DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election without traverse of Group I (claims 1-10 and 19-21) in the reply filed on 06/05/2026 is acknowledged. Claims 1-15 and 17-21 are pending; claims 11-15, 17 and 18 are withdrawn from prosecution as being drawn to non-elected subject matter. Claims 1-10 and 19-21 are examined.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/21/2025 was considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-10 and 19-21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The claims are described as to what the components are supposed to be able to perform instead of actual structure.
As such, the metes and bounds of the claims could not be determined.
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 1-10 and 19-21 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.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). (emphasis added). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
“[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For antibodies, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor, 97 USPQ2d at 1875.
Lastly, even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), it is noted that to show invention, a patentee must convey in its disclosure that is “had possession of the claimed subject matter as of the filing date. Demonstrating possession “requires a precise definition” of the invention. To provide this precise definition” for a claim to a genus, a patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen at page 1358).
Also, it is not enough for the specification to show how to make and use the invention, i.e., to enable it (see Amgen at page 1361).
An adequate written description must contain enough information about the actual makeup of the claimed products – “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361).
In the instant case, the specification discloses preparation of a vaccine comprising a specifically prepared Bovine Serum Albumin (BSA) or Covid Spike protein. However, the claims broadly encompass any antigenic protein (since the composition, being envision as a vaccine, needs to elicit an immunological response when used in vivo). Thus, the claims are directed to a genus of immunologically capable antigens which have the property of inducing cavitation on exposure to ultrasound, wherein the instant specification does not describe representative examples to support the full scope of the claims because the instant specification discloses only a few exemplary vaccine compositions.
The genus of immunologically active proteins is extremely vast, comprising a wide variety of antigens with different structures and properties. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The “structural features common to the members of the genus” needed for one of skill in the art to 'visualize or recognize' the members of the genus takes into account the state of the art at the time of the invention.
Claims 1-10 and 19-21 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 compositions comprising BSA or Covid Spike protein, wherein the particle size is in the range of from 100nm to 10000nm, the cross section of at least one surface indentation forms a conic section, wherein at least one surface indentation has a depth of at least 10nm and the particle comprises one or two indentations having an opening size which is 20% or more of the size of the particle and capable of generating inertial cavitation when the composition is exposed to ultrasound at 1.8MPa and 265kHz, does not reasonably provide enablement for the full breadth of the independent claim 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The claims are drawn to a transdermal vaccine composition comprising a plurality of polypeptide particles (having at least one surface indentation) suitable for inducing cavitation on exposure to ultrasound and at least one pharmaceutically acceptable carrier or diluent. Further limitations are to the particle size (in the range of from 100nm to 10000nm). The cross section of at least one surface indentation forms a conic section that has depth of at least 10nm and/or the particle comprises one or two indentations having an opening size which is 20% or more of the size of the particle. The polypeptide particles are capable of generating inertial cavitation when the
composition is exposed to ultrasound at 1.8MPa and 265kHz.
It is clear from the Specification that the vaccine composition has to have a very specific composition that would be able to fulfill all the requirements and has to be made considering all the desired properties.
The specification describes a polypeptide shell refers to a shell which is formed from polypeptide and comprises cross-linked polypeptide particles ([0114]). Spherical particles having a water-immiscible core and a polypeptide shell, are produced by such homogenization methods, are known in the art, and Suslick et al., J. Amer. Chem. Soc., 112, 7807-7809,1990; Desai et al., U.S. Pat. No. 5,439,686 -both cited by Applicant) ([0171]). Following the creation of the polypeptide shell, the particles of the invention undergo a step in which the volatile component(s) are removed, causing deformation of the particle and thus the desired indented structure. The nature and amount of volatile component which is present in the water-immiscible phase affects the particle size and may be used as a factor in controlling the size of particle produced. Variation in the size of the indentation may also be relevant to the cavitation effects generated by the indented particle, due to the change in the potential for gas bubbles to be trapped within the cavity of the indentation. A volatile content of at least 40% by volume, preferably from 45 to 55% by volume in the water-immiscible phase, preferably around 50% by volume (or 1:1), has been found to provide improved cavitation properties ([0172]-[0174]).
It is clear for the above teachings that the transdermal vaccine composition broadly claimed in the independent claim 1 is actually an extremely specific composition that is obtained only by following a strict protocol.
The specification provides working examples in which vaccine compositions comprising the Covid spike protein (the immunogenic agent) and an adjuvant are transdermally administered. However, the Applicant broadly claims a transdermal vaccine composition that comprise a plurality of polypeptide particles (having at least one surface indentation) suitable for inducing cavitation on exposure to ultrasound and at least one pharmaceutically acceptable carrier or diluent.
Such broad claims would necessitate a person of ordinary skill in the art to try to obtain a working transdermally delivered vaccine by performing a huge amount of experimentation with unpredictable results. This amount of experimentation is considered undue and only following the strict methods by using the Covid Spike protein, and the detailed teachings of indicated in claims 8-10 and 19-20 a person of ordinary skill in the art would be able to obtained the desired Transdermal vaccine composition.
The prior art made of record and not relied upon is considered pertinent to
applicant's disclosure and it could be used, depending on how Applicant amends the claims in response to the Non-final rejection:
Huang et al., Impact of antigen-adjuvant associations on antigen uptake and
antigen-specific humoral immunity in mice following intramuscular injection,
Biomed. Pharmacother., 118, 2019, DOI:10.1016/J.BIOPHA.2019.109373 (cited
by Applicant). The reference discloses the concept of an immunogenic
composition comprising a squalene-based double oil emulsion (PELC) and a
plurality of pathogenic protein antigens that allow efficient antigen uptake and
antigen-specific humoral immunity, when injected intramuscularly into mice,
wherein the PELC particles allows for a W/O/W multiple phase dispersion
comprising an oily barrier that separates internal and external aqueous phases
wherein antigens can be either encapsulated and/or attached to the outer phase
and wherein the said particles are about 300-500 nm in diameter (figure 1;
materials and methods page 2). The mouse studies disclosed demonstrate how to arrive at optimal vaccine formulations that deepen our understanding on how
antigen-adjuvant associations can govern the cellular uptake and transportation of protein antigen into the draining lymph nodes and prolong antigen-specific humoral immunity (p. 4-6).
Huang et al., Emulsified Nanoparticles Containing Inactivated Influenza Virus and CpG Oligodeoxynucleotides Critically Influences the Host Immune Responses in Mice, Plos One, 5, e12279, 2010. The reference discloses a PELC (a proprietary water-in-oil-in-water nanoemulsion comprising of bioresorbable polymer/ SpanH85 /squalene) adsorbed inactivated H5H1 virus and its use as a vaccine to induce potent antigen-specific cross-clade neutralizing antibodies. PELC can be used for effective single-dose immunization and thus play an important role in antigen sparing influenza pandemic preparedness.
Zhou et al., Nano-formulations for transdermal drug delivery: A review, Chinese chemical letters, 29, 1713-1724, 2018 (cited by Applicant) reviews the state of the art regarding the use of nano-formulations such as oil-in water- based nanoemulsions for transdermal hydrophilic drug delivery wherein the delivery method uses ultrasound to facilitate the permeability of the therapeutical compound in question through the skin. The documents explain the advantages of such a delivery system over oral administration and intramuscular injection as easy to use, non-invasive and improved patient compliance. It also reduces the fluctuation of the drug concentration in the blood, provides steady plasma levels and fewer chances of overdose and easy detection of the drug in question. At the same time, it evades the gastrointestinal environment, such as pH, enzymatic activity, and the interference of drug and food interaction on the drug efficacy and the 'first pass effect' (where active drug molecules can be converted to inactive molecules or even to molecules responsible for side effects) by the liver. These conditions lengthen the therapeutic effect of drug in question with shorter half-life and enhance their long-term stability of drug.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLY GERALD STOICA whose telephone number is (571)272-9941. The examiner can normally be reached M-F 8-5 EST.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/Primary Examiner, Art Unit 1647
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