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 .
Claim Status
Claims 1-20 are currently pending.
Claims 13-20 have been withdrawn.
Claims 1-12 are being examined in this application.
Election/Restrictions
Upon further consideration, the species election as set forth in the previous Restriction Requirement (mailed on 6/6/25) has been withdrawn.
Applicant's election with traverse of Group I (claims 1-12) in the reply filed on 8/6/25 is acknowledged. The traversal is on the ground(s) that the “search burden requirement of MPEP 803(I)(B) has not been met…” for the species election requirement. Applicants have not traversed the restriction among the different Group of inventions. This is not found persuasive because as stated above, the species election requirement has been withdrawn. However, it is noted that the “search burden” is not part of the restriction practice for 371 application, and it is not a criteria for lack of unity consideration. Applicants are directed to MPEP 1850 I for requirement of for unity of invention. In this case, as demonstrated in the Election/Restriction Requirement, the instant claim lack unity of invention as the common technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Wang (WO2004/033663; 4/22/2004; Cited in IDS filed 9/26/2022). Wang teaches administering to a subject oligosaccharide (or oligomannose) cluster to a subject to induce an immune response to generating antibody 2G12 (e.g. Abstract; Page 1; Claims 15+). Therefore, the inventions lack unity as demonstrated by showing the common technical feature(s) does not “define a contribution over the prior art” “a posterior.” See MPEP 1850. Thus, the restriction requirement among the different groups is maintained.
The requirement is still deemed proper and is therefore made FINAL.
Claims 13-20 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 8/6/25.
Priority
This application is filed under 35 U.S.C 371 of PCT/US21/17821 (filed on 02/12/2021), which claims priority to US provisional applications 63/009,045 (filed on 04/13/2020).
Information Disclosure Statement
The IDS filed on 9/26/22 and 6/21/24 have been considered. See the attached PTO 1449 forms.
Claim Rejections - 35 USC § 112
112(a) Rejection(s)
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 Rejection
Claims 1-12 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.
The instant claims recite a method of vaccinating a subject against any viral pathogen using any glycoconjugate that are based on any oligomannose. The instant claims encompass any glycoconjugate, which give the broadest reasonable interpretation to mean any carbohydrate containing molecules that can mimic oligomannose immunogenicity in any viral pathogen and/or different viral pathogens. No structural and/or functional limitations are provided for the claimed genus of glycoconjugate that can be successfully used as a vaccine for any viral pathogen.
To satisfy the written description requirement, applicants may convey reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention.
Applicants may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. See, e.g., Vas-Cath, 935 F.2d at 1565, 19 USPQ2d at 1118.
The written description requirement of 35 U.SC. 112 exists independently of enablement requirement, and the requirement applies whether or not the case involves questions of priority. The requirement applies to all inventions and includes chemical inventions. The fact that the patent is directed to method entailing use of compounds, rather than to compounds per se, does not remove patentee’s obligation to provide a description of the compound sufficient to distinguish infringing methods from non-infringing methods. See Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ 2d 1886, 1890-93 (Fed. Cir. 2004).
With regard to the description requirement, applicants’ attention is invited to consider the decision of the Court of Appeals for the Federal Circuit, which holds that a “written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula [or] chemical name,’ of the claimed subject matter sufficient to distinguish it form other materials.” University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1405 (1997), quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (bracketed material in original) [The claims at issue in University of California v. Eli Lilly defined the invention by function of the claimed DNA (encoding insulin)].
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species or by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F. 3d at 1568, 43 USPQ2d at 1406.
The instant claims seem to encompass any glycoconjugate, any oligomannose, and any viral pathogen. Claim 1 reads on methods of using any glycoconjugate, which give the broadest reasonable interpretation to mean any carbohydrate containing molecules that can mimic oligomannose immunogenicity in any viral pathogen and/or different viral pathogens. Neither the instant specification nor the claims have demonstrated common structure and/or function for the claimed genus of (oligomannose based) glycoconjugate that are capable eliciting immunogenicity against a specific viral pathogen and/or plurality of different viral pathogen. In addition, no representative numbers of species for each claimed genus are provided to show possession of the claimed genus of vaccines.
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. (see MPEP 2163 II). In this case, the instant specification is generic for screening or designing oligomannose based epitopes, and testing these glycoconjugates in mice models. There is no core structure disclosed nor representative number of species of the glycoconjugates that can predictably used to for generate or elicit bnAb in any subject for any viral pathogen. There are no working examples of using any of the glyco-epitope to elicit immunogenicity in a subject against any viral pathogen, and/or showing successful prevention or inhibition of any viral infection using any of the glyco-epitope. It is also not known in the art that any glycoconjugate with any oligomannose structure can successfully elicit immunogenicity for any viral pathogen. For example, Bastida et al (Synthetic carbohydrate-based HIV-I vaccines. Drug Discovery Today: Technologies. Vol.35: 45-56; 2020), throughout the publication reviews carbohydrate-based HIV-I vaccine development. The reference lists numerous attempts using high mannose clusters that mimic 2G12 bnAb epitope (e.g. Figure 1). However, the reference states that none of these high mannose cluster vaccine candidates elicit effective immunogenicity despite their binding affinity to the 2G12 bnAb (p.48). The reference concludes that “despite their high affinity to the corresponding bnAbs, the induction of an effective HIV-I protective response still remains elusive.” Thus, generating or using glycoconjugate such as high mannose clusters to immunize against viral pathogens such as HIV-I is highly unpredictable as demonstrated by Bastida.
Therefore, applicants are not in possession of the claimed genus of glycoconjugate vaccine that can elicit immunogenicity against any viral pathogen. Applicant’s claimed scope represents only an invitation to experiment regarding possible oligomannose structure that might be identified through screening assay that may produce binding antibodies, but do not necessarily elicit the desired immunogenicity.
Scope of Enablement Rejection
Claims 1-12 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for using certain types of high-mannose oligosaccharide to elicit HIV-1 bnAbs 2G12 for certain degree of vaccination, does not reasonably provide enablement for using any other glycoconjugate (with any oligomannose) to elicit immunogenicity for any other virus as well as not enabled for “prevention from infection from… different viral pathogens” (as recited in claim 12). 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.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. §112, first paragraph, have been described In re Wands, 8 USPQ2d 1400(1988). They are:
1. The breadth of the claims;
2. The nature of the invention;
3. The state of the prior art;
4. The predictability or lack thereof in the art
5. The level of skill in the art;
6. The amount of direction or guidance present;
7. The presence or absence of working examples;
8. The quantity of experimentation needed.
The breadth of the claims / The nature of the invention
The breadth of the claims seems to encompass any glycoconjugate, any oligomannose, and any viral pathogen. Claim 1 reads on methods of using any glycoconjugate, which give the broadest reasonable interpretation to mean any carbohydrate containing molecules that can mimic oligomannose immunogenicity in any viral pathogen and/or different viral pathogens. Claim 12 reads on a method of “preventing” any viral infection using a glycoconjugate as the vaccine. No structural and/or functional limitations are provided for the claimed genus of glycoconjugate that can be successfully used as a vaccine for any viral pathogen.
The nature of the invention in claim 1 is a method of vaccinating a subject against any viral pathogen using a glycoconjugate. The nature of the invention in claim 12 is a method of preventing any viral pathogen infection using a glycoconjugate.
The state of the prior art / The predictability or lack thereof in the art
Generating and using glycoconjugate (high mannose cluster) vaccines to elicit immunogenicity against any viral pathogen in a subject is highly unpredictable. First, not all “viral pathogens” would exhibit high mannose clusters on its surface (viral envelope). That is oligomannose epitopes would not elicit immunogenicity for any “viral pathogen.” Second, although it has been known and widely studied that the high mannose clusters on the HIV-1 envelope are target for vaccine development, there is yet to be an effective vaccine based on the oligomannose cluster on the viral envelope. For example, Bastida et al (Synthetic carbohydrate-based HIV-I vaccines. Drug Discovery Today: Technologies. Vol.35: 45-56; 2020), throughout the publication reviews carbohydrate-based HIV-I vaccine development. The reference lists numerous attempts using high mannose clusters that mimic 2G12 bnAb epitope (e.g. Figure 1). However, the reference states that none of these high mannose cluster vaccine candidates elicit effective immunogenicity despite their binding affinity to the 2G12 bnAb (p.48). The reference concludes that “despite their high affinity to the corresponding bnAbs, the induction of an effective HIV-I protective response still remains elusive.” Thus, generating or using glycoconjugate such as high mannose clusters to immunize against viral pathogens such as HIV-I is highly unpredictable as demonstrated by Bastida.
The above discussion illustrate challenges with developing bnAbs for HIV-I. Currently, there is no successful glycoconjugate vaccine for HIV-I. Although there are numerous research efforts, there are no predictable methods or solutions that would allow successful generation of any glycoconjugate for any viral pathogen.
The level of one of ordinary skill
The level of skill would be high, most likely at the Ph.D. level.
The amount of direction or guidance present / The presence or absence of working examples
The only guidance present in the instant specification is generic for screening or designing oligomannose based epitopes, and testing these glycoconjugates in mice models. There is no guidance for generating a working bnAb for any specific viral pathogen and/or generating a oligomannose based vaccine for eliciting specific immunogenicity against any specific viral or plurality of viral pathogens.
The only presence of a working example is screening various oligomannose based glyco-epitopes and isolating anti-oligomannose antibodies from mice models. There are no working examples of using any of the glyco-epitope to elicit immunogenicity in a subject against any viral pathogen, and/or showing successful prevention or inhibition of any viral infection using any of the glyco-epitope.
The quantity of experimentation needed
Due to the unpredictabilities of using or making glycoconjugate to vaccinate or generate immunogenicity against any viral pathogen, undue experimentation would be required. The art has not demonstrated that high mannose based glyco-epitopes can predictably and successfully be used as a vaccine against any viral pathogen such as HIV-I and SARS-CoV-2. Because the instant specification only provides generic guidance and prophetic examples of generating possible glycoconjugate vaccine for viral pathogens, undue experimentation would be required to practice claimed method of vaccination using oligomannose based glycol-epitopes.
Conclusion
Therefore based on the evidences as a whole regarding each of the above factors (e.g. factors 1-8), the specification, at the time the application was filed, does not satisfy the enablement requirement for the instant claimed method.
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.
Wang
Claims 1-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang (WO 2004/033663; 4/22/2004; cited in IDS) as evidenced by Scanlan et al (Journal of Virology. Vol. 76(14): 7306-7321; 2002).
The instant claims recite “A method, comprising: administering an immunogenic vaccine composition to a subject, the immunogenic vaccine composition comprising a glycoconjugate; and in response to the immunogenic vaccine composition, inducing production of anti- oligomannose antibodies in the subject and thereby eliciting an immune response to a viral pathogen in the subject, wherein the anti-oligomannose antibodies are configured to elicit an immune response to a plurality of different viral pathogens including the viral pathogen.”
Wang, throughout the publication, teach carbohydrate-based synthetic vaccine including high-mannose oligosaccharide cluster for HIV (e.g. Abstract).
For claim 1, … administering an immunogenic vaccine composition to a subject, the immunogenic vaccine composition comprising a glycoconjugate…
Wang teaches HIV vaccine comprising high mannose type oligosaccharide cluster (e.g. p.1 lines 8+) and administering the oligomannose cluster to an animal (e.g. claim 20+), which the high mannose type oligosaccharide cluster read on the glycoconjugate.
…in response to the immunogenic vaccine composition, inducing production of anti- oligomannose antibodies in the subject and thereby eliciting an immune response to a viral pathogen in the subject, wherein the anti-oligomannose antibodies are configured to elicit an immune response to a plurality of different viral pathogens including the viral pathogen.
The Wang reference teaches the oligomannose cluster “induce immune response for increasing production of 2G12…” (e.g. Abstract; p 1, lines 10+; claims 15+), which the 2G12 antibody is known as the “broadly neutralizing antibody” (bnAbs) (e.g. p.2) that is capable of binding to different isolates of HIV-1 as evidenced by Scanlan et al (e.g. p. 7306-7307, bridging para). That is the elicited immune response by the oligomannose cluster of Wang through increase in production of 2G12 would result in “immune response to a plurality of different viral pathogens…” as recited in the instant claim 1.
For claim 2, the recitation of the instant claim 2 is inherent property of the vaccine itself as evidenced by the instant specification. Since the reference teaches the same oligomannose vaccine, the method of the reference would necessarily result in the immune response as recited in claim 2.
For claim 3, the reference teaches the oligomannose cluster “induce immune response for increasing production of 2G12…” (e.g. Abstract; p 1, lines 10+; claims 15+), which the 2G12 antibody is known as the “broadly neutralizing antibody” (bnAbs) (e.g. p.2).
For claim 4, the reference teaches various methods of administering including injection of solutions (e.g. p. 13, ll.15+).
For claim 5, the reference teaches administering a second (or repeating) dosage of the high-mannose oligosaccharide (e.g. p.17, ll.10+).
For claim 6, the reference teaches the antibody recognition of terminal mannose (e.g. p.32, last para).
For claim 7, the reference teaches the antibody 2G12 recognize epitope such as Man9GlNac (e.g. p.32, ll. 16+; Figures 13, 15), which reads on side chain and/or internal chain of the glycoconjugate.
For claim 8, the reference teaches eliciting response to HIV-1 (e.g. p.2).
For claim 9, the reference teaches using a carrier protein (e.g. p.6, ll.10+; claim 19).
For claim 10, the reference teaches “screening assays” to identify oligomannose or test substance against high-mannose oligosaccharide complexes (e.g. p.18, 28+; p.26, ll. 20+).
For claim 11, the reference teaches generating and screening hybridoma cells to generate the mAbs. (e.g. pp. 17-18 bridging para).
For claim 12, The Wang reference teaches the oligomannose cluster “induce immune response for increasing production of 2G12…” (e.g. Abstract; p 1, lines 10+; claims 15+), which the 2G12 antibody is known as the “broadly neutralizing antibody” (bnAbs) (e.g. p.2) that is capable of binding to different isolates of HIV-1 as evidenced by Scanlan et al (e.g. p. 7306-7307, bridging para), and reads on the recitation of the instant claim 12.
Conclusion and Correspondence
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUE LIU whose telephone number is (571)272-5539. The examiner can normally be reached M-F 9-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor (director), Jennifer Michener can be reached at 571-272-1424. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616
Prosecution Insights