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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/27/2026 has been entered.
Withdrawal of Rejections
The response and amendments filed on 02/27/2026 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated here for brevity, have been withdrawn necessitated by Applicant’s formality correction and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining, if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s Response to Arguments section.
Briefly, the previous claim rejections under 35 U.S.C. 102 for anticipation have been withdrawn necessitated by Applicant’s arguments; however, new grounds of rejection are set forth below. The previous claim rejections under 35 U.S.C. 103 for obviousness have been withdrawn necessitated by Applicant’s arguments; however, new grounds of rejection are set forth below.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Objections
Claim 24 is objected to because of the following informalities: “the a surface” should read “a surface”. Appropriate correction is required. This is an objection, not a rejection, because this appears to be a typographical error.
Claim Rejections - 35 USC § 112(a), Written Description
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.
Claims 1-6, 9, 11, 13, 15-16, 18-21, 23-26, and 28 are rejected under 35 U.S.C. 112(a) 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.
Independent claim 1 recites “A hydrogel composition comprising cross-linked bacteriophages.” Applicant is broadly claiming the entire bacteriophage genus.
With regards to the written description pertaining to the bacteriophages, the instant specification states “In accordance with an aspect, there is provided a hydrogel composition comprising cross- linked bacteriophages. In an aspect, the bacteriophages self-assemble into bundles. In an aspect, the bacteriophages comprise filamentous bacteriophages. In an aspect, the bacteriophages comprise Escherichia coli bacteriophages. In an aspect, the bacteriophages comprise f1, M13, or fd bacteriophages, or combinations thereof” (see, e.g., instant specification, pg. 2, lines 1-9). Moreover the instant specification states “In an aspect, the at least two different bacteriophage strains target the same bacterial species or different bacterial species to treat complex infections” (see, e.g., instant specification, pg. 3, lines 2-3). Additionally, the instant specification states “The bacteriophages may be of any type and may infect any bacteria, but in typical aspects, the of bacteriophages comprise filamentous bacteriophages. In some aspects, the bacteriophages comprise Escherichia coli bacteriophages including, but not limited to, f1, M13, or fd bacteriophages, or combinations thereof. Typically, the bacteriophages are M13 bacteriophages” (see, e.g., instant specification, pg. 10, lines 4-8). Therefore, the instant specification states that the bacteriophages are specifically f1, M13, or fd bacteriophages, but then goes on to state that the bacteriophage strains can be any strain. Furthermore, the instant specification reduces to practice compositions solely comprising M13 phages (see, e.g., instant specification, Examples 1-7). Moreover, the instant specification does not set forth a representative number of species for the claimed genus, wherein the genus is bacteriophages. Applicant discloses three bacteriophages (i.e., f1, M13, and fd bacteriophages), which is not sufficient for the claimed genus (see, e.g., MPEP 2163(II)(3)(ii)) because there can be other bacteriophages, especially unknown/undiscovered bacteriophages, that can be crosslinked to produce a hydrogel.
The prior art teaches that there are an estimated 1031 phage particles on the planet and have been isolated from every environment in which bacteria exist (see, e.g., Keen, “A century of phage research: Bacteriophages and the shaping of modern biology”, pg. 2). Furthermore, the prior art teaches production of hydrogels comprising genetically engineered M13 phages (see, e.g., Sawada, abstract). Kashiwagi (Filamentous Phage-Based Extra Cellular Matrix; 2008 – cited in the IDS filed on 01/11/2022) teaches the production of M13 phage crosslinked hydrogels, wherein the bacteriophages are crosslinked with glutaraldehyde (see, e.g., Kashiwagi, Section 2.5, pg. 393). Chen (Assembly of Viral Hydrogels for Three-Dimensional Conducting Nanocomposites; 2014 – cited in the IDS filed on 01/11/2022) teaches utilization of M13 bacteriophages that are genetically programmed to bind single-walled carbon nanotubes to form crosslinked hydrogel scaffolds (see, e.g., Chen, Introduction, pg. 5101). Therefore, the prior art primarily focuses on generation of hydrogels using M13 bacteriophages; however, since so many bacteriophages exist, there is unpredictability as to if there are other bacteriophages that can be crosslinked to produce hydrogel compositions, which reads upon the instantly claimed invention (see, e.g., MPEP 2163(II)(3)(ii) - "[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.")
The state of the art and the instant specification generally supports Applicant’s possession of f1, M13, and fd bacteriophages; however, the prior art does not provide support for the possession of the entire claimed bacteriophage genus, which would also include bacteriophages unknown/undiscovered at the time of filing which can crosslink to form a hydrogel.
Claim Rejections - 35 USC § 112(a), Scope of Enablement
Claims 1-6, 9, 11, 13, 15-16, 18-21, 23-26, and 28 rejected under 35 U.S.C. 112(a) because the specification, while being enabling for a hydrogel composition comprising cross-linked f1, M13, and fd bacteriophages, does not reasonably provide enablement for all bacteriophages. 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 the invention commensurate in scope with these claims.
In re Wands (858 F2d, 721, 727, 8 USPQ 2d 1400, 1404 (Fed Cir. 1988)), the issue of
enablement in molecular biology was considered. It was held that the following factors should be
considered to determine whether the claimed invention would require the skilled artisan undue
experimentation:
1) Amount of experimentation necessary;
2) Amount of direction or guidance presented;
3) Presence or absence of working examples;
4) Nature of the invention;
5) State of the prior art;
6) Relative skill of those in the art;
7) Predictability or unpredictability of the art; and
8) Breadth of the claims.
Nature of the invention: The invention is directed towards a composition comprising cross-linked bacteriophages.
Breadth of the claims: As claimed, the composition comprises all bacteriophages.
Amount of direction or guidance presented: The instant specification states “In accordance with an aspect, there is provided a hydrogel composition comprising cross-linked bacteriophages. In an aspect, the bacteriophages self-assemble into bundles. In an aspect, the bacteriophages comprise filamentous bacteriophages. In an aspect, the bacteriophages comprise Escherichia coli bacteriophages. In an aspect, the bacteriophages comprise f1, M13, or fd bacteriophages, or combinations thereof” (see, e.g., instant specification, pg. 2, lines 1-9). Moreover the instant specification states “In an aspect, the at least two different bacteriophage strains target the same bacterial species or different bacterial species to treat complex infections” (see, e.g., instant specification, pg. 3, lines 2-3). Additionally, the instant specification states “The bacteriophages may be of any type and may infect any bacteria, but in typical aspects, the of bacteriophages comprise filamentous bacteriophages. In some aspects, the bacteriophages comprise Escherichia coli bacteriophages including, but not limited to, f1, M13, or fd bacteriophages, or combinations thereof. Typically, the bacteriophages are M13 bacteriophages” (see, e.g., instant specification, pg. 10, lines 4-8). Therefore, the instant specification states that the bacteriophages are specifically f1, M13, or fd bacteriophages, but then goes on to state that the bacteriophage strains can theoretically be any strain.
Presence or absence of working examples: The instant specification teaches preparation of hydrogels with M13 bacteriophages (see, e.g., instant specification, Examples 1-7). Based on the Applicant’s disclosure, the Applicant would not be enabled for all bacteriophages. There is no guidance on the preparation of hydrogels with bacteriophages besides M13 bacteriophages, as Applicant only reduced to practice hydrogel compositions comprising cross-linked M13 bacteriophages.
State of the prior art: The prior art of Sawada (Controlled release of antibody proteins from liquid crystalline hydrogels composed of genetically engineered filamentous viruses; 2017 – cited in the IDS filed on 01/11/2022) teaches the production of hydrogels comprising genetically engineered M13 phages (see, e.g., Sawada, abstract). Moreover, Sawada teaches that “M13 have been used as a component for the construction of soft materials in various fields, such as sensors, electronics, and devices,18–23 because of their defined size and dimensions (4.5 nm width and 900 nm length, molecular weight of 16.3 MDa), ease of surface modification through genetic24 or chemical25 methods, and capability for self-assembly into regularly ordered liquid crystalline structures” (see, e.g., Sawada, Introduction, pgs. 146-147). Kashiwagi (Filamentous Phage-Based Extra Cellular Matrix; 2008 – cited in the IDS filed on 01/11/2022) teaches the production of M13 phage crosslinked hydrogels, wherein the bacteriophages are crosslinked with glutaraldehyde (see, e.g., Kashiwagi, Section 2.5, pg. 393). Chen (Assembly of Viral Hydrogels for Three-Dimensional Conducting Nanocomposites; 2014 – cited in the IDS filed on 01/11/2022) teaches utilization of M13 bacteriophages that are genetically programmed to bind single-walled carbon nanotubes to form crosslinked hydrogel scaffolds (see, e.g., Chen, Introduction, pg. 5101). Therefore, the prior art primarily focuses on generation of hydrogels using M13 bacteriophages. Furthermore, the prior art teaches that there are an estimated 1031 phage particles on the planet and have been isolated from every environment in which bacteria exist (see, e.g., Keen, “A century of phage research: Bacteriophages and the shaping of modern biology”, pg. 2).
Relative skill of those in the art: Based on the state of the prior art, the relative skill of those in the prior art pertaining to developing hydrogel compositions with cross-linked bacteriophages is low due to the fact that there are so many bacteriophages that exist on the planet, and due to the fact that development of cross-linked hydrogel compositions is primarily performed with M13 bacteriophages.
Predictability or unpredictability of the art: The level of unpredictability within the art is high, as there are many types of bacteriophages, all with different structures and functions; therefore, it is unpredictable as to whether these bacteriophages can be cross-linked and formed into a hydrogel composition because the prior art primarily focuses on crosslinking M13 bacteriophages to form hydrogels. Further, the specification does not contemplate how other bacteriophages, besides f1, M13, or fd bacteriophages, can be incorporated into hydrogel compositions. Therefore, the level of unpredictability within the art is high.
Amount of experimentation necessary: Since there are many types of bacteriophages that exist on the planet, one of ordinary skill in the art would have undue experimentation in order to determine if hydrogel compositions can be produced with other bacteriophages with different structures and functions, besides M13 bacteriophages. Also, experimentation is necessary to determine how these other bacteriophages can cross-link. Therefore, the amount of experimentation is high as there is undue experimentation to determine if and how other bacteriophages can crosslink to produce hydrogel compositions.
Claim Rejections - 35 USC § 102, Anticipation
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-6, 9, 11, 16, and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sawada (Regular assembly of filamentous viruses and gold nanoparticles by specific interactions and subsequent chemical crosslinking; 2014 – cited in the IDS filed on 01/11/2022 – newly cited).
Sawada’s general disclosure relates to “regular assemblies composed of M13 phages displaying gold-binding A3 peptides14 at the phage termini (A3 phages) and the GNPs (Figure 1) based on specific interactions between A3 peptides at the phage termini and the GNP surfaces, as well as the subsequent chemical crosslinking of the phages. The GNPs formed well-organized structures in mixed solutions of A3 phages and GNPs. When crosslinking was performed between the A3-phage molecules, the mixed solutions were transformed into hydrogels” (see, e.g., Sawada, Introduction, pg. 511).
Regarding claim 1 pertaining to the hydrogel composition comprising cross-linked bacteriophages, Sawada teaches M13 phages displaying gold-binding A3 peptides at the phage termini interacting with gold nanoparticles (GNPs) to result in chemical crosslinking of the phages (see, e.g., Sawada, Introduction, pg. 511). Furthermore, when crosslinking was performed between the A3-phage molecules, the mixed solutions were transformed into hydrogels (see, e.g., Sawada, Introduction, pg. 511).
Regarding claims 2-6 pertaining to the bacteriophages, Sawada teaches M13 bacteriophages, which are filamentous, Escherichia coli bacteriophages (see, e.g., Sawada, Introduction, pg. 511 & “Experimental Procedures”, pg. 511). Furthermore, M13 bacteriophages inherently self-assemble into bundles (see, e.g., Sawada, “Controlled release of antibody proteins from liquid crystalline hydrogels composed of genetically engineered filamentous viruses; 2016 – Art of Record).
Regarding claim 9 pertaining to crosslinkers, Sawada teaches gold nanoparticles as crosslinkers (see, e.g., Sawada, Introduction, pg. 511).
Regarding claim 11 pertaining to the hydrogel exhibiting properties, Sawada teaches that the crosslinked bacteriophage has uniformed birefringence (see, e.g., Sawada, “Results and Discussion”, pg. 514 & Figure 4C). Furthermore, Sawada teaches the instantly claimed composition, which would inherently exhibit one or more of the claimed properties, such as bioactivity, degradability, self-healing, fluorescence, and/or birefringence (see, e.g., MPEP 2114(I)).
Regarding claim 16 pertaining to genetically engineered bacteriophages, Sawada teaches “A3 peptides (sequence: AYSSGAPPMPPF) with gold-binding capabilities14 were genetically fused to pIII minor coat proteins of M13 phages via Gly-Gly-Gly-Ser spacers using the Ph.D. Peptide Display Cloning System (New England Biolabs, Ipswich, MA, USA)” (see, e.g., Sawada, “Experimental Procedures”, pg. 511) and that “A3 peptides were displayed on the minor coat proteins of the M13 phage termini by genetically engineering them to interact with the GNPs” (see, e.g., Sawada, “Results and Discussion”, pg. 512).
Regarding claim 21 pertaining to the hydrogel comprising at least one polymer, Sawada teaches “The expressed phages were purified by precipitation and redispersion procedures in the presence of high concentrations of PEG and NaCl (concentrations are 5% (w/v) and 2.5M, respectively)” (see, e.g., Sawada, “Experimental Procedures”, pg. 511). One of ordinary skill in the art would readily understand that PEG is a polymer.
Claim Rejections - 35 USC § 103, Obviousness
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 13 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Sawada as applied to claims 1-6, 9, 11, 16, and 21 above, and further in view of Jung (M13 Virus Aerogels as a Scaffold for Functional Inorganic Materials; 2017 – newly cited).
The teachings of Sawada are discussed above as it pertains to a hydrogel composition comprising cross-linked bacteriophages.
However, Sawada does not teach: wherein the hydrogel is dried to form an aerogel or xerogel (claim 13); or wherein the hydrogel composition excludes a polymer (claim 23).
Jung’s general disclosure relates to development of bulk 3D aerogels from M13 filamentous bacteriophages (see, e.g., Jung, abstract). Furthermore, Jung discloses “These ultralight porous structures demonstrate excellent mechanical properties with elastic behavior up to 90% compression. Furthermore, as the genome of M13 virus can be rationally engineered so that proteins on its capsid or ends can specifically bind to various inorganic materials, aerogels made from inorganic-complexed M13 structures with versatile functionalities are also developed. As examples for mono- and multi-component structures, M13-Ru and M13-CoFe2 O4 are explored in this work. This method enables the production of a wide variety of freestanding inorganic material aerogels with extensive opportunities for bio-scaffolds, energy storage, thermoelectrics, catalysis, hydrogen storage applications, etc., in the future” (see, e.g., Jung, abstract).
Regarding claim 13 pertaining to the hydrogel being dried to form an aerogel, Jung teaches “The suspension of M13 viruses at 0.015 wt% was dispersed in DI water using ultra bath sonication and concentrated by evaporating the DI water at 313 K. The 3D continuous gel network of M13 viruses was formed at 0.08 wt% and then the gel was transformed to M13 aerogel using freeze drying” (see, e.g., Jung, “Synthesis of M13 Virus Aerogel”, pg. 7).
Regarding claim 23 pertaining to the hydrogel excluding a polymer, Jung does not teach the presence of a polymer in the hydrogel composition (see, e.g., Jung, “Experimental Section: & whole document).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce Sawada’s hydrogel composition comprising cross-linked bacteriophages, wherein the hydrogel is dried to form an aerogel, as taught by Jung. One would have been motivated to do so because Jung teaches “The filamentous M13 viruses are widely used as a bio-template to assemble many different functional structures. In this work, based on its shape anisotropy, reasonable aspect ratio (length to diameter of ≈130), and low density, freestanding, bulk 3D aerogels are assembled from M13 for the first time. These ultralight porous structures demonstrate excellent mechanical properties with elastic behavior up to 90% compression. Furthermore, as the genome of M13 virus can be rationally engineered so that proteins on its capsid or ends can specifically bind to various inorganic materials, aerogels made from inorganic-complexed M13 structures with versatile functionalities” (see, e.g., Jung, abstract). Moreover, Sawada teaches “assemblies composed of M13 phages displaying gold-binding A3 peptides14 at the phage termini (A3 phages) and the GNPs (Figure 1) based on specific interactions between A3 peptides at the phage termini and the GNP surfaces, as well as the subsequent chemical crosslinking of the phages” (see, e.g., Sawada, Introduction, pg. 511). Therefore, based on the teachings of Sawada and Jung, it would have been obvious to produce a hydrogel comprising M13 filamentous phages, wherein the hydrogel is an aerogel, because this allows for production of ultralight porous structures demonstrate excellent mechanical properties with elastic behavior up to 90% compression. One would have expected success because Sawada and Jung both teach production of hydrogels with M13 bacteriophages.
Claims 15 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Sawada as applied to claims 1-6, 9, 11, 16, and 21 above, and further in view of Alvarez (Antibiotic-loaded silica nanoparticle-collagen composite hydrogels with prolonged antimicrobial activity for wound infection prevention; 2014 – cited in the IDS filed on 01/11/2022 – newly cited).
The teachings of Sawada are discussed above as it pertains to a hydrogel composition comprising cross-linked bacteriophages.
However, Sawada does not teach: wherein the hydrogel composition further comprises one or more molecules for cell targeting and/or infectivity (claim 15); or wherein the hydrogel composition further comprises a bioactive agent, wherein the bioactive agent is encapsulated within the hydrogel (claim 26).
Alvarez’s general disclosure relates to evaluation of silica-collagen type I nanocomposite hydrogels as medicated dressings for prevention of infection in chronic wounds (see, e.g., Alvarez, abstract). Moreover, Alvarez discloses encapsulation of gentamicin and rifamycin within plain silica nanoparticles in hydrogels to determine antimicrobial efficacy against Pseudomonas aeruginosa and Staphylococcus aureus (see, e.g., Alvarez, abstract). Alvarez discloses “Gentamicin release from the nanocomposites is sustained over 7 days, offering an unparalleled prolonged antibacterial activity. Particle immobilization also decreases their cytotoxicity towards surface-seeded fibroblast cells. Rifamycin-loaded 100 nm particles significantly alter the collagen hydrogel structure at high silica doses. The thus-obtained nanocomposites show no antibacterial efficiency, due to strong adsorption of rifamycin on collagen fibers” (see, e.g., Alvarez, abstract).
Regarding claims 15 and 26 pertaining to the molecule for infectivity and the bioactive agent, Alvarez teaches encapsulation of gentamicin and rifamycin, two antibiotics, within silica nanoparticles, wherein the loaded nanoparticles are immobilized in hydrogels to determine their antimicrobial efficacy against Pseudomonas aeruginosa and Staphylococcus aureus (see, e.g., Alvarez, abstract). One of ordinary skill in the art would readily understand that antibiotics target infectivity since they target infectious agents, such as bacteria.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce Sawada’s hydrogel comprising cross-linked bacteriophages, wherein the hydrogel also comprises antibiotics, as taught by Alvarez. One would have been motivated to do so because Alvarez teaches that antibiotics immobilized in hydrogels have prolonged antimicrobial activity, which allow for its design in biological dressings for prevention of wound infection (see, e.g., Alvarez, Section 4 – Conclusions, pg. 22). Moreover, Sawada teaches crosslinking of M13 phages and gold nanoparticles to produce crystalline hydrogels that can act as components of functional materials (see, e.g., Sawada, Introduction, pg. 511). Therefore, based on the teachings of Sawada and Alvarez, it would have been obvious to include a bioactive agent targeting infectivity, such as an antibiotic within the hydrogel because this allows for the hydrogel to exert antimicrobial properties against different bacteria and which can be used in wound dressings. One would have expected success because Sawada and Alvarez both teach hydrogel compositions.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Sawada as applied to claims 1-6, 9, 11, 16 and 21 above, and further in view of Dogic (Order phases of filamentous viruses; 2006 – newly cited).
The teachings of Sawada are discussed above as it pertains to a hydrogel composition comprising cross-linked bacteriophages.
However, Sawada does not teach: wherein the length of the filamentous is further turned through gene-modification, giving the phage-composed hydrogel structure colors (claim 18).
Dogic’s general disclosure relates to a review of “the equilibrium and non-equilibrium phase behavior of colloidal suspensions of rod-like viruses. It will treat the simplest case where the rods are the sole colloidal component and also the more complex phase behavior that arises in mixtures of binary rods and mixtures of rods with spherical colloids, or with polymers:” (see, e.g., Dogic, abstract). Moreover, Dogic discloses that “genetic engineering allows the systematic modification of the most important physical properties of the virus such as its length and charge per unit length” (see, e.g., Dogic, Section 3, pg. 48)
Regarding claim 18 pertaining to tuning the length via gene modification, Dogic teaches that genetic engineering allows for modification of virus length (see, e.g., Dogic, Section 3, pg. 48). Moreover, Dogic teaches the development of bacteriophages with different lengths using genetic engineered in order to make M13 viruses longer or shorter than the wild type, wherein the length can vary from 0.39 µm to 1.2 µm (see, e.g., Dogic, Section 3.1, pages 48-49). Furthermore, manipulation of the length of the bacteriophage via gene modification would inherently result in giving the phage-composed hydrogel structure colors (see, e.g., MPEP 2112.01(I)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce Sawada’s hydrogel comprising M13 bacteriophages, wherein the length of the bacteriophage is genetically modified, as taught by Dogic. One would have been motivated to do so because Dogic teaches that liquid crystalline behavior of phages can be altered based on virus length and surface charge (see, e.g., Dogic, section 3.2, pgs. 49-50). Furthermore, Sawada teaches the crystalline assembly of M13 phages and gold nanoparticles (see, e.g., Sawada, Introduction, pg. 511). Therefore, based on the teachings of Sawada and Dogic, it would have been obvious to genetically manipulate the length of the M13 phages in order to alter the crystalline behavior and properties of the produced hydrogel structure. One would have expected success because Sawada and Dogic both teach crystalline structures produced with M13 bacteriophages.
Claims 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Sawada as applied to claims 1-6, 9, 11, 16, and 21 above, and further in view of Souza (Networks of gold nanoparticles and bacteriophages as biological sensors and cell-targeting agents; 2006 – cited in the IDS filed on 01/11/2022 – previously cited).
The teachings of Sawada are discussed above as it pertains to a hydrogel composition comprising cross-linked bacteriophages.
Regarding claims 19-20 pertaining to the bacteriophage strains, Sawada teaches M13 bacteriophages, which are filamentous, Escherichia coli bacteriophages (see, e.g., Sawada, Introduction, pg. 511 & “Experimental Procedures”, pg. 511).
However, Sawada does not teach: a second different bacteriophage strain (claim 19); or wherein the second bacteriophage strain targets the same or different bacterial species to treat complex infections (claim 20).
Souza’s general disclosure relates to the “fabrication of spontaneous, biologically active molecular networks consisting of bacteriophage (phage) directly assembled with gold (Au) nanoparticles (termed Au-phage)” (see, e.g., Souza, abstract). Moreover, Souza discloses that filamentous bacteriophage are resistant to hash conditions such as high salt concentrations, acidic pH, chaotropic agents, and prolonged storage (see, e.g., Souza, Introduction, pg. 1215).
Regarding claims 19 and 20 pertaining to the second different bacteriophage strain, Souza teaches an fd phage (see, e.g., Souza, “Au-Phage Synthesis and Quantification”, pg. 1219), which is an E. coli bacteriophage.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the M13 bacteriophage within a hydrogel, as taught by Sawada, with the fd phage, as taught by Souza. One would have been motivated to do so because Souza teaches that the fd phage is more anionic than M13, but that both fd and M13 phage particles act as “polyanionic particles in solution with several negative surface charges associated with each of the ~2,700 copies of the major capsid protein”, which allows for phage bundles to form using like-charge attraction (see, e.g., Souza, “Results and Discussion”, pg. 1217). Additionally, Souza teaches that filamentous bacteriophage are resistant to hash conditions such as high salt concentrations, acidic pH, chaotropic agents, and prolonged storage (see, e.g., Souza, Introduction, pg. 1215). Moreover, Sawada teaches “M13 phages act as components for use in the construction of viral materials for electronics, biodevices and sensors.4–7 In these cases, molecular recognition capabilities are derived from the displayed foreign peptides, which specifically bind to artificial materials and have an important role in regularly assembled phage structures. Significantly, surface modification of M13 phages has been established through genetic engineering8 and synthetic chemical9 methods. Therefore, M13 phages are regarded as potential components of assembled nanomaterials” (see, e.g., Sawada, Introduction, pg. 511). Therefore, based on the teachings of Sawada and Souza, it would have been obvious to combine two different filamentous bacteriophages because both phages target the same bacteria (i.e., E. coli) and both can be assembled within nanomaterials. One would have expected success because Sawada and Souza both teach the production of hydrogels containing filamentous bacteriophages.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Sawada as applied to claims 1-6, 9, 11, 16, and 21 above, and further in view of Garcia (Methods of Producing Microstructured Hydrogels for Targeted Applications in Biology; 2019 – newly cited).
The teachings of Sawada are discussed above as it pertains to a hydrogel composition comprising cross-linked bacteriophages.
However, Sawada does not teach: microstructures of the surface of the hydrogel composition (claim 14).
Garcia’s general disclosure relates to a review of “the more commonly used polymers, chemistries, and methods for generating microstructures in biomaterials, highlighting the range of possible morphologies that can be produced, and the limitations of each method. With a focus in liquid-liquid phase separation, methods and chemistries well suited for stabilizing the interface and arresting the phase separation are covered” (see, e.g., Garcia, abstract).
Regarding claim 24 pertaining to microstructures on the surface of the hydrogel composition, Garcia teaches the production of hydrogels with microstructures on the surface, such as “micron-size particles in a polymer solution for further crosslinking, with the microparticles entrapped in the resulting hydrogel” (see, e.g., Garcia, Section 2.1, pg. 4). Furthermore, Garcia teaches “photopatterning methods (employing photomasks and photocrosslinkable polymers) allow the creation of a wide variety of structures that will conform to the overall shape of the hydrogel” (see, e.g., Garcia, Section 2.2, pg. 4). Moreover, Garcia teaches “The use of laser lithography methods provides significant flexibility in the production of microstructured materials, as depending on the wavelength and intensity of the laser light, photopolymerization of hydrogel precursors or photoablation of hydrogels can be performed. UV laser photopatterning is used for creating microstructures by ablation of hydrogels [101]. These approaches, however, are useful only for patterning the surface of the material or for eroding microchannels, because the laser ablates everything in its path and only 2D patterns with a projection in a third dimension are thus possible” (see, e.g., Garcia, Section 2.3, pg. 5). Additionally, Garcia teaches “In microfluidics approaches, which have been employed to generate a wide variety of shaped microparticles with myriad compositions, non-miscible liquids are injected through interconnected micron-size channels; the incompatibility drives the formation of a liquid microstructure inside the dispersing phase. Subsequent polymerization by external sources, such as light, or due to the interactions between the liquids, such as ionic polymers in the presence of multivalent ions, yields the formation of microgels [116]. This is one of the methods for generating pre-shaped microhydrogels that can be dispersed later in hydrogel precursors to form a microstructured hydrogel in which all phases are hydrogel in composition” (see, e.g., Garcia, Section 2.4, pg. 6). Therefore, Garcia teaches multiple methods by which microstructures can be introduced on the surface of the hydrogel composition.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce Sawada’s hydrogel composition comprising cross-linked M13 bacteriophages, wherein the hydrogel comprises microstructures on the surface, as taught by Garcia. One would have been motivated to do so because Garcia teaches that introduction of microstructures on the surface of the hydrogel increases the mechanical strength of the hydrogel (see, e.g., Garcia, Section 2.1, pg. 4). Moreover, Sawada teaches the crosslinking of M13 bacteriophages and gold nanoparticles, wherein functional molecules could be conjugated to the surface of the hydrogel in order to produce functionalized assemblies, and which can be exploited in materials science and technology (see, e.g., Sawada, Conclusions, pg. 515). Therefore, based on the teachings of Sawada and Garcia, it would have been obvious to produce a hydrogel with microstructures in order to increase the mechanical strength of the hydrogel, which can further be used in materials science and technology. One would have expected success because Sawada and Garcia both teach production of hydrogels.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Sawada as applied to claims 1-6, 9, 11, 16, and 21 above, and further in view of Suzuki (Polymeric hydrogel microspheres: design, synthesis, characterization, assembly and applications; 2017 – previously cited).
The teachings of Sawada are discussed above as it pertains to a hydrogel composition comprising cross-linked bacteriophages.
However, Sawada does not teach: the hydrogel composition further for transferring to microgels (claim 25).
Suzuki’s general disclosure relates to “Hydrogel microspheres (microgels), which consist of crosslinked hydrophilic or amphiphilic polymer chains, are components of stable colloidal dispersions” (see, e.g., Suzuki, abstract). Moreover, Suzuki discloses the “synthesis, characterization, assembly, and application” of hydrogel microspheres (microgels) and their promising prospects for advanced chemical technologies, such as drug carriers (see, e.g., Suzuki, abstract).
Regarding claim 25 pertaining to microgels, Suzuki teaches microgels that are covered with a thin hydrogel layer (see, e.g., Suzuki, “Nanocomposite microgels: synthesis and properties”, pg. 696).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the hydrogel composition comprising cross-linked bacteriophages, as taught by Sawada, to a microgel, as taught by Suzuki. One would have been motivated to do so because Suzuki teaches that microgels have advanced chemical technologies, such as drug carriers (see, e.g., Suzuki, abstract), as well as pre-existing applications, such as in coatings and cosmetics (see, e.g., Suzuki, “Concluding Remarks”, pg. 700). Moreover, Sawada teaches that “Assemblies composed of M13 phages and GNPs give rise to novel opportunities for the construction of regular assemblies as components of functional materials” (see, e.g., Sawada, Introduction, pg. 511). Therefore, based on the teachings of Sawada and Suzuki, it would have been obvious to transfer the hydrogel into a microgel because this would allow for the microgel to be used in functional materials, such as for advanced chemical properties, such as drug carriers. One would have expected success because Sawada and Suzuki both teach hydrogel compositions.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Sawada as applied to claims 1-6, 9, 11, 16, and 21 above, and further in view of Ajji (Production of hydrogel wound dressings using gamma radiation; 2005 – previously cited).
Ajji’s general disclosure relates to hydrogel wound dressing prepared using a gamma ray
irradiation technique for sterilization (see, e.g., Ajji, abstract).
Regarding claim 28 pertaining to a wound dressing, Ajji teaches that hydrogels can be
used as wound dressings and that there are “some commercialized hydrogel wound dressings
under the trade names Vigilon, Ivalon, Aqua gel and Kik gel” (see, e.g., Ajji, Introduction, pg.
375).
It would have been obvious to one of ordinary skill in the art before the effective filing
date of the claimed invention to apply the M13 bacteriophage cross-linked hydrogel composition, as taught by Sawada, to a wound dressing, as taught by Ajji. One would have been motivated to do so because Ajji teaches that hydrogels as wound dressings can absorb fluids effectively, are pleasant in touch and painless in removal, exhibit high elasticity and good mechanical strength, have good transparency, and can act as a barrier against microbes (see, e.g., Ajji, Introduction, pg. 376). Moreover, Sawada teaches that M13 phages and gold nanoparticles crosslink to form a liquid crystal formation, resulting in the formation of hydrogels (see, e.g., Sawada, Conclusions, pg. 515). Therefore, based on the teaching of Sawada and Ajji, it woul have been obvious to produce a wound dressing based on the hydrogel composition taught by Sawada because of the advantageous properties exhibited by hydrogels, such as absorption of fluids, painless to touch and remove, high elasticity, good mechanical strength, good transparency, and barrier against microbes. One would have expected success because Sawada and Ajji both teach hydrogel compositions
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 1-4 and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 19, 21-23, and 26 of copending Application No. 18/696,755 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because App’755 teaches a hydrogel composition with microstructures (see, e.g., App’755, claims 1 and 26), wherein the hydrogel further comprises bacteriophages (see, e.g., App’755, claim 19), wherein the bacteriophages self-assemble into bundles (see, e.g., App’755, claim 21), wherein the bacteriophages comprise filamentous bacteriophages (see, e.g., App’755, claim 22), and wherein the bacteriophages comprise Escherichia coli bacteriophages, such as f1, M13, or combination thereof (see, e.g., App’755, claim 23).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Examiner’s Response to Arguments
Regarding Applicant’s arguments pertaining to the previous 35 U.S.C. 102 and 103 rejections in view of Peivandi (remarks, page 5), as previously mentioned, all previous 102 and 103 rejections have been withdrawn; however, new grounds of rejection are set forth above. Moreover, Peivandi was not relied in the newly presented 35 U.S.C. 102 rejection. Therefore, Applicant’s arguments are moot.
In response to Applicant’s argument that the double patenting rejection be held in abeyance (remarks, page 6), the Office does not hold any rejections in abeyance. All rejections are maintained until Applicant overcomes them by amendment(s) or files a terminal disclaimer. Therefore, the nonstatutory double patenting rejection is maintained.
Art of Record
Sawada, “Controlled release of antibody proteins from liquid crystalline hydrogels composed of genetically engineered filamentous viruses”. Mater. Chem. Front., 2017,1, 146-151
Conclusion
Claims 1-6, 9, 11, 13, 15-16, 18-21, 23-26, and 28 are rejected.
No claims are allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
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/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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