing immunostimulatory nucleic acids, which is non-antigenic (see column 16, line 19). Furthermore, Iannacone teaches the scaffold of the nanocarrier (and which the agents provided herein may be associated with or encapsulated by) can be composed of polymer and/or non-polymer molecules (see column 4, line 29).
Regarding claim 3, Iannacone teaches where inventive prophylactic and/or therapeutic protocols involve administering a therapeutically effective amount of one or more inventive vaccine nanocarriers to a subject such that an immune response is modulated (see column 25, line 25).
Regarding claim 4, Iannacone teaches where in some embodiments, immunostimulatory agents are CpG-containing immunostimulatory nucleic acids, a complement receptor agonist, or an adjuvant. In some embodiments, the TLR agonist is a TLR-9 agonist (see column 16, line 19). It is known to one with ordinary skill in the art, that class B CpG oligonucleotide are a specific agonist against TLR9. This is evidenced by Vollmer et al. (Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists, Advance Drug Delivery Review, volume 61, Issue 3, pgs. 195-204, published 3/28/2009).
Regarding claim 7, Iannacone teaches where a vaccine nanocarrier comprises at least one type of immunomodulatory agent that is associated with the exterior surface of the vaccine nanocarrier. In some embodiments, the association is covalent (see column 49, line 9).
Regarding claim 10, Iannacone teaches wherein the vaccine nanocarriers may transport one or more types of immunostimulatory agents which can help stimulate immune responses. In some embodiments, immunostimulatory agents boost immune responses by inducing the local release of mediators, such as cytokines from a variety of cell types (see column 20, line 58).
Regarding claim 11, Iannacone teaches where the cytokine is IL-6 (see column 14, line 54 and column 39, line 5). Iannacone does refer to IL-6 as a self-antigen, which is a normal substance in the body of an animal when an immune response is triggered (column 38, line 63).
Regarding claim 12, Iannacone teaches the composition is administered orally, parenterally, or via intramuscular injection (column 26, line 5).
Regarding claim 13, Iannacone discloses a method of administering a pharmaceutical composition comprising inventive compositions to a subject (e.g. human) in need thereof is provided (see column 25, line 40).
Regarding claim 15, Iannacone teaches where the present invention provides synthetic nanocarriers for modulating the immune system (see column 2, line 12). Iannacone further teaches where the nanocarriers of the composition provided herein have a mean geometric diameter that is greater than 50 nm but less than 500 nm (see column 5, line 25).
Regarding claim 16, Iannacone teaches where the polymer-antigen biconjugate system may be synthesized as a deblock copolymer (column 90, line 38). Though this system is drawn to a system of a polymer or polymersome with an antigen, it is described in previous embodiments of the invention, the synthetic nanocarriers comprise one or more of an immunostimulatory agent (column 2, line 21), wherein the agent can be CpG-containing immunostimulatory nucleic acid (see column 16, line 23).
Regarding claim 18, Iannacone teaches where in certain embodiments, the vaccine nanocarriers of the invention may be administered in amounts ranging from about 0.001 mg/kg to about 100mg/kg. Here, 0.001 mg/kg is converted to 1ug/kg, where the range encompasses about 7.5 ug to 12.5 ug per kg as recited by the instant claim.
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.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Iannacone et al. (US 8,906,381 B2, published 12/9/2014) in view of Komiya et al. (US 2018/0264105 A1, published 9/20/2018) and Mohsen et al. (Delivering adjuvants and antigens in separate nanoparticles eliminates the need of physical linkage for effective vaccination, Journal of Controlled Release, Volume 251, pgs. 92-100, published 4/10/2017).
Regarding claim 8, Iannacone teaches the method of claim 1, wherein a nanocarrier, made up of polymers, can solely comprise of an immunostimulatory agent on the surface of the nanocarrier, wherein the immunostimulatory agent can be CpG nucleic acids, specifically an agonist of TLR9 or class B CpG ODNs (see above).
Regarding claim 8, Iannacone teaches where the term adjuvant is intended to include any substance which is incorporated into or administered simultaneously with the conjugates of the invention and which nonspecifically potentiates the immune response in the subject.
Regarding claim 8, Iannacone does not teach where the CpG ODN is SEQ ID NO: 62 .
Regarding claim 8, Mohsen teaches where separate administration of encapsulated antigens and encapsulated CpG ODN adjuvants increase the half-life of the CpG adjuvant, reduce non-specific interactions with cells and proteins in vivo, reach the same draining lymph node, efficiently charge the same antigen-presenting cells, and eliminate the extra steps of physical linkage of the CpG adjuvant to the antigen (see abstract, introduction, and section 2.2).
Regarding claim 8, Komiya teaches CpG ODNs having immunostimulatory activity (see abstract). Komiya teaches SEQ ID NO: 14, which has 100% identity over the full length of SEQ ID NO: 62 of the instant application.
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the claimed invention, to have combined the teachings of Iannacone and Komiya to arrive at an adjuvant and a polymersome (or nanocarrier), wherein the adjuvant is a CpG ODN with the sequence of SEQ ID NO: 62, in order to elicit an immune response.
One would expect a reasonable chance of success as both Iannacone and Komiya teach where CpG ODNs are associated with either a nanocarrier or encapsulated in a lipofectin particle (see paragraph 0013 of Komiya) and administered to a subject to elicit an immune response. Furthermore, Mohsen provides further evidence that adjuvants can be encapsulated independently in a polymersome and administered.
One would be motivated to do so as Komiya teaches CPG ODNs are ligands of TLR9s and extremely efficient inducers of Th1 immunity or cytotoxic T-lymphocyte responses through TLR9 to stimulate the immune system (see paragraph 0004 of Komiya). Furthermore, this stimulation of the immune system is useful as Iannacone teaches said compositions can be used for prophylaxis and/or treatment of disease, disorders, or conditions modified by enhancing the immune response specifically or nonspecifically (see column 2, line 31 of Iannacone). One would be motivated to use the CpG ODN provided by Komiya with the polymersome composition of Iannacone to stimulate the immune system of a subject to treat or prevent diseases by boosting nonspecific immunity (compared to specific immunity with an antigen).
In view of the foregoing, claim 8 is rejected under U.S.C. 103(a)(1) as being prima facie obvious, before the effective filing date.
Claims 9 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Iannacone et al. (US 8,906,381 B2, published 12/9/2014) in view of Khan et al. (WO 2019/145475 A2, published 8/1/2019) Discher et al. (US 2005/0048110 A1, published 3/3/2005), and Mohsen et al. (Delivering adjuvants and antigens in separate nanoparticles eliminates the need of physical linkage for effective vaccination, Journal of Controlled Release, Volume 251, pgs. 92-100, published 4/10/2017).
Regarding claims 9 and 17, Iannacone teaches the delivery of polymer nanoparticles with an associated adjuvant, independent of any antigens, in order to stimulate a nonspecific immune response in a subject, as recited in claim 1. Mohsen teaches the motivation for the separate administration of an adjuvant, as described above.
Regarding claim 17, Iannacone teaches where in some embodiments, the present invention relates to the use of polymeric nanoparticle-antigen bioconjugate systems as a platform to induce the production of antibodies. Furthermore, the polymer-antigen bioconjugates system may be synthesized as a deblock, triblock, and/or multiblock copolymer (see column 90, line 29).
Regarding claims 9 and 17, Iannacone does not teach where the polymersome is oxidation-stable or where the said amphiphilic polymer is poly(butadiene)-poly(ethylene oxide) or PB-PEO deblock copolymer and comprises of a copolymer poly(N-vinylpyrrolidone)-b-PLA.
Regarding claim 9, Khan teaches a population of polymersomes which are oxidation-stable (see paragraph 0003) wherein oxidation-stable refers to a measure of polymersomes resistant to oxidation (0062).
Regarding claim17, Khan teaches amphiphilic polymers for the delivery of an encapsulated antigen in order to invoke an immune response (see paragraph 0009). Khan also teaches where the copolymer can be a PB-PEO deblock (see paragraph 0197) and wherein said amphiphilic polymer comprises a copolymer poly(N-vinylpyrrolidone)-b-PLA (see paragraph 0210).
Khan does not teach wherein a sole adjuvant is associated with a polymersome and administered to a subject to facilitate an immune response, instead teaching an antigen-polymersome composition that can further comprise an adjuvant.
Regarding claim 17, Discher teaches biocompatible vesicles, semi-permeable, thin-walled encapsulating membranes which comprise one or more synthetic super-amphiphile molecules (see abstract). Discher further teaches the present invention provides polymeromes which encapsulate one or more compositions, such as an adjuvant (0022).
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the claimed invention, to have combined the teachings of Iannacone, Khan, Mohsen, and Discher, to arrive at a method of administering a sole adjuvant associated with a population of polymersomes, wherein the polymersome is oxidation-stable and the amphiphilic polymer is PB-PEO deblock.
One would expect a reasonable chance of success as all the combined arts teach encapsulating or associating an adjuvant with a synthetic nanoparticle, such as a polymersome, in order to elicit an immune response. Iannacone, Discher, and Mohsen teach where the adjuvant that can be encapsulated is specifically CpG ODN, and Iannacone teaches where the CpG oligonucleotide of class B (a TLR9 agonist). Furthermore, Khan teaches the structural composition of a polymersome deblock PB-PEO with a copolymer to deliver compositions to modify immune response.
One would be motivated to combine these arts in order to provide a CpG adjuvant as a prophylaxis and/or treatment of a variety of infectious diseases, disorders, and/or conditions by eliciting an immune response, as taught by Iannacone (column 24, line 66). Furthermore, Mohsen provides motivation on the sole administration of an adjuvant as Mohsen teaches where separate administration of encapsulated antigens and encapsulated CpG ODN adjuvants increase the half-life of the CpG adjuvant, reduce non-specific interactions with cells and proteins in vivo, reach the same draining lymph node, efficiently charge the same antigen-presenting cells, and eliminate the extra steps of physical linkage of the CpG adjuvant to the antigen (see abstract, introduction, and section 2.2). This is further motivated by Iannacone wherein adjuvant administration without an antigen can lead to a nonspecific immune response (see column 65, line 30). One would be further motivated to use an oxidation-stable deblock-copolymer, such as PB-PEO, as oxidation-stable polymersomes prevent the premature release or loss of encapsulated antigen under oxidative conditions, as taught by Khan (see paragraph 0062) and a copolymer such as poly(N-vinylpyrrolidone)-b-PLA as these can serve as stabilizers (see paragraph 0166). Though Khan teaches the use of polymersomes for antigens, is it obvious that the teachings of Mohsen show that antigens and adjuvants can both be encompassed by polymersomes for the purpose of enhancing stability.
In view of the foregoing, claims 9 and 17 are rejected under 35 U.S.C. 103 as being prima facie obvious before the effective filing day.
Conclusion
No claim are allowed.
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/D.T.Y./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
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