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 .
Claims Status
Claims 1-10, 12, 15-21, 37, 42, and 43 are pending. Claims 12 and 21 are withdrawn from consideration. Claims 1-10, 15-20, 37, 42, and 43 are under examination on the merits.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-10, 12, 15-20, 37, and 42-43, and the required species, a respiratory viral infection caused by a coronavirus, and SARS-CoV-2 specifically, in the reply filed on 7/22/2026 is acknowledged.
Claim 12 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, and claim 21 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/22/2026.
Claims 1-10, 15-20, 37, 42, and 43 are under examination on the merits.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 6/6/2024, 10/25/2024, and 7/22/2026 are in compliance with 37 CFR 1.97. Accordingly, the references listed in the IDSs are being considered by the examiner.
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 Objections
Claims 1 and 37 are objected to because of the following informalities: the claims recite “a method of treating, preventing, and/or inhibiting one or more of the symptoms of a respiratory viral infection in a subject, and/or reducing morbidity and/or mortality of the respiratory viral infection in the subject, and/or inducing an innate immune response in mucosa of the subject, and/or generating mucosal secretory IgA antibodies and/or neutralizing serum IgG antibodies in the subject, and/or vaccinating the subject against the respiratory viral infection” in lines 1-6. To put the claim in better form, the alternative method goals should be placed in a list format. Appropriate correction is required.
Claims 1 & 4 are objected to because of the following informalities: the recite “generates [..] neutralizes the serum IgG antibodies” on lines 15-16 and 2-3, respectively, which appears to be a typographical mistake for “neutralizing serum IgG antibodies”. Appropriate correction is required.
Claims 37 and 42 are objected to because they depend on claim 21, which is withdrawn from consideration. The claims should be rewritten to incorporate the limitations of the withdrawn claim directly, rather than by dependance. Appropriate correction is required.
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.
Claims 1-10, 15-20, 37, and 42-43 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.
The term “about” in claims 1, 15-19, and 21 (which is withdrawn but claims 37 and 42 depend upon) is a relative term which renders the claims indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In claim 1, the term “about” renders indefinite the GC molecular weight (as in claims 16, 17, 19, & 21), degree of glycation of free amino groups (as in claims 18, 19, & 21), and degree of deacetylation of a chitin parent of the GC polymer (as in claim 15, 19, & 21).
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.
Scope of Enablement
Claims 1-10, 15-20, 37, 42, and 43 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 of preventing symptoms of a respiratory viral infection in a subject or generating neutralizing serum IgG antibodies in a subject with an antigen that has been shown to generate neutralizing IgG, does not reasonably provide enablement for similar methods using generic antigens, or no specific antigen at all. 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 or use the invention commensurate in scope with these claims.
The breadth of the claims is found in claims 1 and 37.
The nature of the invention is a method of treating, preventing and/or inhibiting one or more of the symptoms of a respiratory viral infection in a subject, and/or reducing morbidity and/or mortality of the respiratory viral infection in the subject, and/or inducing an innate immune response in mucosa of the subject, and/or generating mucosal secretory IgA antibodies and/or neutralizing serum IgG antibodies in the subject, and/or vaccinating the subject against the respiratory viral infection, the method comprising administering to the subject a therapeutically effective amount of a glycated chitosan (GC) polymer, wherein the GC polymer has a molecular weight ranging from about 10,000 Daltons to about 500,000 Daltons, a degree of glycation of free amino groups ranging from about one tenth of one percent to about 30 percent, and a degree of deacetylation of a chitin parent of the GC polymer ranging from about 70 percent to about 99 percent, wherein the administering to the subject treats, prevents and/or inhibits the one or more of the symptoms of the respiratory viral infection in the subject, and/or reduces morbidity and/or mortality of the respiratory viral infection in the subject, and/or induces the innate immune response in mucosa of the subject, and/or generates the mucosal secretory IgA antibodies and/or neutralizes the serum IgG antibodies in the subject, and/or vaccinates the subject against the respiratory viral infection (claim 1).
The level of skill of one skilled in this art is high.
The specification teaches administration of GC polymer in combination with the S1 subunit of the spike protein and/or nucleocapsid protein to mice (Examples 1-2, 7, and 9), which exhibited SARS-CoV-2-specific antibodies. These teachings do not enable the full breadth of the claims because they do not demonstrate neutralizing antibodies are generated after administrating the claimed GC polymer and any, generic respiratory virus antigen (or no antigen at all, since claim 1 does not require a specific antigen in addition to the GC polymer). The examiner is interpreting “preventing [..] symptoms of a respiratory viral infection in a subject”, absent specific definition in the specification, to be the same as preventing the natural infection.
The state of the prior art is such that it is well established in the art that neutralizing antibodies against a virus are not generated against each and every epitope of a given viral polypeptide.
Reasonable guidance with respect to preventing any viral infection relies on quantitative analysis from defined populations that have been successfully pre-screened and are predisposed to particular types of viruses. The essential element towards the validation of a preventive therapeutic is the ability to test the drug on subjects monitored in advance of clinical infection and link those results with subsequent histological confirmation of the presence or absence of disease. This irrefutable link between antecedent drug and subsequent knowledge of the prevention of the disease is the essence of a valid preventive agent. Further, a preventive administration also must assume that the therapeutic will be safe and tolerable for anyone susceptible to the disease. Therefore, Applicant may provide data showing prevention in vivo.
As stated in Cross v. Iizuka, 753 F.2d 1040, 1050, 224 USPQ 739, 747 (Fed. Cir. 1985): [B]ased upon the relevant evidence as a whole, there is a reasonable correlation between the disclosed in vitro utility and an in vivo activity, and therefore a rigorous correlation is not necessary where the disclosure of pharmacological activity is reasonable based upon the probative evidence. (Citations omitted.) Therefore, in the absence of the in vivo data above, Applicant may also provide evidence of pharmacological activity that would reasonably correlate with prevention of infection.
In the case of virus vaccines, a reasonable nexus exists between neutralizing antibody generation and prevention of infection. Thus, a showing that an antigen within the recited immunogen scope can produce such antibodies would support enablement for use of said antigen in a vaccine and/or methods of preventing infection therewith of the virus comprising said antigen.
Burton (Nature Reviews Immunology, Vol. 2, Pg. 706-713, 2002) teaches neutralizing antibodies are crucial for vaccine-mediated protection against viral diseases (Abstract). Figure 1 divides antiviral activities of antibodies into two groups: activities against free virus and activities against infected cells. Actual block of infection (prevention of infection) is taught to be the role of neutralizing antibodies (Figure 1). Nonneutralizing antibodies thus cannot prevent infection, only treat an infection.
Adding to the unpredictability is the fact that not just any epitope of a target antigen/virus will lead to antibody generation, let alone that of neutralizing antibodies. Riddell (Journal of Virology, Vol. 74, No. 17, Pg. 8011-8017, 2000) at the abstract teaches patient sera reacts with some but not all B-cell epitopes on ORF7.1 protein. Thus, not just any epitope/antigen/immunogen will contribute to patient immunity against a virus. Sugiyama (Journal of Virology, Vol. 76, No. 4, Pg. 1691-1696, 2002) supports this by teaching in their abstract that even amongst known epitopes that lead to neutralizing antibodies in some species, another subject’s immune reaction will not necessarily generate antibodies against all said epitopes.
Seydoux (Immunity 53, 98-105, July 14, 2020) isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject 21 days after the onset of clinical disease, generated 45 S-specific monoclonal antibodies, three of which bound the receptor-binding domain (RBD; Abstract). Two antibodies neutralized SARS-CoV-2, and the most potent antibody bound the RBD and prevented binding to the ACE2 receptor, while the other bound outside the RBD; thus, most anti-S antibodies that were generated in this patient during the first weeks of COVID-19 infection were non-neutralizing and target epitopes outside the RBD (Abstract). Data are clearly required to calm the concerns of the prior art and make methods of viral infection prevention and vaccine products predictable.
Taken together, it is clear from the prior art that a PHOSITA cannot predict the preventative power of any immunogen. They must be shown data that supports such a conclusion. Without demonstration of neutralizing antibody production, for example, in the target population with the specific immunogen, no practitioner in this art would see any given immunogen as a functional, predictable prophylactic agent.
Thus, the state of the art recognized that it would be highly unpredictable that a generic respiratory viral antigen, or no viral antigen at all, would prevent symptoms of a respiratory virus infection or generate neutralizing serum IgG antibodies. One of skill in the art would neither expect nor predict the appropriate functioning of the methods as broadly as currently claimed.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by Burton, Riddell, Sugiyama, and Seydoux, the lack of guidance and direction provided by applicants, and the absence of working examples, undue experimentation would be required to practice the claimed methods with a reasonable expectation of success, absent a specific and detailed description in applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed methods are functional, commensurate in scope with the claimed invention.
Moreover, claims not containing elements critical or essential to the practice of the invention, such as methods lacking viral antigens known to be capable of generating neutralizing antibodies against a respiratory virus, are not enabled by the disclosure. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
Note that an enabling disclosure for the preparation and use of only a few analogs of a product does not enable all possible analogs where the characteristics of the analogs are unpredictable. See Amgen Inc. v. Chugai Pharmaceutical Co. Ltd. (18 USPQ 2d 1027 (CAFC 1991)).
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.
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 1-10, 15-20, 37, 42, and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Cho (PGPub US 20210275665 A1, filed 3/4/2021) in view of Hode, et al. (PGPub US20150018748A1, published 1/15/2015).
The claimed invention encompasses a method of treating, preventing and/or inhibiting one or more of the symptoms of a respiratory viral infection in a subject, and/or reducing morbidity and/or mortality of the respiratory viral infection in the subject, and/or inducing an innate immune response in mucosa of the subject, and/or generating mucosal secretory IgA antibodies and/or neutralizing serum IgG antibodies in the subject, and/or vaccinating the subject against the respiratory viral infection, the method comprising administering to the subject a therapeutically effective amount of a glycated chitosan (GC) polymer, wherein the GC polymer has a molecular weight ranging from about 10,000 Daltons to about 500,000 Daltons, a degree of glycation of free amino groups ranging from about one tenth of one percent to about 30 percent, and a degree of deacetylation of a chitin parent of the GC polymer ranging from about 70 percent to about 99 percent, wherein the administering to the subject treats, prevents and/or inhibits the one or more of the symptoms of the respiratory viral infection in the subject, and/or reduces morbidity and/or mortality of the respiratory viral infection in the subject, and/or induces the innate immune response in mucosa of the subject, and/or generates the mucosal secretory IgA antibodies and/or neutralizes the serum IgG antibodies in the subject, and/or vaccinates the subject against the respiratory viral infection (claim 1).
The Prior Art
Cho teaches immunogenic compositions to protect humans from disease caused by SARS-CoV-2 (para. [0003]), and include a subunit protein vaccine based on the RBD of Spike (S) glycoprotein of SARS-CoV-2 (para. [0006]). Cho also teaches the vaccines or immunogenic composition may comprise one or more adjuvants, which are compounds that enhance the effectiveness of the vaccine, providing enhanced immune response even after administration of only a single dose of the vaccine (paras. [0009] and [0034]). Cho specifically teaches that adjuvants have profound effects on kinetics of neutralizing antibody induction, total antibody titers, antibody avidity, antibody longevity and B-cell epitopes targeted by the immune system (para. [0235]). Cho also discloses a method of preventing or delaying the onset of SARS or of reducing at least one symptom of SARS in an animal, comprising the step of providing an effective amount of an immunogenic composition comprising the RBD of the SARS-CoV-2 spike protein, and a carrier to the animal (Cho, claims 1 and 13). Cho also discloses that its vaccines may be administered intranasally, intramuscularly, subcutaneously, or mucosally (para. [0143]), and that one may use nasal solutions or sprays (para. [0135]). Cho’s vaccines or immunogenic compositions may be administered in a manner compatible with the dosage formulation, and in such an amount as will be therapeutically effective and immunogenic (para. [0145]).
Cho further teaches that to examine anti-RBD antibody responses, ELISA was performed using pooled sera from mice immunized three times on weeks 0, 2, and 5, with groups of A) mock immunized, B) RBD only, without adjuvant, C) RBD with alhydrogel adjuvant, D) RBD with aluminum phosphate, and E) RBD with Zn-chitosan (paras. [0241-242]). Additionally, Cho teaches that neutralizing antibodies are the major immune correlates of protection against viral diseases, and after the third immunization, all three groups with adjuvanted RBD vaccines mounted strong neutralizing antibody responses (para. [0243]).
However, Cho does not teach a glycated chitosan polymer, or one that has a molecular weight ranging from about 10,000 Daltons to about 50,000 Daltons, a degree of glycation of free amino groups ranging from about one tenth of one percent to about 30 percent, and a degree of deacetylation of a chitin parent of the GC polymer ranging from about 70 percent to about 99 percent, or its use as an adjuvant in a method of vaccinating against SARS-CoV-2.
Hode teaches therapeutic compositions comprising chitosan-derived compositions used in connection for treating neoplasms and other medical disorders (Abstract; para. [0002]), and that glycated chitosan preparations have shown significant efficacy as immunoadjuvants (paras. [0005] and [0014]). Hode further discloses a specific GC with a molecular weight of approximately 250 kDa, degree of deacetylation of about 80%, and degree of glycation of the free amino groups on the chitosan is about 12.5% (Fig. 2; para. [0057]). Hode specifically discloses that formulations of glycated chitosan activate one or more components of the immune system, mediating desired therapeutic effects, including innate immunity, namely the phagocytic system including macrophages in the tissues, and other components (paras. [0167-0168]). Hode also teaches glycosylated chitosan polymers that have a molecular weight between about 50,000 Daltons to about 1,500,000 Daltons, and the degree of glycation of free amino groups of the chitosan polymer range from about one tenth of one percent to about thirty percent (Hode, claim 1).
It would have been obvious to one of ordinary skill in the art to modify the methods of vaccinating against SARS-CoV-2 disclosed by Cho to incorporate use of the glycated chitosan as an adjuvant.
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious).
Accordingly, it would have been obvious to combine the immunoadjuvant of glycated chitosan having a degree of glycation of free amino groups ranging from about 10,000 Daltons to about 500,000 Daltons, a degree of glycation of free amino groups ranging from about one tenth of one percent to about 30 percent, and a degree of deacetylation of a chitin parent of GC polymer ranging from about 70 percent to about 99 percent, as disclosed by Hode, with the methods of administering immunogenic vaccine compositions comprising a SARS-CoV-2 spike RBD and adjuvant disclosed by Cho (thereby rendering obvious claims 1, 5, and 37). It also would have been obvious to one of ordinary skill in the art to formulate and administer a therapeutically effective amount of the SARS-CoV-2 spike RBD and adjuvant, because Cho teaches vaccines or immunogenic compositions may be administered in a manner compatible with the dosage formulation, and in such an amount as will be therapeutically effective and immunogenic.
Claim 2, which requires the method reduces morbidity and/or mortality of the respiratory viral infection in the subject, is rendered obvious because Cho teaches a method of preventing or delaying the onset of SARS or of reducing at least one symptom of SARS in an animal. Similarly, claim 43 is rendered obvious because it requires the administering to the subject treats, prevents and/or inhibits one or more of the symptoms of the respiratory viral infection in the subject.
Claim 3, which requires the method to induce the innate immune response in mucosa of a subject, is rendered obvious because Hode specifically discloses that formulations of glycated chitosan activate one or more components of the immune system, mediating desired therapeutic effects, including innate immunity, namely the phagocytic system including macrophages in the tissues, and Cho teaches administration of vaccines or immunogenic compositions to the mucosa, including intranasally and mucosally.
Claim 4, which requires generation of neutralizing serum IgG antibodies in the subject, is rendered obvious because Cho teaches that after immunization with SARS-CoV-2 spike RBD and different adjuvants, all three groups with adjuvanted RBD vaccines mounted strong neutralizing antibody responses.
Claim 6, which requires the therapeutically effective amount of a GC polymer is administered intranasally, intramuscularly or subcutaneously is rendered obvious because Cho discloses vaccine administration by each of those routes. Similarly, claim 42 is rendered obvious because it requires the vaccine is administered intranasally.
Claims 7-10, which require the subject to be a mammal (claim 7), specifically a human (claim 8), the respiratory viral infection is caused by coronavirus (claim 9), or SARS-CoV-2 (claim 10), they are each rendered obvious because Cho teaches immunogenic compositions to protect humans from disease caused by SARS-CoV-2.
Claims 15-19, which require particular GC polymer degree of deacetylation of a chitin parent (claims 15 and 19, about 80%), molecular weight (claim 16, about 50 kDA to about 350 kDA; claim 17, about 100 kDA to about 300 kDa; and claim 19, about 250 kDa), and degree of glycation of free amino groups (claim 18, about two percent to about seven percent; and claim 19, about two percent to about five percent), are rendered obvious because Hode discloses GC polymers with these parameters and their use as immunoadjuvants.
Claim 20, which requires the therapeutically effective amount of the GC polymer is formulated as a nasal spray or nasal drops, is rendered obvious because Cho teaches formulation of its vaccines as nasal solutions or sprays.
One of ordinary skill in the art would have been motivated to vaccinate against SARS-CoV-2 infection, reduce the morbidity and/or mortality of SARS-CoV-2 infection in the subject, induce the innate immune response in mucosa of the subject, and generating neutralizing serum IgG antibodies in the subject. There would be a reasonable expectation of success because Cho teaches use of adjuvanted spike RBD vaccines and Hode teaches that glycated chitosan is an immunoadjuvant. Therefore, claims 1-10, 15-20, 37, 42, and 43 were prima facie obvious before the priority date of the instant invention.
Conclusion
No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEFFREY MARK SIFFORD whose telephone number is (571)272-7289. The examiner can normally be reached 8:30 a.m. - 5:30 p.m. ET with alternating Fridays off.
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/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
