DETAILED ACTION
Replace/Supersede Previous Office Action
This Office action supersedes and replaces the Office action mailed 05/05/2026. The period for reply runs from the mailing date of the present Office action.
Disposition of Claims
Claims 1-33 are pending.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20240156958A1, Published 05/16/2024.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Of note, there is not an attorney of record on file due to a lack of an official power of attorney of record. While a customer number has been provided on the ADS submitted 11/01/2023, this is not the equivalent of a power of attorney or an authorization to act in a representative capacity. In order to expedite prosecution in the instant application, it is suggested that a power of attorney be filed as per MPEP §402 or MPEP §1807, or an Authorization to Act in a Representative Capacity be filed as per MPEP §403 in order for the Office to freely and openly discuss the merits of the case with the applicant's representative(s). Please refer to https://www.uspto.gov/about-us/contact-us if you have questions regarding the proper filing of a power of attorney.
This updated action maintains all objections/rejections noted in the previous action and includes an additional new 35 USC 102(a)(2) rejection. While the new rejection is made over art cited in the previous Office action as apparently being commonly owned, a statement on record is required to invoke the 35 U.S.C. 102(b)(2)(C) exception, and said new rejection is required to be made until said statement is of record. See MPEP §2154.02(c): “In order to comply with the rules, a statement is required regardless of any assignment information that may have been recorded in the assignment database maintained by the Office.”
The supporting search documents and references were presented in the previous Office action and are already part of the file wrapper and will not be included with this action.
Optional Authorization to Initiate Electronic Communications
The Applicant’s representative may wish to consider supplying a written authorization in response to this Office action to correspond with the Examiner via electronic mail (e-mail). This authorization is optional on the part of the Applicant’s representative, but it should be noted that the Examiner may not initiate nor respond to communications via electronic mail unless and until Applicant’s representative authorizes such communications in writing within the official record of the patent application. A sample authorization is available at MPEP § 502.03, part II. If Applicant’s representative chooses to provide this authorization, please ensure to include a valid e-mail address along with said authorization.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 03/16/2024 and 07/29/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements 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.
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.
See e.g. ¶[0288] “References” with “https://doi.org/10.1038/srep19234” and “https://doi.org/10.1038/s41541-019-0132-6”.
Claim Objections
Claims 1-7, 18-19, and 32-33 are objected to because of the following informalities: claims 1, 32, and 33 are drawn to one (singular) or more (plural) linear carbohydrate molecules, the “s” in molecules should be in parentheses to indicate the alternative (e.g. “…one or more linear carbohydrate molecule(s)”). Dependent claims should also be updated accordingly (e.g. to read on “said one or more linear carbohydrate molecule(s)”). Appropriate correction is required.
Claims 11 and 25 are objected to because of the following informalities: it is suggested that “said plurality of immunogens” in claims 11 and 25 be amended to read on “said plurality of immunogen molecules” to place the claim in better form and in line with how other claims are drafted. Appropriate correction is required.
Claims 2, 4, 10-11, 20-24, and 30 are objected to because of the following informalities: it is suggested that “individually and independently” in claims 2, 4, and 10 and “independently and individually” in claims 11, 20-24, and 30 be deleted from the claims, as it is unnecessary in biological claim language that is not directly related to chemical structures (e.g. R groups and the like). Appropriate correction is required.
Claim 11 is objected to because of the following informalities: it is suggested that “comprising” at line 2 be amended to “consisting of” to place the Markush group in proper form. Appropriate correction is required.
Claim 12 is objected to because of the following informalities: it is suggested that “and” between “ethosomes and aquasomes” and “polymersomes and niosomes” be deleted and replaced with a comma to place the claim in better form. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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 and 32 and dependent claims 2-4, 7-17, and 20-31 thereof 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.
Claim 1 is drawn to a vaccine composition comprising a multivalent carrier covalently attached to one or more linear carbohydrate molecules and a plurality of immunogen molecules, said one or more linear carbohydrate molecules each attached to said multivalent carrier via a reducing end of said linear carbohydrate molecules. However, from the wording of the claim, it is unclear if the vaccine composition comprises: (A): 1) a multivalent carrier only attached to the one or more linear carbohydrate molecules and 2) a plurality of immunogen molecules; OR (B) 1) a multivalent carrier which is covalently attached to both the carbohydrate molecule AND the plurality of immunogen molecules. Another reasonable interpretation is that the carbohydrate molecule is attached to the immunogen, and then the carbohydrate is attached to the carrier at its reducing end. From the wording of the claim and the punctuation of the claim, there are multiple reasonable interpretations that are structurally two distinct compositions, and therefore the metes and bounds of the claim are unclear.
Claim 32 is rejected for similar reasoning.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 1 and 32 are rejected on the grounds of being indefinite. Claims 2-4, 7-17, and 20-31 are also rejected since they depend from claim 1, but do not remedy these deficiencies of claim 1.
Claims 1 and 32 and dependent claims 5-31 thereof 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.
Claim 1 is drawn to a vaccine composition comprising a multivalent carrier covalently attached to one or more linear carbohydrate molecules and a plurality of immunogen molecules, said one or more linear carbohydrate molecules each attached to said multivalent carrier via a reducing end of said linear carbohydrate molecules. However, from the wording of the claim, it is unclear if the “linear carbohydrate molecules” and the “plurality of immunogen molecules” are separate and distinct entities, or if they are the same. For instance, there are certain linear carbohydrate molecules that are immunogenic, particularly bacterial polysaccharides and certain complex glycans that form repetitive structures (e.g. from Streptococcus pneumoniae, Haemophilus influenzae type b, Neisseria meningitidis, Salmonella, Shigella, Bacillus anthracis, Clostridium difficile, etc.). While carbohydrates are generally known as T-cell-independent antigens that elicit a weaker immune response compared to proteins, many linear polysaccharide structures act as potent antigens, especially when they are large in molecular weight (e.g., >6,000 Daltons) or part of a glycoconjugate. It is suggested that limitations from dependent claims not included in this rejection be incorporated into the independent claim, or that the claim clearly distinguish that the “linear carbohydrate molecules” and the “immunogen molecules” are distinct, separate entities or are the same entities.
Claim 32 is rejected for similar reasoning.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 1 and 32 are rejected on the grounds of being indefinite. Claims 5-31 are also rejected since they depend from claim 1, but do not remedy these deficiencies of claim 1.
Claim 2 and dependent claims 3-4 thereof 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.
Claim 2 comprises an improper or an indefinite Markush grouping. First, Markush groups are expected to be closed, and the use of the open-ended transitional phrase “comprising” allows for the inclusion of additional, unrecited elements. Further, the language of “wherein said linear carbohydrate molecules are individually and independently selected” is awkward, as it phrases as although multiple molecules are each making a selection. Finally, the use of “and derivatives thereof” keeps the Markush group even further open, as said “derivatives thereof” is undefined and potentially encompasses an unlimited number of possibilities.
One suggestion is to amend claim 2 along the lines of:
“2. The vaccine composition of claim 1, wherein said one or more linear carbohydrate molecule(s) is/are selected from the group consisting of: chitin, partially deacylated chitin, chitosan, partially acylated chitosan, hyaluronic acid, keratin, keratin sulfate, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, and heparin.”
If Applicant is attempting to claim the breadth of “derivatives”, it is suggested the exact structural modifications that encompass said derivatives be claimed (e.g. “…wherein the derivative is [define said derivative structurally, such as a sugar alcohol, oxidized sugar, amino sugar, etc.].”)
Claims 3 and 4 are also included in this rejection for not only depending upon claim 2, but having similar issues as claim 2. Claim 3, for instance, still claims “derivative thereof” with respect to hyaluronic acid, but does not clarify what is, or what is not, a “derivative” of hyaluronic acid. Claim 4 does not clarify the metes and bounds of claim 2 and also uses the confusing “individually and independently selected” language. Claim 4 comprises a Markush group that fails to use an Oxford comma, so it is unclear if the limitation of “about 50,000 and about 110,000 Daltons” is meant to be a combination rather than an alternative selection. The use of “Daltons” in line 3 of the claim and then again in line 4 of the claim provides further ambiguity. Additionally, claim 1 notes that there may be “one or more” linear carbohydrate molecules, so with claim 4, it is unclear if this is an average if there are multiple heterologous linear carbohydrates, or if only one linear carbohydrate is used and said one carbohydrate has that singular weight. It is suggested claims 3 and 4 be amended along the lines of the following:
“3. The vaccine composition of claim 2, wherein said linear carbohydrate molecule is hyaluronic acid.”
“4. The vaccine composition of claim 2, wherein said one or more linear carbohydrate molecule(s) has an average molecular weight selected from the group consisting of about 6,000, about 10,000, about 20,000, about 30,000, about 40,000, about 50,000, and about 110,000 Daltons.”
For at least these reasons, claim 2 is rejected on the grounds of being indefinite. Claims 3-4 are also rejected for depending upon claim 2, but not clarifying the metes and bounds of claim 2.
Claim 7 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 7 is drawn to the vaccine composition of claim 1, wherein the number of said one or more linear carbohydrate molecule(s) and the number of said immunogen molecules is in a ratio from about 1:100 to about 100:1. However, the wording of the claim makes it unclear if the ratio is a total ratio (e.g. the total number of linear carbohydrate molecules vs. the total number of immunogen molecules) or if it is a general ratio (e.g. there is one species of linear carbohydrate in the composition (e.g. hyaluronic acid) and there are 100 different species of immunogens (e.g. SARS CoV-2 S protein, influenza A HA, influenza A NA, MERS CoV-2 S protein… to a total of 100 different species of immunogens.) From the guidance in the specification, it appears as though the former interpretation is correct, so the claim will be interpreted as reading upon:
“7. The vaccine composition of claim 1, wherein the total number of said one or more linear carbohydrate molecule(s) in the composition and the total number of said immunogen molecules in the composition is in a ratio from about 1:100 to about 100:1.”
For at least these reasons, claim 7 is rejected on the grounds of being indefinite.
Claims 8-9 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.
Claim 8 is drawn to the vaccine composition of claim 1, wherein said plurality of immunogen molecules comprises homologous immunogens. However, the limitation of “homologous immunogens” is unclear, because it is unclear as to what they are homologous to in comparison (e.g. the immunogens are all the same (e.g. all influenza A HA proteins of different H1 strains), the immunogens are from the same pathogen but are different proteins, as in the immunogens are all from influenza A virus (e.g. NA, HA, matrix, the immunogens all share some type of sequence or structural homology, etc.), or the immunogens are homologous to the multivalent carrier, or the immunogens are all of the same “type” (e.g. Coronaviridae spike (S) proteins from SARS CoV, SARS CoV-2, MERS CoV, etc.)
A similar issue with claim 9 is present, as it is unclear as to what the immunogens are heterologous to.
To clarify the scope of claims 8-9, it is suggested that the claims be amended to define the reference or benchmark as to which said immunogens should be compared.
As the metes and bounds of claims 8-9 are unclear, they are rejected for being indefinite.
Claim 11 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 11 recites the broad recitation “coronaviruses”, and the claim also recites “Middle East respiratory syndrome–related coronavirus (MERS-CoV)”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
For at least these reasons, claim 11 is rejected on the grounds of being indefinite.
Claim 14 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 14 provides the limitation of “wherein said virus-like particle is mutated Ap205 VLP.” However, it is unclear what is the “base” or “wild-type” Ap205 VLP and how said VLP would be “mutated” in comparison to said “base” VLP. The specification notes one example of a “mutated Ap205 VLP” as SpyCatcher-CP3 (¶[0081]), but there are other versions of Ap205 VLP in the art, so it is still unclear as to how to know if the Ap205 VLP in use is “mutated” or not.
As the metes and bounds of claim 14 are unclear, it is rejected on the grounds of being indefinite.
Claims 16-17 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.
Claim 16 is drawn to the vaccine composition of claim 15, wherein said self-assembling nanoparticle comprises a plurality of particle-forming proteins of 2-dehydro-3-deoxy-phosphogluconate (KDPG) aldolase or a variant thereof. Claim 17 is drawn to the vaccine composition of claim 16, wherein said self-assembling nanoparticle is selected from the group consisting of an i301 nanoparticle or a variant thereof, and a mi3 nanoparticle or a variant thereof. However, the use of “variant thereof” in claims 16 and 17 does not reasonably convey what is, and what is not, a “variant”, as no functional or structural language is tied to the “variant thereof” language. While “variant” is defined in the specification at ¶[0150], it is an extremely broad definition that does not make the metes and bounds of what is attempting to be claimed clear. One suggestion is to tie in both structural and functional limitations to the claims (e.g. “…comprises a plurality of particle-forming proteins of 2-dehydro-3-deoxy-phosphogluconate (KDPG) aldolase or a variant thereof having at least 80% identity to SEQ ID NO: X and retaining self-assembling activity.”)
For at least these reasons, the metes and bounds of claims 16-17 are unclear.
Claim 27 and dependent claims 28-31 thereof 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.
Claim 27 is drawn to the method of claim 26, wherein administering said vaccine composition comprises administering to the subject a first vaccine composition and administering to said subject a second vaccine composition. However, claim 26 is drawn to “wherein said vaccine composition is administered to the subject one or more times” and is tied to the vaccine of claim 1. The wording of the claim does not readily make the antecedent basis for the first and second vaccines recited in claim 27 clear – it is not clear that both have to be “vaccines of claim 1” or if only one of the two compositions listed must be a vaccine of claim 1. Additionally, the pendency of claim 27 is not clearly tied to the limitations of claim 26, as claim 26 states the composition can be administered only once, or multiple times; therefore, it is suggested claim 27 be amended to depend upon claim 20, and not claim 26. One suggestion is to amend claim 27 along the lines of:
“27. The method of claim 20, wherein administering said vaccine composition comprises administering to the subject:
(1) a first vaccine composition of claim 1, and
(2) a second vaccine composition of claim 1.”
For at least these reasons, the metes and bounds of claim 27 are unclear. Claims 28-31 are also rejected for depending upon claim 27, but not clarifying the issues regarding claim 27.
Claim 31 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.
The term “about simultaneously” in claim 31 is a relative term which renders the claim indefinite. The term “about simultaneously” 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. While the definition of “about” has been provided with respect to a measurable amount, “simultaneous” administration is not explicitly defined, so it is unclear how “about” would apply to “simultaneous” administration (e.g. if it would be prior to/following a certain amount of minutes, hours, days, etc. the administration of the second composition.)
For at least these reasons, the metes and bounds of claim 31 are unclear.
Claim Rejections - 35 USC § 112(d); Fourth Paragraph
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.
Claims 5-6 and 18-19 are 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 5 is drawn to the vaccine composition of claim 1, wherein said one or more linear carbohydrate molecule(s) and said immunogen molecules are each covalently attached via a respective peptide tag/binding site pair to said multivalent carrier. Claim 6 is drawn to the vaccine composition of claim 5, wherein there is an optional linker between said peptide tag and said one or more linear carbohydrate molecule(s). However, claim 1 provides that the said one or more linear carbohydrate molecules are each attached to said multivalent carrier via a reducing end of said linear carbohydrate molecules. Claims 18-19 have similar issues, as it does not clarify where the attachment of said linear carbohydrate molecule(s) occurs. Accordingly, the limitations of 5-6 and 18-19 make it unclear if this attachment must happen via the reducing end of said molecules, as a covalent attachment could be made via internal linkages of the carbohydrate. Therefore, the limitations of claim 5-6 and 18-19 appear to be broadening the scope of the claim upon which they depend.
One suggestion is to amend claims 5 and 18-19 along the lines of “…wherein said immunogen molecules are covalently attached to said multivalent carrier through a peptide tag/binding site pair, and wherein said one or more linear carbohydrate molecule(s) is/are attached to said multivalent carrier via its reducing end through a peptide tag/binding site pair.”
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 13 and dependent claim 14 thereof 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 13 depends upon claim 12, and notes that “said nanoparticle comprises a virus-like particle (VLP).[emphasis added]”. The use of the open-ended phrasing “comprises” creates ambiguity and broadens the scope upon which the claim depends, as the language of claim 13 allows for the VLP to be in combination with other items. While claim 12 allows for the use of combinations (e.g. “and combinations thereof”), claim 13 is specifically drawn to the nanoparticle, not a nanoparticle and any combination. One suggestion to clearly further limit the claims is to draft claim 13 along the lines of the following: “The vaccine composition of claim 12, wherein said nanoparticle is a virus-like particle (VLP).”
Or, alternatively, if a combination of VLP with another component is desired, it is suggested a new, dependent claim be presented that does not depend upon the Markush group of claim 12. (e.g. “The vaccine of claim 1, wherein said multivalent carrier comprises a VLP.”)
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 30 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 30 is drawn to the method of claim 27, where said administration of said first vaccine composition and said second vaccine composition are selected from the group consisting of enteral, oral, parenteral, topical, intranasal, intravaginal, intrarectal, intraocular, and intravitreal. However, claim 30 depends upon claim 20, which already claims all of these methods of delivery. 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 Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
“Multivalent carrier” is interpreted in light of the specification, noting that such a carrier “presents a plurality of binding partners providing a plurality of binding sites to attach the linear carbohydrate molecules and/or immunogens.”(¶[0014]).
“About” is interpreted in light of the specification to mean +/-10% a measurable amount (¶[0288]).
“peptide tag/binding site pair” is interpreted in light of the specification, such as proteins which are capable of spontaneous isopeptide bond formation may be expressed and/or synthesized as separate fragments, to give a peptide tag and a binding partner for the peptide tag, where the two fragments are capable of covalently reconstituting by isopeptide bond formation (e.g. SpyTag/SpyCatcher¶[0011-0013][0095]).
“Prevent” is interpreted in light of the specification (¶[0171]), in that “prevent” does “not require the 100% elimination of the possibility of an occurrence or an event, including disease transmission and retransmission. Rather, it denotes that the likelihood of the occurrence of the event has been reduced in the presence of the compound or method.”
Claim 1 is drawn to a vaccine composition comprising a multivalent carrier covalently attached to one or more linear carbohydrate molecule(s) and a plurality of immunogen molecules, said one or more linear carbohydrate molecules each attached to said multivalent carrier via a reducing end of said linear carbohydrate molecules.
Further limitations on the vaccine composition of claim 1 are wherein said one or more linear carbohydrate molecule(s) is/are selected from the group consisting of: chitin, partially deacylated chitin, chitosan, partially acylated chitosan, hyaluronic acid, keratin, keratin sulfate, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, and heparin (claim 2), wherein said linear carbohydrate molecule is hyaluronic acid (claim 3), wherein said one or more linear carbohydrate molecule(s) has an average molecular weight selected from the group consisting of about 6,000, about 10,000, about 20,000, about 30,000, about 40,000, about 50,000, and about 110,000 Daltons (claim 4); wherein said immunogen molecules are covalently attached to said multivalent carrier through a peptide tag/binding site pair, and wherein said one or more linear carbohydrate molecule(s) is/are attached to said multivalent carrier via its reducing end through a peptide tag/binding site pair (claim 5), wherein there is an optional linker between said peptide tag and said one or more linear carbohydrate molecule(s)(claim 6); wherein the total number of said one or more linear carbohydrate molecule(s) in the composition and the total number of said immunogen molecules in the composition is in a ratio from about 1:100 to about 100:1 (claim 7); wherein said plurality of immunogen molecules comprises homologous immunogens (claim 8); wherein said plurality of immunogen molecules comprises two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve heterologous immunogen molecules, each of which is different from one another (claim 9); wherein said plurality of immunogen molecules are derived from pathogens selected from the group consisting of protozoa, fungi, helminths, bacteria, and viruses (claim 10); wherein said plurality of immunogens are derived from pathogens selected from the group consisting of influenza viruses, rhinoviruses, human immunodeficiency viruses (HIV), respiratory syncytial virus (RSV), coronaviruses, dengue viruses, hepatitis viruses, West Nile virus, Middle East respiratory syndrome–related coronavirus (MERS-CoV), norovirus, Marburg viruses, Zika virus, orthopoxviruses, Togaviridae, Ebola virus, Borrelia, Babesia, methicillin-resistant Staphylococcus aureus (MRSA), Legionella, Chlamydia, Plasmodia, Streptococcus pneumoniae, Vibrio cholerae, Listeria, Clostridia, Salmonella, Bordetella, Enterococci, Treponemia, Amoeba, Neisseria, and Giardia (claim 11); wherein said multivalent carrier is selected from the group consisting of nanoparticles, nanotubes, nanowires, dendrimers, liposomes, ethosomes, aquasomes, polymersomes, niosomes, foams, hydrogels, cubosomes, quantum dots, exosomes, macrophages, and combinations thereof (claim 12), wherein said nanoparticle is a virus-like particle (VLP)(claim 13), wherein said virus-like particle is mutated Ap205 VLP (claim 14), wherein said nanoparticle is a self-assembling nanoparticle comprised of a plurality of particle-forming proteins (claim 15), wherein said self-assembling nanoparticle comprises a plurality of particle-forming proteins of 2-dehydro-3-deoxy-phosphogluconate (KDPG) aldolase or a variant thereof (claim 16), wherein said self-assembling nanoparticle is selected from the group consisting of an i301 nanoparticle or a variant thereof, and a mi3 nanoparticle or a variant thereof (claim 17), wherein said plurality of immunogen molecules are covalently attached to said particle-forming proteins of said self-assembling nanoparticle, and wherein said one or more linear carbohydrate molecule(s) is/are covalently attached via its reducing end to said particle-forming proteins of said self-assembling nanoparticle (claim 18), wherein said plurality of immunogen molecules are covalently attached through a SpyTag/SpyCatcher binding pair to said particle-forming proteins of said self-assembling nanoparticle, and wherein said one or more linear carbohydrate molecule(s) is/are covalently attached via its reducing end through a SpyTag/SpyCatcher binding pair to said particle-forming proteins of said self-assembling nanoparticle (claim 19)
Claim 20 is drawn to a method of stimulating an immune response in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of the vaccine composition of claim 1, wherein said vaccine composition administration is selected from the group consisting of enteral, oral, parenteral, topical, intranasal, intravaginal, intrarectal, intraocular, and intravitreal, thereby stimulating an immune response in the subject.
Further limitations on the method of claim 20 are wherein administering said vaccine composition induces neutralizing and cross-reactive neutralizing responses against additional immunogens different from said immunogens in said plurality of immunogens (claim 25); wherein said vaccine composition is administered to the subject one or more times (claim 26); wherein administering said vaccine composition comprises administering to the subject a first vaccine composition of claim 1 and administering to said subject a second vaccine composition of claim 1 (claim 27), wherein said immunogen molecules from said plurality of immunogen molecules in said first vaccine composition and said second vaccine composition are the same (claim 28) or are different (claim 29), where said administration of said first vaccine composition and said second vaccine composition are selected from the group consisting of enteral, oral, parenteral, topical, intranasal, intravaginal, intrarectal, intraocular, and intravitreal (claim 30), and wherein administering to the subject said second vaccine composition occurs simultaneously, two, three, four, five, six, seven, eight weeks, 10 weeks, 12 weeks, 16 weeks, 20 weeks, 24 weeks, 28 weeks, 6 months, 1 year, 5 years, or 10 years, after administering to said subject said first vaccine composition (claim 31).
Claim 21 is drawn to a method for treating or preventing an infection in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of the vaccine composition of claim 1, wherein said vaccine composition administration is selected from the group consisting of enteral, oral, parenteral, topical, intranasal, intravaginal, intrarectal, intraocular, and intravitreal, thereby treating or preventing the infection in the subject.
Claim 22 is drawn to a method for treating an infection in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of the vaccine composition of claim 1, wherein said vaccine composition administration is selected from the group consisting of enteral, oral, parenteral, topical, intranasal, intravaginal, intrarectal, intraocular, and intravitreal, thereby improving the survival rate in the subject.
Claim 23 is drawn to a method for treating an infection in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of the vaccine composition of claim 1 intranasal, intravaginal, intrarectal, intraocular, and intravitreal, thereby reducing the infectivity in the subject.
Claim 24 is drawn to a method of treating or preventing a disease or disorder caused by an infection in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of the vaccine composition of claim 1, wherein said vaccine composition administration is selected from the group consisting of enteral, oral, parenteral, topical, intranasal, intravaginal, intrarectal, intraocular, and intravitreal, thereby treating or preventing the disease or disorder caused by the infection in the subject.
Claim 32 is drawn to a kit, comprising a multivalent carrier covalently attached to one or more linear carbohydrate molecule(s) and a plurality of immunogen molecules.
Claim 33 is drawn to a kit, comprising a multivalent carrier covalently attached to one or more linear carbohydrate molecule(s).
Claim Rejections - 35 USC § 112(a); First Paragraph
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.
Claims 1-33 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 hyaluronic acid (HA) attached to SpyTag/SpyCatcher peptides at the aldehyde end of said HA, wherein said HA was attached to nanoparticle mi3 carriers, does not reasonably provide enablement for compositions comprising any multivalent carrier attached to both 1) any linear carbohydrate and 2) any antigen. 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/or use the invention commensurate in scope with these claims.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims. The claims are drawn to a vaccine composition comprising any multivalent carrier covalently attached to any one or more linear carbohydrate molecule(s) and any plurality of immunogen molecules, wherein said one or more linear carbohydrate molecules each attached to said multivalent carrier via a reducing end of said linear carbohydrate molecule(s). The claim encompasses a broad genus of nanoparticle-based vaccine constructs, including numerous possible carriers, linear carbohydrates, and immunogens. The claims are also drawn to methods of delivering said compositions to a subject in need thereof to elicit a variety of outcomes, namely in order to elicit an immune response, especially one that treats or inhibits an infection or symptoms of an infection in a subject in need thereof, wherein the composition is administered via enteral, oral, parenteral, topical, intranasal, intravaginal, intrarectal, intraocular, or intravitreal means.
The breadth of “linear carbohydrate molecule” is any organic compound (most typically monosaccharides) structured as an unbranched chain of carbon atoms rather than a ring, wherein the molecule has a carbonyl group (aldehyde (aldose, aldehyde at C1) or ketone (ketose, ketone typically at C2)) at one end and multiple hydroxyl groups. Fructose, ribose, and cellulose are all common linear carbohydrates, instant claim 2 comprises further linear carbohydrate molecules. Pathogenic organisms also comprise linear carbohydrates, such as alginate (Pseudomonas), bacterial cellulose (Salmonella), hyaluronic acid (Streptococci), curdlan (Agrobacterium), chitin (fungal cell walls), and certain homopolymeric O-antigens in the lipopolysaccharides of certain gram-negative bacteria. These molecules can be small, such as under 100 g/mol (glyceraldehyde, about 90 g/mol), up to 100,000 daltons or more (linear cellulose).
The ”reducing end” of the linear carbohydrate would be the terminal sugar unit that possesses a free hemiacetal group (or hemiketal group in ketoses) on its anomeric (C1) carbon.
The breadth of “immunogen molecules” is any substance, typically a peptide or a protein, which is capable of inducing an immune response in a subject (e.g., a mammal, such as a human). The term also refers to peptides and proteins and derivatives thereof that are immunologically active in the sense that once administered to a subject, are capable of or intended to evoke an immune response of the humoral and/or cellular type directed against that protein or peptide or a variant thereof (¶[0063]). Immunogenic molecules may be from any cancer or tumor, or be any known pathogen or immunogenic component thereof, such as any protozoa, fungi, helminths, bacteria, or virus (¶[0068]).
The breadth of any “multivalent carrier” is any carrier that presents or delivers multiple copies of the same or different antigens to a host in order to elicit an immune response (¶[0014]). Such carriers can be any of those carriers listed in instant claim 12. Such carriers typically have a repetitive array to aid in eliciting B-cell cross-linking and antibody production, and are designed to enhance the delivery of their cargo to antigen-presenting cells (APCs.)
The term “vaccine,” by definition, implies a preparation intended for active immunological prophylaxis. Prophylaxis is defined as the prevention of disease or of a process that can lead to disease.
The breadth of “prevent” was presented supra in the claim interpretation section.
State of the prior art/Predictability of the art. The fields to which the instant claims pertain, namely the vaccine art and the nanoparticle art involving covalent conjugations systems, such as SpyTag/SpyCatcher, remain highly unpredictable. The prior art demonstrates nanoparticle vaccines displaying SpyTag/SpyCatcher systems (Cohen AA, et. al. Science. 2021 Feb 12;371(6530):735-741. Epub 2021 Jan 12.) and separate systems involving carbohydrate-functionalized nanoparticles (US20210292275A1, Pub. 09/23/2021; Bartheldyová E, et. al. Bioconjug Chem. 2018 Jul 18;29(7):2343-2356. Epub 2018 Jun 25.) However, the art does not establish that combining these elements, namely simultaneous display of linear carbohydrates and multiple immunogens on a multivalent carrier, will reliably produce stable constructs, proper conjugation, or functional immune responses. The successful employment of such a system requires the correct interworking of numerous variables, such as steric effects from the immunogen and carbohydrate, conjugation efficiency to the carrier, relative loading ratios of the carbohydrate/immunogen, and preservation of the immunogenic structure and activity. Such factors are highly unpredictable without empirical validation.
For instance, the art shows that linear carbohydrates are generally poor immunogens that fail to elicit strong T-cell immunity, while their high flexibility and chemical complexity make precise surface loading on nanoparticles difficult (Toraskar S, et. al. ACS Chem Biol. 2022 May 20;17(5):1122-1130. Epub 2022 Apr 15.) A high density of linear carbohydrates on a nanoparticle surface can create a "sugar forest" that masks the antigen and inhibits its binding to target receptors. High antigen density on the surface can also restrict access to base-proximal epitopes, reducing overall antibody affinity maturation (Archambault MJ, et. al. Vaccines (Basel). 2024 Nov 19;12(11):1290.; Ols S, et. al. Immunity. 2023 Oct 10;56(10):2425-2441.e14. Epub 2023 Sep 8.) The synthesis and conjugation of linear carbohydrates is often challenging, costly, and results in heterogeneous glycol-nanoconjugates. The covalent linkage required to bind the linear carbohydrate to the carrier through reductive amination can also degrade the glycan or alter its structure. Therefore, there is considerable uncertainty in the glycoconjugate art.
Turning to the antigens, the sheer breadth of potential antigens being claimed is extraordinarily large, but, in summary, issues regarding conjugation of antigens to nanoparticles are also known, especially in the context of co-conjugation of linear carbohydrates. Linear carbohydrates and the chemical techniques used to bind them to nanocarriers can physically mask or cover critical epitopes on the antigen, hindering antibody recognition and binding. The high-density display of antigens on a nanoparticle can sometimes lead to reduced processing of that antigen by APCs compared to its native form. In certain instances, the immune system may prioritize an immune response against the carbohydrate or the nanocarrier itself, suppressing the immune response against the specific epitope of interest. Depending on how the antigen is attached to the nanocarrier, there can be an increase or decrease in the flexibility of the molecule, either of which can result in a loss of the stable and correctly folded conformation required for the desired immune response. While carbohydrate-modified nanoparticles are designed to increase APC uptake, these same receptors, namely C-type lectins, can lead to rapid clearance of the nanoparticles, providing a very narrow window for the antigen to be processed and presented to T cells.
Taken as a whole, the post-filing and prior art has shown that there is great variability in the art with regards to vaccine compositions and uses thereof, especially vaccines focused on carbohydrate conjugation to antigens and/or nanoparticles.
Working examples. No working example is disclosed in the specification that appears to have generated both a multivalent carrier system AND an immunogen; the data and examples provided focus on generating the mi3-based nanoparticles attached to HA using the SpyTag/SpyCatcher system (Figs. 1-11.) While the specification provides multiple illustrative embodiments, much of the disclosure appears to be prophetic in nature, describing how the constructs may be prepared rather than demonstrating that they have been prepared and function successfully as claimed. There is insufficient demonstration of fully assembled carriers comprising both linear carbohydrate molecules attached via the reducing end and a plurality of immunogenic molecules. From the specification, no example of any embodiment of the instant claims appears to have been reduced to practice in either generating said compositions or the use of said compositions in vivo to generate any type of immune response. No other nanocarriers aside from the mi3-based systems appear to have been generated that have the linear carbohydrates attached. No other attachment mechanism aside from the SpyTag/SpyCatcher system appears to have been employed or tested for the linear carbohydrates. No other linear carbohydrates aside from HA appear to have been attached to the mi3 nanoparticles. No examples show that the compositions could generate any immune response, which is a reasonable question as linear carbohydrates include molecules which are not typically immunogenic and, depending on the size, may mask any immune response to any attached antigens. No examples show any generation of homologous or cross-reactive immunity to any delivered immunogen, nor do any examples show therapeutic benefit from delivery of said vaccines against either homologous or heterologous antigens present in the composition. No examples demonstrate what type of immune response may be elicited upon delivery of such compositions. No examples have shown delivery of the claimed compositions through any of the routes as claimed. The methods, as claimed, do not require that the composition delivered treat the same pathogen from which the antigen/immunogen is derived, so it is unclear how such compositions could elicit such broadly therapeutic immune responses. As discussed supra, there are numerous unpredictable factors in this art, and these unpredictable factors are not sufficiently discussed or studied in the specification.
Guidance in the specification. The specification provides guidance towards the generation of mi3-based carriers for HA, wherein the HA is attached to the mi3 nanoparticles via the SpyTag/SpyCatcher system. The specification fails to provide sufficient guidance to enable the full scope of the instant claims without undue experimentation. Specifically, the disclosure fails to teach how to select compatible combinations of carriers, carbohydrates, and immunogens across the full scope of the claims, how to control the degree of substitution and/or spatial arrangement to maintain the immunogenic functionality of the system, or how to ensure that carbohydrate attachment via the reducing end is compatible with simultaneous antigen display. The figures and examples provided limited embodiments which are specific to only displaying the carbohydrate, and fail to provide generalizable teachings which would be applicable across the claimed genera.
Amount of experimentation necessary. Additional research is required in order to determine how to generate any multivalent carrier which is attached to both any linear carbohydrate via any means at its reducing end and to any immunogen. Additional research is required to determine how to use such as composition in any method of delivery to any host via any of the routes as claimed, especially in order to generate the types of therapeutic responses as claimed (e.g. homologous and/or heterologous immune responses.)
In light of the Supreme Court decision in Amgen Inc. et al. v. Sanofi et al., 143 S. Ct. 1243 (2023) (hereafter Amgen), updated guidelines were provided regarding the assessment of enablement (Federal Register, pp. 1563-1566; Pub. Jan. 10, 2024.) In Amgen, the Supreme Court unanimously affirmed that a genus of monoclonal antibodies were not enabled because when a range within a genus is claimed, there must be reasonable enablement of the scope of the range. The Court found in Amgen that due to the large number of possible candidates within the scope of the claims and the specification's corresponding lack of structural guidance, it would have required undue experimentation to synthesize and screen each candidate to determine which compounds in the claimed class exhibited the claimed functionality. In the instantly claimed invention, the breadth of the various genera in the instant claims (e.g. breadth of multivalent carrier, immunogen, linear carbohydrate, immune response type, delivery route, etc.) encompasses such a large amount of different combinations/permutations that experimentation is extraordinarily undue to enable the breadth of the claims.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to make and/or use the claimed compositions and methods.
Claims 1-20 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species 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.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
Claims 1-20 are rejected as lacking adequate descriptive support for any composition (or method of delivery of said composition), wherein the composition generated results in the claimed function of acting as a vaccine, wherein said composition allows the linear carbohydrate to be attached via its reducing end to the multivalent carrier, wherein said immunogen is also attached to said carrier.
In support of the claimed genera (e.g. carriers, linear carbohydrates, immunogens, delivery routes, immune responses), the application discloses one example in which a linear carbohydrate, hyaluronic acid (HA) is attached via its reducing end using a SpyTag/SpyCatcher system to an mi3-based nanoparticle carrier. No working examples appear to actually have reduced to practice any system which attached both the immunogen and the carbohydrate to the carrier in any fashion (see discussion supra), with all description as to how to attach both appearing to be purely prophetic in nature. Likewise, no examples showing any delivery of these compositions to any host was provided, nor was any type of immune response elicited by these claimed compositions studied. Thus, the application fails to provide examples of any species within the claimed genera.
Further, while the claims provide both a structure and a function, the application fails to draw any correlation between the two. In other words, there is no evidence that any carrier can have any linear carbohydrate attached along with any immunogen attached and still retain the ability of said carrier delivering the cargo to a host cell, or that said attached immunogens would remain immunogenic. Moreover, no correlation has been made as to which linear carbohydrates, aside from HA, and which attachment mechanisms, aside from the SpyTag/SpyCatcher system, may be used in order to achieve the claimed structure. While the specification lists various potential immunogens, including viral and bacterial antigens, the disclosure does not demonstrate that the inventors were in possession of the full scope of the claimed genus at the time of filing. A laundry list of examples does not establish possession of the claimed composition. The specification provides only limited, non-working, and largely prophetic examples, and does not disclose a representative number of species or common structural features sufficient to allow one of ordinary skill in the art to recognize members of the claimed genus. Accordingly, the specification fails to provide sufficiently concrete examples or structural features tying the listed immunogens to the claimed compositions.
With respect to the claimed methods of using said compositions, the specification fails to demonstrate that the inventors were in possession of the compositions, or the methods tied to said compositions. Given the unpredictability of immune responses and vaccine efficacy known in the art, the specification must provide more than a mere assertion that such compositions will stimulate an immune response, especially a cross-protective immune response. Given that the specification lacks in vivo or in vitro data with the claimed compositions, any details which provide correlation between the claimed structure and immunogenicity, or any representative examples demonstrating the claimed functional outcome, the disclosure again does not demonstrate that the inventors were in possession of the full scope of the claimed genus of methods at the time of filing.
Thus, in view of the above, there would have been significant uncertainty as to which combination of carriers, carbohydrates, and immunogens could be combined to generate the compositions as claimed, and how said compositions would be able confer the claimed immunogenic response in a host. In view of this uncertainty and the lack of any examples of the claimed genera, the claims are rejected for lack of adequate written description support.
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.
(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 1-32 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Petillo et. al. (US20240139312A1, Priority 05/27/2022; hereafter “Petillo”.)
The applied reference has at least one common inventor and a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
The Prior Art
Petillo teaches a vaccine composition comprising a multivalent carrier covalently attached to one or more linear carbohydrate molecules and a plurality of immunogen molecules, said one or more linear carbohydrate molecules each attached to said multivalent carrier via a reducing end of said linear carbohydrate molecules (entire document; see abstract; reference claim 1; Fig. 1; instant claim 1). Petillo teaches wherein said linear carbohydrate molecules are individually and independently selected from the group comprising chitin, partially deacylated chitin, chitosan, partially acylated chitosan, hyaluronic acid, keratin, keratin sulfate, chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, and heparin, and derivatives thereof (¶[0028][0036]; instant claim 2), specifically wherein said linear carbohydrate molecule is hyaluronic acid or a derivative thereof (¶[0036][0038-0039]; reference claim 2; instant claim 3) and wherein said linear carbohydrate molecule has a molecular weight individually and independently selected from the group consisting of about 6,000 Daltons, about 10,000, about 20,000, about 30,000, about 40,000, about 50,000 and about 110,000 Daltons (¶[0036-0038]; reference claims 1-3; instant claim 4). Petillo teaches wherein said linear carbohydrate molecules and said immunogen molecules are each covalently attached via a respective peptide tag/binding site pair to said multivalent carrier, such as the use of a SpyTag/SpyCatcher binding pair. Because claim 6 only recites an “optional” linker between the peptide tag and linear carbohydrate, the claim does not require a distinct linker structure beyond the disclosed protein residues or moieties positioned between the SpyTag/SpyCatcher attachment site and the site of the hyaluronic acid (HyA) attachment (¶[0056][0070-0075]; instant claims 5-6). Petillo teaches carbohydrate conjugation ratios within the claimed range of about 1:100 to about 100:1 (¶[0200]; instant claim 7). Petillo teaches both homologous and heterologous immunogen embodiments, in that the homotypic OspC-mi3 nanoparticles are displaying homologous immunogens while the mosaic-8-OspC-mi3 nanoparticles disclose a plurality of heterologous immunogens, including 8 different OspC SpyTag variants (Example 32; ¶[0018][0066][0087][0208-0209][0255][0258]; Fig. 6; instant claims 8-9, 19). Petillo discloses immunogens derived from protozoa, fungi, helminths, bacteria, and viruses (¶[0043-0050]; instant claim 10), and notes that the pathogens may include influenza viruses, rhinoviruses, human immunodeficiency viruses (HIV), respiratory syncytial virus (RSV), coronaviruses, dengue viruses, hepatitis viruses, West Nile virus, Middle East respiratory syndrome–related coronavirus (MERS-CoV), norovirus, Marburg viruses, Zika virus, orthopoxviruses, Togaviridae, Ebola virus, Borrelia, Babesia, methicillin-resistant Staphylococcus aureus (MRSA), Legionella, Chlamydia, Plasmodia, Streptococcus pneumoniae, Vibrio cholerae, Listeria, Clostridia, Salmonella, Bordetella, Enterococci, Treponemia, Amoeba, Neisseria, and Giardia (abstract; ¶[0043-0052]’ instant claim 11). Petillo discloses carriers including nanoparticles, nanotubes, nanowires, dendrimers, liposomes, ethosomes and aquasomes, polymersomes and niosomes, foams, hydrogels, cubosomes, quantum dots, exosomes, and macrophages (¶[0057]; instant claim 12). Petillo teaches the nanoparticle may comprise a virus-like particle (VLP), such as mutated AP205 VLPs(¶0060-0061]; instant claims 13-14). Petillo teaches the nanoparticle may be a self-assembling nanoparticle comprised of a plurality of particle-forming proteins, wherein said self-assembling nanoparticle comprises a plurality of particle-forming proteins of 2-dehydro-3-deoxy-phosphogluconate (KDPG) aldolase or a variant thereof, or wherein said self-assembling nanoparticle is selected from the group comprising an i301 nanoparticle or a variant thereof, and a mi3 nanoparticle or a variant thereof. (reference claims 9, 12-14; instant claims 15-17). Petillo teaches wherein said plurality of immunogen molecules and said one or more linear carbohydrate molecules are each covalently attached to said particle-forming proteins of said self-assembling nanoparticle (reference claim 15; instant claim 18). Petillo teaches a method of stimulating an immune response in a subject in need thereof, or for treating or preventing an infection in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of the vaccine composition comprising the multivalent carrier, wherein said vaccine composition administration is independently and individually selected from the group comprising enteral, oral, parenteral, topical, intranasal, intravaginal, intrarectal, intraocular, and intravitreal, thereby stimulating an immune response in the subject, or improving the survival rate, or preventing the disease or disorder caused by the infection (reference claims 17-20; instant claims 20-24). Petillo teaches that the methods induce neutralizing and cross-reactive neutralizing responses against additional immunogens different from said immunogens in said plurality of immunogens (reference claim 21; instant claim 25), and the vaccine composition may be administered one or more times (reference claim 22; instant claim 26) and may be a first vaccine at the first administration and a second vaccine at the second administration, wherein said vaccines may be the same or different (reference claims 23-25; instant claims 27-29.) Petillo teaches that said administration of said first vaccine composition and said second vaccine composition are independently and individually selected from the group comprising enteral, oral, parenteral, topical, intranasal, intravaginal, intrarectal, intraocular, and intravitreal (reference claim 26; instant claim 30), wherein administering to said subject said second vaccine composition occurs about two, three, four, five, six, seven, eight weeks, 10 weeks, 12 weeks, 16 weeks, 20 weeks, 24 weeks, 28 weeks, 6 months, 1 year, 5 years, or 10 years, after administering to said subject said first vaccine composition (reference claim 27; instant claim 31). Petillo teaches a kit comprising a multivalent carrier covalently attached to one or more linear carbohydrate molecules and a plurality of immunogen molecules (reference claim 28, ¶[0164]; instant claim 32).
Petillo therefore teaches every limitation of instant claims 1-32, and anticipates the invention encompassed by said claims.
Claim 33 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bartheldyová et. al. (Bartheldyová E, et. al. Bioconjug Chem. 2018 Jul 18;29(7):2343-2356. Epub 2018 Jun 25.; hereafter “Bartheldyova”).
The Prior Art
Bartheldyova teaches hyaluronic acid (HA) as a linear carbohydrate polymer that is conjugated via its reducing end to nanoparticle or liposomal delivery systems (entire document; see e.g. abstract, Figs. 1-2, 9, p. 2346, ¶ bridging cols.) A “multivalent carrier” is defined as per instant claim 12 as being a liposome. Claim 33 is directed towards a kit comprising a multivalent carrier covalently attached to one or more linear carbohydrate molecules. Bartheldyova teaches a composition comprising liposomes with HA attached via its reducing end to said liposome. Such a composition is understood to be a “kit” as claimed in instant Claim 33, as only the liposome and carbohydrate components of the kit are specified and according to the specification, “kit” is not explicitly defined. According to the specification, a kit may simply comprise a multivalent carrier complex (¶[0195]). Bartheldyova therefore teaches the limitations of instant claim 33.
For at least these reasons, Bartheldyova teaches the limitations of instant claim 33, and anticipates the invention encompassed by said claim.
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 1-13, 15, and 18-32 are rejected under 35 U.S.C. 103 as being unpatentable over Bartheldyova as applied to claim 33 above, and further in view of
Bazzill et. al. (US20180021453A1, Pub. 01/25/2018; hereafter “Bazzill”); and
Graham et. al. (WO2021163365A1, Pub. 08/19/2021; hereafter “Graham”.)
The Prior Art
The teachings of Bartheldyova have been set forth supra. To further, Bartheldyova teaches hyaluronic acid (HA) as a linear carbohydrate polymer that is conjugated via its reducing end to nanoparticle or liposomal delivery systems (entire document; see e.g. abstract, Figs. 1-2, 9, p. 2346, ¶ bridging cols; instant claims 2-3, 12.) Bartheldyova teaches the use of such HA-conjugated liposomes in the vaccine field (abstract; p. 2348, rt. Col., ¶2; p. 2350, rt. Col., ¶1) and that liposomes have been used in vaccines with bioactive agents mounted on the surface (p. 2344, left col., ¶1). Bartheldyova teaches low molecular weight (MW) HA is below 100 kDa, and has proinflammatory and proliferative effects (p. 2349, rt. Col., ¶4; instant claim 4), but that the low MW HA can form micelles and inhibit the ability of the resulting liposomes to encapsulate their payload (p. 2349, left col., ¶2).
While Bartheldyova teaches multivalent carriers with HA attached via its reducing end to said carrier, and teaches that said carriers may be used in vaccines or to deliver payloads to a host, Bartheldyova fails to explicitly teach immunogens in the composition along with said HA-conjugated carriers. However, such compositions would be obvious modifications for a skilled artisan, given the teachings of Bazzill and Graham.
Bazzill teaches multivalent carrier systems, such as nanoparticles and virus-like particles (VLPs), (¶[0026-0027][0063][0103]; Figs. 16-17) which are complexed with HA to use as a vaccine delivery platform (¶[0062-0063]; instant claims 12-13). Bazzill teaches said hybrid NPs which comprise the HA and antigen can be engineered to be multivalent and present multiple cargo on the surface of the particle (¶[0181-0182]). The immunogens presented may be from bacterial, viral, or fungal pathogens (¶[0112]; instant claim 10), and can include such pathogens as Streptococcus pneumoniae, influenza A & B viruses, RSV, HIV, and Vibrio cholerae (¶[0112]; instant claim 11). Bazzill teaches the covalent attachment of the HA and antigens to said NP (Fig. 8; reference claim 12). Bazzill teaches pharmaceutical compositions comprising said NPs (¶[0007]) and the use of said NP in methods of delivering said compositions to a subject to elicit an immune response against a pathogen which induces protective immunity (reference claims 21-23; ¶[0101][0139]), wherein the NPs are delivered mucosally (e.g. intranasally, intrapulmonary, vaginally, rectally), dermally, or transdermally (¶[0036-0037][0134-0137][0141-0142]; instant claims 20-24, 30). Bazzill teaches prime/boost vaccination regimens wherein the boosting dose was delivered on day 28 (¶[0165]; instant claims 26, 31) wherein the compositions delivered in the prime/boost were identical (¶[0165]; instant claims 27-28) or different (¶[0175]; instant claim 29). Bazzill teaches kits which comprise the NP compositions (¶[0054]; instant claim 32).
Graham teaches nanoparticle vaccine platforms for the delivery of SARS CoV-2 antigens (entire document; see abstract; p. 2, ¶3; instant claims 10-11). Said nanoparticle platforms may be self-assembling protein nanoparticles (SAPNs)(p. 2, ¶3, pp. 14-15, ¶ bridging pages; instant claim 15) or VLPs (pp. 19-20, ¶ bridging pages; instant claims 12-13). Graham teaches that the composition may be polyvalent or monovalent (pp. 40-41, ¶ bridging pages; instant claims 8-9). Graham teaches a bifunctional molecule can be used to link two molecules into one continuous molecule (p. 12, “Linker and linked”) such as the SpyTag:SpyCatcher system (Example 3 at p. 47; Figs. 4-6; instant claims 5-6, 18-19). Graham teaches analysis of the molar ratio of each component in the nanoparticle system to determine the conjugation efficiency (p. 50, ¶2; instant claim 7). Graham teaches that the SpyLinked nanoparticles comprising SARS CoV-2 antigens elicited neutralizing antibodies in vivo (p. 50, ¶3; Example 2 starting at p. 46) and can be used in methods of eliciting therapeutic or protective immune responses in a host (p. 2, ¶4, p. 9, ¶2-3, p. 12, ¶2; instant claims 20-24). Graham teaches that the platform could elicit protection against heterologous or homologous subtypes of viruses (p. 44, ¶2; instant claim 25) and that the compositions can be administered in prime-boost vaccination regimens, wherein the priming and boosting compositions are the same or different and administered over days, weeks, or months (p. 14, ¶3; p. 41, ¶2; instant claims 26-29, 31). Graham teaches the composition may be administered via intramuscular, intradermal, subcutaneous, intravenous, intra-arterial, intra-articular, intraperitoneal, intranasal, sublingual, tonsillar, oropharyngeal, or other parenteral and mucosal routes (p. 37, ¶2; instant claim 30).
It would have been obvious to a person of ordinary skill at the time of the invention to combine the teachings of Bartheldyova, Bazzill, and Graham to arrive at the instant invention of instant claim 1, given that each reference addresses improving vaccine composition design through multivalent presentation and covalent conjugation strategies. Nanoparticle-based vaccine platforms are known to enhance immune responses by presenting multiple copies of antigens in a repetitive manner. Further, the use of established conjugation chemistries (e.g. carbohydrate conjugation via the reducing end of the carbohydrate, protein ligation systems such as SpyTag/SpyCatcher) represents the application of known, modular techniques for assembling complex vaccine constructs to yield predictable results.
It would have been obvious to one of ordinary skill in the art to modify the methods and compositions taught by Bartheldyova in order to improve upon the vaccine systems suggested by Bartheldyova, thereby generating HA-conjugated multivalent carriers which also comprised pathogenic antigens. One would have been motivated to do so, given the suggestion by Graham and Bazzill that multivalent carriers were known in the art and could display different antigens on the surface of the carriers through different types of systems. There would have been a reasonable expectation of success, given the knowledge that conjugations systems for carbohydrates and proteins were known in the art, as taught by Bartheldyova, Bazzill, and Graham, and also given the knowledge that such multivalent carriers were desirable to display and deliver multiple homologous or heterologous antigens simultaneously. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claims 14 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Bartheldyova, Bazzill, and Graham as applied to claim 1-13, 15, and 18-33 above, and further in view of Cohen et. al. (Cohen AA, et. al. PLoS One. 2021 Mar 4;16(3):e0247963.; hereafter “Cohen”.)
The Prior Art
The teachings of Bartheldyova, Bazzill, and Graham have been set forth supra. While all three teach nanoparticles which comprise particles conjugated to the surface of said nanoparticle, and Graham teaches SAPNs, and Bazzill and Graham teach VLPs, none of these references alone or in combination appear to specifically teach examples of VLPs, such as Ap205 VLPs, and none of these references alone or in combination appear to specifically teach examples of SAPNs, such as mi3 or i301 nanoparticles. However, such nanoparticles were known in the art at the time of filing, as evidenced by Cohen.
Cohen teaches SpyCatcher-based nanoparticle platforms for presentation of a diverse array of different influenza virus HA trimers (entire document; see abstract.) Said nanoparticles used by Cohen were either AP205 VLPs or mi3 SAPNs (entire document; see abstract.)
It would have been obvious to use AP205 VLPs or mi3 SAPNs for multivalent carriers, as such carriers were well-known in the art at the time of filing as highly immunogenic nanoparticle scaffolds capable of displaying multiple epitopes for vaccine applications. Said carriers were compatible with SpyTag/SpyCatcher covalent attachment systems, as evidenced by the teachings of Cohen. Given the combined teachings of Bartheldyova, Bazzill, Graham, and Cohen, it would have been obvious to arrive at the limitations of instant claims 14 and 16-17 with a reasonable expectation of success.
It would have been obvious to one of ordinary skill in the art to modify the methods and compositions taught by Bartheldyova, Bazzill, and Graham in order to use specific examples of VLPs or SAPNs for the multivalent carrier systems. One would have been motivated to do so, given the suggestion by Cohen that multivalent carriers, such as AP205 and mi3, were known in the art and could display different antigens on the surface of the carriers through different types of systems. There would have been a reasonable expectation of success, given the knowledge that conjugations systems for carbohydrates and proteins were known in the art, as taught by Bartheldyova, Bazzill, Cohen, and Graham, and also given the knowledge that such multivalent carriers were desirable to display and deliver multiple homologous or heterologous antigens simultaneously. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of copending Application No. 19/256,289 in view of Bartheldyová et. al. (Bartheldyová E, et. al. Bioconjug Chem. 2018 Jul 18;29(7):2343-2356. Epub 2018 Jun 25.; hereafter “Bartheldyová”.)
Both sets of claims are drawn to vaccine compositions comprising a plurality of antigens attached to a carrier, wherein the antigens are from Babesia, Borrelia, or Chlamydia bacteria. Both claim that the carrier is a multivalent carrier. Both claim that the carrier may present two or more immunogens, and that the carrier may be a nanoparticle such as a VLP, a self-assembling nanoparticle, peptide or protein-based nanoparticles, lipid nanoparticles, or combinations thereof. Both claim the self-assembling nanoparticle may be a KDPG aldolase-based particle, such as an i301 or a mi3 nanoparticle. Both claim the immunogens are covalently attached to the carrier using SpyTag/SpyCatcher technology. Both claim the composition may be used for enteral, oral, parenteral, topical, intranasal, intravaginal, intrarectal, intraocular, and intravitreal delivery to stimulate an immune response in a subject. Both claim the vaccine may be used to elicit neutralizing or cross-neutralizing antibody responses against homologous or heterologous pathogens, and can be administered one or more times. Both claim that the composition may be part of a heterologous prime/boost vaccine regimen. Both claim the administration of the second composition may be about 2-28 weeks after the first administration, and both claim kits comprising said vaccines. The main difference is that while the ‘289 claims provide that an adjuvant may be in the composition, the ‘289 claims do not require the presence of a linear carbohydrate to be attached to the carrier in addition to the antigen. However, such a difference would be an obvious modification of the ‘289 claims, given the suggestion by Bartheldyová. Bartheldyová teaches generation of nanoparticles which comprise the linear carbohydrate hyaluronic acid (HA) specifically attached to said nanoparticle (in this instance, a liposome) via a specific reduction coupling at the HA terminus to generate the HA-coupled liposomes (entire document; see Fig. 2.) Bartheldyová teaches low-molecular-weight HA triggers pro inflammatory responses while high-molecular-weight HA triggers anti-inflammatory responses. The unique properties of HA enhanced some attempts to apply it in clinical practice, especially in drug targeting to CD44 expressing cancer cells, treatment of chronic wound and inflammation, as well as targeting of dendritic cells to enhance the efficacy of vaccines (p. 2349, rt. Col., ¶2). Bartheldyová teaches the HA-liposomes may be further engineered to carry antigens and molecular adjuvants for vaccination purposes (Fig. 8; p. 2350, rt. Col., ¶1). Therefore, it would be obvious to try and attach antigens and HA to nanoparticles, such as liposomes, for vaccination purposes, given the teachings of Bartheldyová, making the differences between the instant claims and the ‘289 claims patentably indistinct.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. US20170224612A1. Teaches mucoadhesive carriers that use hyaluronic acid. Not utilized as rejection would be redundant to those set forth supra.
US20160243246A1. Teaches the use of hyaluronic acid-nucleic acid conjugates for the development of in vivo nucleic acid delivery systems. Not utilized as rejection would be redundant to those set forth supra.
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/RACHEL B GILL/
Primary Examiner, Art Unit 1671
Prosecution Insights