DETAILED ACTION
Receipt is acknowledged of applicant’s Amendment/Remarks filed 9/25/2025.
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 .
Status of the Claims
Claims 13-26, 37-42 and 50-52 have been amended. Claims 1-12, 27-36 and 43-49 are cancelled. No claims are newly added. Accordingly, claims 13-26, 37-42 and 50-52 remain pending in the application. Claims 24, 37-40 and 50-52 stand withdrawn from further consideration, without traverse. Claims 13-23, 25, 26, 41 and 42 are currently under examination.
Withdrawn Objections/Rejections
Applicant’s amendment renders the objection of claim 26 moot. Specifically, the claim has been amended to delete the limitation, “of any one”. Thus, said objection has been withdrawn.
Applicant’s amendment renders the rejection of claim 15 under 35 USC 112(b) moot. Specifically, the term “substantially” has been deleted from the claim. Thus, said rejection has been withdrawn.
Maintained Rejections
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.
Claims 13-15, 17-18, 26 and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Curtin et al. (US 2009/0191254 A1, Jul. 30, 2009, hereafter as Curtin) in view of Gorecka et a. (WO 2015/063015 A1, May 7, 2015, hereafter as “Gorecka”) and Henrotin et al. (US 2012/0315307 A1, Dec. 13, 2012, hereafter as “Henrotin”) as evidenced by Coloplast (see PTO-892).
The claims are drawn to a medical implant assembly, comprising a medical implant (elected species = “orthopedic device”) and a time release anti-bacterial composition applied to at least a portion of at least one surface of the medical implant/incorporated therein, wherein the time release anti-bacterial composition comprises: a hydrogel; alginate beads embedded within the hydrogel; and a bacteriophage cocktail encapsulated within the alginate beads, the bacteriophage cocktail comprising: (i) at least one E. coli bacteriophage; and (ii) at least one Klebsiella pneumoniae bacteriophage. Applicant elected “orthopedic device” as the medical implant species.
Regarding instant claims 13, 26 and 41, Curtin teaches medical device coatings comprising one or more bacteriophages and a carrier for the purpose of inhibiting formation of a bacterial biofilm and thereby reducing risk of infection (abstract; [0006]-[0008], [0060]). Curtin teaches the particular bacteriophages that inhibit, Klebsiella pneumoniae and Escherichia coli ([0061]). Curtin also teaches the particular carrier, a hydrogel ([0060]). Curtin further teaches medical devices comprising said coatings and also teaches the particular medical devices, prosthetic joints and orthopedic implants (abstract; [0007] and [0045]) as well as incorporating the bacteriophage compositions into a cement mixture ([0078]).
Curtin is silent to the particular combination of Klebsiella pneumoniae and Escherichia coli (instant claims 26 and 41).
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to combine the particular bacteriophages, Klebsiella pneumoniae and Escherichia coli with a reasonable expectation of success because Curtin expressly teaches a finite group of bacteriophages that are suitable as well as combinations of said bacteriophages. Further, "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose” (MPEP 2144.06(I)).
Curtin is silent to bacteriophages encapsulated within alginate beads (instant claims 26 and 41), or more specifically sodium alginate beads (instant claim 13).
Gorecka teaches methods of encapsulating a biological material including bacteriophages, a therapeutically active substance, cells, and so on (page 1, lines 4-5; page 6, lines 14-18). In a particular embodiment, Gorecka teaches encapsulating bacteriophages with a polymer, wherein the polymer is alginate, preferably sodium alginate (page 7, lines 11-16). Gorecka teaches that the encapsulated bacteriophages are useful in the treatment of bacterial infection (page 10, lines 2-3). Gorecka also teaches that said encapsulation demonstrates good retention of the encapsulated material (page 5, lines 24-25).
Curtin and Gorecka are drawn to compositions comprising bacteriophages for treating/reducing the risk of infection, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to encapsulate the bacteriophages into alginate beads such as sodium alginate beads into the invention of Curtin as suggested by Gorecka with a reasonable expectation of success. One of ordinary skill would have been motivated to do so because Gorecka teaches that encapsulation of bacteriophages in alginate beads are an effective delivery mode of bacteriophages and said encapsulation demonstrates good retention of the encapsulated material for the purpose of reducing bacterial infection.
Curtin and Gorecka are silent to alginate beads embedded in the hydrogel (instant claims 26 and 41).
Henrotin teaches an implantable composition comprising chitosan/alginate beads comprising chondrocytes, said beads embedded in a chitosan hydrogel ([0036]). Henrotin teaches that the biodegradable nature of the implant ensures a progressive resorption after implantation ([0090]).
Curtin and Henrotin are both drawn to compositions comprising hydrogel carriers for biological materials and Gorecka and Henrotin are drawn to encapsulated compositions comprising alginate beads and a biological material encapsulated therein, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to incorporate the alginate beads into the hydrogel as suggested by Henrotin with a reasonable expectation of success. One of ordinary skill would have been motivated to do so because Henrotin teaches encapsulation of biological materials within chitosan/alginate beads embedded in a hydrogel is an effective mode of delivery of biological materials and the combination of degradable beads and degradable hydrogel carrier allows for tunable release of the biological material.
Regarding the limitation, “time release” (instant claims 26 and 41), Curtin teaches that the bacteriophage is releasable from a carrier/coating material ([0048] and [0060]) and Gorecka and Henrotin, as discussed above, suggest alginate beads in a hydrogel carrier. Gorecka also teaches a particular embodiment wherein bacteriophages are encapsulated with a polymer, wherein the polymer is alginate (page 7, lines 11-16). Gorecka also teaches that the encapsulated material is releasable (page 8, lines 27-30). Henrotin teaches a biodegradable implantable composition comprising chitosan/alginate beads comprising chondrocytes, said beads embedded in a chitosan hydrogel ([0036] and [0090]).
While the references do not explicitly teach a time release composition, it is noted that the instant specification states, “the alginate beads provide a time release mechanism to the coating, as the beads are stable (i.e., do not melt) at room temperature but will provide gradual release of the bacteriophage as the temperature of the hydrogel increases to body temperature” ([0041]). MPEP 2112.01(I) states,
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product.
In the instant case, Curtin, Gorecka and Henrotin suggest the claimed anti-bacterial coating composition including the alginate beads which are indicated in the instant specification as the structure that provides the function of a time release mechanism. The claimed and prior art products are identical or substantially identical in structure or composition, thus, a prima facie case of obviousness has been established. A skilled artisan would reasonably expect that the identical or substantially identical structure would yield the same characteristics including time release.
Regarding instant claim 14, Gorecka further teaches alginate microcapsules coated with chitosan was known (page 2, lines 19-21 and 26-27 and page 3, lines 1-5) and exemplifies alginate microcapsules having a chitosan coating (page 14, line 15 – page 15, line 7). While Gorecka teaches that such an embodiment was less efficient (page 15, lines 8-9), a known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use (MPEP 2123 (II)). It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to include a chitosan coating on the alginate beads with a reasonable expectation of success because Gorecka teaches that alginate beads coated with chitosan is a known technique suitable for microencapsulation of bacteriophages.
Regarding instant claim 15, Gorecka further teaches drying (dehydrating) the microcapsules by lyophilization, air drying, desiccation or freeze-drying and selection of a drying method is based on drying without adversely affecting the properties of the encapsulated material (page 6, lines 6-9). It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to include substantially dehydrated alginate beads with a reasonable expectation of success because Gorecka teaches that drying alginate beads is a known technique suitable for microencapsulation of bacteriophages.
Regarding the limitation, “are substantially rehydrated upon exposure to bodily fluid”, said limitation is considered a future intended step that would occur during normal use when the coating composition is coated on a medical device and implanted within the body. Thus, such a limitation does not show a patentable distinction.
Regarding instant claims 17 and 18, Curtin further teaches that the hydrogel coating can further include an antimicrobial agent or another antibiotic, such as silver ([0064] and [0084]). Silver is a well-documented antimicrobial, that has been shown to kill bacteria, fungi and certain viruses (i.e., anti-bacterial, anti-fungal, anti-viral) as evidenced by Coloplast. It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to further include an anti-microbial agent such as the anti-fungal agent, silver, with a reasonable expectation of success because Curtin teaches that including silver in the hydrogel that is coated on medical devices imparts additional anti-microbial/anti-fungal properties that further reduce the risk of infection.
Thus, the combined teachings of Curtin, Gorecka and Henrotin render the instant claims prima facie obvious.
Response to Arguments
Applicant's arguments, filed 9/25/2025, regarding the 103 rejection over Curtin, Gorecka and Henrotin have been fully considered but they are not persuasive.
Applicant argues that there are significant differences in the manner in which Curtin used the bacteriophages as compared to the bacteriophages that are used in the invention described and claimed in this application. Remarks, page 9.
In response, it is respectfully submitted that the claims are drawn to products and not a method of using said products. Further, any intended use recitation in a product claim does not alone show patentable distinction. A recitation of intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. In other words, if the prior art structure is capable of performing the intended use, then it meets the claim. Additionally, it is noted that Curtin teaches medical device coatings comprising one or more releasable bacteriophages and a carrier for the purpose of inhibiting formation of a bacterial biofilm and thereby reducing risk of infection and the instant invention is drawn to a medical implant assembly comprising a medical implant having a time release anti-bacterial coating composition comprising a hydrogel, alginate beads embedded within the hydrogel and particular bacteriophages encapsulated within the alginate beads. Accordingly, Curtin and the claimed invention are both drawn to medical devices having a composition comprising bacteriophages for the same purpose of inhibiting bacteria/reducing the risk of infection. As such, Curtin is relevant prior art to the claimed invention. Applicant’s argument is unpersuasive.
Applicant argues that Gorecka is focused on the alginate encapsulation to protect bacteriophages that are consumed and does not teach or suggest the use of the bacteriophage in conjunction with a coating of a medical device. Applicant asserts there is no need for the alginate encapsulated bacteriophage to be embedded in a hydrogel that would facilitate retaining the alginate encapsulated bacteriophage on the surface of the medical device. Applicant also argues that Gorecka does not teach or suggest a time release anti-bacterial coating composition. Remarks, pages 9-10.
In response, it is respectfully submitted that while Gorecka does not teach a bacteriophage in combination with a medical device, Curtin teaches said combination and, thus, Gorecka is not relied upon for said combination. However, Gorecka is relied upon for its teaching of encapsulating bacteriophages within alginate beads. Gorecka teaches that the encapsulated bacteriophages are useful in the treatment of bacterial infection (page 10, lines 2-3). Gorecka also teaches that said encapsulation demonstrates good retention of the encapsulated material (page 5, lines 24-25). The excerpt of Gorecka that Applicant points to starting at page 8, line 22 of Gorecka, it is stated, “Encapsulation also protects the encapsulated material from degradation during storage… the encapsulated material is released at neutral pH… microcapsules comprising alginate and chitosan in accordance with the invention protect encapsulated material during drying steps to maintain integrity and viability of the encapsulated material”. Accordingly, Gorecka provides motivation as to why a skilled artisan would apply the teachings of Gorecka to other biomedical purposes. MPEP 2123 states that references are relevant as prior art for all they contain and a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art. The teachings of Gorecka would have reasonably suggested to a skilled artisan that alginate encapsulation of bacteriophages is useful in protecting bacteriophages from degradation during processing and in storage as well as releasable at a neutral pH. Regarding time release, Gorecka, as stated above, teaches that the bacteriophages are releasable from the alginate beads/capsules. Further, the instant specification states, “the alginate beads provide a time release mechanism to the coating, as the beads are stable (i.e., do not melt) at room temperature but will provide gradual release of the bacteriophage as the temperature of the hydrogel increases to body temperature” ([0041]). MPEP 2112.01(I) states,
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product.
In the instant case, Curtin, Gorecka and Henrotin suggest the claimed anti-bacterial coating composition including the alginate beads which are indicated in the instant specification as the structure that provides the function of a time release mechanism. The claimed and prior art products are identical or substantially identical in structure or composition, thus, a prima facie case of obviousness has been established. A skilled artisan would reasonably expect that the identical or substantially identical structure would yield the same characteristics including time release. Accordingly, the limitation “time release” is met by the teachings of the prior art. Applicant’s arguments are not persuasive.
Applicant also argues that Henrotin teaches chitosan/alginate beads as carriers for mammalian cells. Henrotin is concerned with cartilage tissue engineering and not phage delivery. Applicant asserts that the function of Henrotin is entirely different – cell culture vs. infection control and, as such, Henrotin is non-analogous art and inappropriate to cite in rejecting the instant claims. Remarks, page 11.
In response, it is respectfully submitted that MPEP 2141.01(a) states,
In order for a reference to be proper for use in an obviousness rejection under 35 U.S.C. 103, the reference must be analogous art to the claimed invention. In re Bigio, 381 F.3d 1320, 1325, 72 USPQ2d 1209, 1212 (Fed. Cir. 2004). A reference is analogous art to the claimed invention if: (1) the reference is from the same field of endeavor as the claimed invention (even if it addresses a different problem); or (2) the reference is reasonably pertinent to the problem faced by the inventor (even if it is not in the same field of endeavor as the claimed invention).
Henrotin teaches an implantable composition comprising chitosan/alginate beads comprising chondrocytes, said beads embedded in a chitosan hydrogel ([0036]). Henrotin teaches that the biodegradable nature of the implant ensures a progressive resorption after implantation ([0090]). While Henrotin is not drawn to bacteriophages as the encapsulated material, Henrotin teaches encapsulation of biological material in chitosan/alginate beads which are further embedded in a chitosan hydrogel and explains that such a formulation provides a progressive resorption after implantation. Both the reference and the claimed invention are drawn to encapsulation of a biological material that is administered and released in the body. Accordingly, Henrotin is considered to be from the same field of endeavor as the claimed invention. It is also noted that
MPEP 2123 states that references are relevant as prior art for all they contain and a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art. The teachings of Henrotin would have reasonably suggested to a skilled artisan that the biodegradable nature of the alginate beads embedded in a chitosan hydrogel ensures a progressive resorption after implantation. It is further noted that with respect to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The instant rejection is based on the combined teachings of Curtin, Gorecka and Henrotin and said rejection sets out a proper prima facie case of obviousness. Thus, Applicant’s arguments are not persuasive.
Applicant further argues that there is no motivation to combine the references as contended and asserts that the Examiner has not shown why a skilled artisan would combined a tissue-engineering bead reference with a catheter coating reference to arrive at the multi-level phage encapsulation that is described in the claimed invention. Remarks, page 11.
In response, it is respectfully submitted that the instant rejection is based on the combined teachings of Curtin, Gorecka and Henrotin. Curtin is relied upon for its teaching of medical devices and coatings thereon comprising one or more bacteriophages and a carrier. Gorecka is relied upon for its teaching of encapsulation of biological materials such as bacteriophages (as well as cells) within alginate microcapsules (beads). Both Curtin and Gorecka are drawn to compositions comprising bacteriophages for treating/reducing the risk of infection and Gorecka provides the motivation to modify Curtin because Gorecka teaches that encapsulation of bacteriophages in alginate beads are an effective delivery mode of bacteriophages and said encapsulation demonstrates good retention of the encapsulated material for the purpose of reducing bacterial infection. Henrotin is relied upon for its teaching of alginate beads within a hydrogel. Henrotin is drawn to an implantable composition comprising chitosan/alginate beads comprising chondrocytes (cells), said beads embedded in a chitosan hydrogel. Curtin and Henrotin are both drawn to compositions comprising hydrogel carriers for biological materials and Gorecka and Henrotin are drawn to encapsulated compositions comprising alginate beads and a biological material encapsulated therein. Henrotin provides the motivation to modify Curtin/Gorecka because Henrotin teaches that the biodegradable nature of the implantable alginate beads within a hydrogel ensures a progressive resorption after implantation. Thus, contrary to Applicant’s assertions, the rejection explains the motivation and rationale as to why a skilled artisan would have combined the references including a tissue-engineering bead reference with a medical device coating reference. A proper prima facie case has been established.
Thus, for these reasons, Applicant’s arguments are found unpersuasive. Said rejection is maintained.
Claim 42 stands rejected under 35 U.S.C. 103 as being unpatentable over Curtin et al. (US 2009/0191254 A1, Jul. 30, 2009, hereafter as Curtin) in view of Gorecka et al. (WO 2015/063015 A1, May 7, 2015, hereafter as “Gorecka”) and Henrotin et al. (US 2012/0315307 A1, Dec. 13, 2012, hereafter as “Henrotin”), as applied to claim 41 above, and further in view of Manohar et al. “Therapeutic Characterization and Efficacy of Bacteriophage Cocktails Infecting Escherichia coli, Klebsiella pneumoniae, and Enterobacter Species”. Front. Microbiol. 10:574 (2019), pp. 1-12; hereafter as “Manohar”).
The claimed invention is described above.
Curtin, Gorecka, and Henrotin teach the elements discussed above.
Regarding instant claim 42, Curtin further teaches lytic bacteriophages are particularly suitable for the invention ([0042] and [0063]).
Curtin, Gorecka, and Henrotin are silent to E. coli bacteriophages and Klebsiella pneumoniae bacteriophages that are Caudovirales lytic bacteriophages.
Manohar teaches that infection due to antibiotic resistant bacteria are increasing globally and alternative therapies such as phage therapy is a potentially effective treatment (abstract; conclusion). Manohar teaches a cocktail comprising the three bacteriophages, Escherichia virus myPSH2311 infecting E. coli, Klebsiella virus myPSH1235 infecting K. pneumoniae, and Enterobacter virus myPSH1140 infecting four different species of Enterobacter exhibited broad host range activity and reduced bacterial load from 106 to 103 CFU/mL within 2 hours (abstract). Said phages belong to the order Caudovirales that are lytic phages (page 9, right col.).
Curtin, Gorecka and Manohar are drawn to compositions comprising bacteriophages for treating/reducing the risk of infection, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to include E. coli bacteriophages and Klebsiella pneumoniae bacteriophages that are Caudovirales lytic bacteriophages into the invention of Curtin/Gorecka/Henrotin as suggested by Manohar with a reasonable expectation of success. One of ordinary skill would have been motivated to do so because Curtin generally teaches the inclusion of bacteriophages that inhibit Klebsiella pneumoniae and Escherichia coli as well as lytic bacteriophages for the purpose of reducing the risk of/treating infections and Manohar specifically teaches a cocktail of Caudovirales lytic bacteriophages that effectively inhibit E. coli and Klebsiella pneumoniae and has the potential to treat infection due to antibiotic resistant bacteria.
Thus, the combined teachings of Curtin, Gorecka, Henrotin and Manohar render the instant claim prima facie obvious.
Response to Arguments
Applicant's arguments, filed 9/25/2025, regarding the 103 rejection over Curtin, Gorecka, Henrotin and Manohar have been fully considered but they are not persuasive.
Applicant relies on the same arguments as presented for the 103 rejection over Curtin, Gorecka and Henrotin. No further arguments regarding claim 42 are presented. Remarks, page 12.
For the same reasons as discussed above, Applicant’s arguments are not persuasive.
Thus, said rejection is maintained.
Claim 16 stands rejected under 35 U.S.C. 103 as being unpatentable over Curtin et al. (US 2009/0191254 A1, Jul. 30, 2009, hereafter as Curtin) in view of Gorecka et al. (WO 2015/063015 A1, May 7, 2015, hereafter as “Gorecka”) and Henrotin et al. (US 2012/0315307 A1, Dec. 13, 2012, hereafter as “Henrotin”), as applied to claim 41 above, and further in view of Ferullo et al. (WO 2017015652 A1, Jan. 26, 2017, hereafter as “Ferullo”).
The claimed invention is described above.
Curtin, Gorecka, and Henrotin teach the elements discussed above.
Curtin, Gorecka, and Henrotin are silent to a detectable label that indicates when bacteria are present and encounter the bacteriophage cocktail.
Ferullo teaches treating Staphylococcus infections, including prosthetic joint infections, particularly by removing biofilms utilizing bacteriophages (abstract; page 2, lines 6-10). Ferullo also teaches that the bacteriophage may be engineered to encode one or more markers whose expression will aid in detection of susceptible bacteria in a sample and positive identification will further allow for treating the presence of the targeted bacteria (page 3, lines 16-22; page 13, lines 5-24; page 16, line 15 – page 17, line 18). It is also noted that Ferullo teaches the specific detectable marker, green fluorescent proteins (page 13, line 11), which is the named label/marker in the instant specification at [0057].
Curtin, Gorecka and Ferullo are drawn to compositions comprising bacteriophages for treating/reducing the risk of infection, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to include a detectable label such as green fluorescent proteins into the invention of Curtin/Gorecka/Henrotin as suggested by Ferullo with a reasonable expectation of success. One of ordinary skill would have been motivated to do so because Ferullo teaches that bacteriophages engineered to encode one or more markers effectively aid in detection of susceptible bacteria and selectively treat the targeted bacteria with the bacteriophage.
Thus, the combined teachings of Curtin, Gorecka, Henrotin and Ferullo render the instant claim prima facie obvious.
Response to Arguments
Applicant's arguments, filed 9/25/2025, regarding the 103 rejection over Curtin, Gorecka, Henrotin and Ferullo have been fully considered but they are not persuasive.
Applicant relies on the same arguments as presented for the 103 rejection over Curtin, Gorecka and Henrotin. No further arguments regarding claim 16 are presented. Remarks, page 12.
For the same reasons as discussed above, Applicant’s arguments are not persuasive.
Thus, said rejection is maintained.
Claim 19 stands rejected under 35 U.S.C. 103 as being unpatentable over Curtin et al. (US 2009/0191254 A1, Jul. 30, 2009, hereafter as Curtin) in view of Gorecka et al. (WO 2015/063015 A1, May 7, 2015, hereafter as “Gorecka”) and Henrotin et al. (US 2012/0315307 A1, Dec. 13, 2012, hereafter as “Henrotin”), as applied to claim 41 above, and further in view of Malik et al. (“Formulation, stabilization and encapsulation of bacteriophage for phage therapy”, Advances in Colloid and Interface Science, Volume 249, November 2017, Pages 100-133; hereafter as “Malik”).
The claimed invention is described above.
Curtin, Gorecka, and Henrotin teach the elements discussed above. It is noted that Curtin teaches that the hydrogel is defined as “a colloid in which a solid disperse phase (for example, macromolecules such as collagen, gelatin, agarose, acrylamide, starch, or the like) forms a network in combination with the fluid continuous phase, and the fluid is water” ([0053]) and Henrotin teaches the particular hydrogel carrier, chitosan ([0088]).
Curtin, Gorecka, and Henrotin are silent to the hydrogel comprising pectin.
Malik is drawn to phage therapy for the treatment of bacterial infection (abstract). Malik teaches that microbial biofilms on medical devices e.g. urinary and central venous catheters, stents, implants, invasive health monitoring devices, are a significant healthcare problem and are responsible for a vast majority of medical device associated infections (page 125, section 4.11). Malik also teaches that studies on phage encapsulation have used a variety of hydrophilic and hydrophobic polymers including agarose, alginate, chitosan, pectin, etc. and in different morphologies including spheres and membranes (page 118, section 4.7). Malik teaches that triggers for phage release include polymer solvation, polymer dissolution and erosion, polymer hydrolysis, phase inversion induced by temperature, and pH triggered dissolution of polymer and enzyme driven polymer degradation (page 118, section 4.7). Malik further acknowledges that pectin forms a gel via crosslinking (page 120, right col, 2nd para.).
Curtin, Gorecka and Manohar are drawn to compositions comprising bacteriophages for treating/reducing the risk of infection, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to include or substitute pectin in the hydrogel of Curtin/Gorecka/Henrotin as suggested by Malik with a reasonable expectation of success. One of ordinary skill would have been motivated to do so because Curtin generally teaches the inclusion of bacteriophages in a hydrogel carrier (such as collagen, gelatin, agarose, acrylamide, starch, or the like) for the purpose of reducing the risk of/treating infections, Henrotin teaches chitosan as a particular hydrogel carrier for the delivery of biological materials, and Malik specifically teaches that pectin along with other gellable carriers (chitosan, agarose, etc.) are suitable carriers for bacteriophages in the treatment of bacterial infections. It is prima facie obvious to combine or substitute equivalents known for the same purpose (MPEP 2144.06).
Thus, the combined teachings of Curtin, Gorecka, Henrotin and Malik render the instant claim prima facie obvious.
Response to Arguments
Applicant's arguments, filed 9/25/2025, regarding the 103 rejection over Curtin, Gorecka, Henrotin and Malik have been fully considered but they are not persuasive.
Applicant relies on the same arguments as presented for the 103 rejection over Curtin, Gorecka and Henrotin. No further arguments regarding claim 19 are presented. Remarks, page 13.
For the same reasons as discussed above, Applicant’s arguments are not persuasive.
Thus, said rejection is maintained.
Claims 20-21 stand rejected under 35 U.S.C. 103 as being unpatentable over Curtin et al. (US 2009/0191254 A1, Jul. 30, 2009, hereafter as Curtin) in view of Gorecka et al. (WO 2015/063015 A1, May 7, 2015, hereafter as “Gorecka”) and Henrotin et al. (US 2012/0315307 A1, Dec. 13, 2012, hereafter as “Henrotin”), as applied to claim 41 above, and further in view of Skurnik et al. (EP 3616730 A1, Mar. 4, 2020, hereafter as “Skurnik”).
The claimed invention is described above.
Curtin, Gorecka, and Henrotin teach the elements discussed above.
Curtin further teaches that the hydrogel is defined as “a colloid in which a solid disperse phase (for example, macromolecules such as collagen, gelatin, agarose, acrylamide, starch, or the like) forms a network in combination with the fluid continuous phase, and the fluid is water” ([0053]) and that the bacteriophage composition further comprises a growth or activity enhancing agent including agents that help stabilize or multiply bacteriophages, such as divalent metal cations (e.g., the divalent metal cation is Ca2+ or Mg2+, CaCl2 or MgCl2) ([0059], [0064]). Curtin also teaches that the presence of divalent cations in the growth medium appeared to increase the effectiveness of phage 456 at reducing biofilm formation ([0100]).
Curtin, Gorecka, and Henrotin are silent to “the hydrogel is suspended in a bacteriophage buffer solvent” (instant claim 20) and “wherein the bacteriophage buffer solvent comprises magnesium” (instant claim 21).
Skurnik teaches a composition or matrix comprising a bacteriophage and nanofibrillar cellulose or a derivative thereof in a wet or dry state that is intended to be used in the treatment of a bacterial infection (abstract; [0049], [0113] and [0115]). In an embodiment, the composition or matrix is in a wet state which means the composition or matrix comprises water and/or an aqueous solution, such that nanofibrillar cellulose or the derivative thereof is mixed with water or dispersed in the water or aqueous solution [0043]. The aqueous solution may be an aqueous solution compatible with the bacteriophage, for example a buffer solution (e.g., SM buffer (contains MgSO4) or phage buffer (contains MgCl2)) or saline (e.g., NaCl solution) ([0043]). Skurnik teaches a particular example wherein a bacteriophage in a buffer may be mixed or suspended with a nanofibrillar cellulose hydrogel ([0043]). Skurnik further teaches that Mg2+ ions may be included in the composition or matrix because it may enhance phage stability ([0043]). Skurnik teaches that the composition or matrix may, additionally or alternatively, be a sprayable product, a combination product, an implant, etc. ([0062]). Skurnik also teaches the composition, matrix or arrangement may, additionally or alternatively, be a medical device, a combination product, an implant, etc. ([0094]).
Curtin, Gorecka and Skurnik are drawn to compositions comprising bacteriophages for treating/reducing the risk of infection, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to suspend the hydrogel in a bacteriophage buffer solvent, wherein the bacteriophage buffer solvent comprises magnesium in the invention of Curtin/Gorecka/Henrotin as suggested by Skurnik with a reasonable expectation of success. One of ordinary skill would have been motivated to do so because the prior art teaches that suspending a hydrogel in a bacteriophage buffer solvent comprising magnesium is suitable for applying to a medical device for the purpose of treating or reducing the risk of infection. Additionally, a skilled artisan would have also been motivated to include magnesium because the prior art teaches that the addition of magnesium can enhance phage stability and/or effectiveness.
Thus, the combined teachings of Curtin, Gorecka, Henrotin and Skurnik render the instant claims prima facie obvious.
Response to Arguments
Applicant's arguments, filed 9/25/2025, regarding the 103 rejection over Curtin, Gorecka, Henrotin and Skurnik have been fully considered but they are not persuasive.
Applicant relies on the same arguments as presented for the 103 rejection over Curtin, Gorecka and Henrotin. No further arguments regarding claims 20 and 21 are presented. Remarks, page 13.
For the same reasons as discussed above, Applicant’s arguments are not persuasive.
Thus, said rejection is maintained.
Claims 22, 23 and 25 stand rejected under 35 U.S.C. 103 as being unpatentable over Curtin et al. (US 2009/0191254 A1, Jul. 30, 2009, hereafter as Curtin) in view of Gorecka et al. (WO 2015/063015 A1, May 7, 2015, hereafter as “Gorecka”), Henrotin et al. (US 2012/0315307 A1, Dec. 13, 2012, hereafter as “Henrotin”), and West et al. (WO 2011/009106 A2, Jan. 20, 20011, hereafter as “West”).
The claimed invention is drawn to a medical implant kit, comprising a medical implant (elected species = “orthopedic device”) and a time release anti-bacterial composition applied to at least a portion of at least one surface of the medical implant, wherein the time release anti-bacterial composition comprises: a hydrogel; alginate beads embedded within the hydrogel; and a bacteriophage cocktail encapsulated within the alginate beads, the bacteriophage cocktail comprising: (i) at least one E. coli bacteriophage; and (ii) at least one Klebsiella pneumoniae bacteriophage. Applicant elected “orthopedic device” as the medical implant species.
Regarding instant claims 22 and 23, Curtin teaches medical device coatings comprising one or more bacteriophages and a carrier for the purpose of inhibiting formation of a bacterial biofilm and thereby reducing risk of infection (abstract; [0006]-[0008], [0060]). Curtin teaches the particular bacteriophages that inhibit, Klebsiella pneumoniae and Escherichia coli ([0061]). Curtin also teaches the particular carrier, a hydrogel ([0060]). Curtin further teaches medical devices comprising said coatings and also teaches the particular medical devices, prosthetic joints and orthopedic implants (abstract; [0007] and [0045]) as well as incorporating the bacteriophage compositions into a cement mixture ([0078]).
Curtin is silent to the particular combination of Klebsiella pneumoniae and Escherichia coli (instant claim 22).
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to combine the particular bacteriophages, Klebsiella pneumoniae and Escherichia coli with a reasonable expectation of success because Curtin expressly teaches a finite group of bacteriophages that are suitable as well as combinations of said bacteriophages. Further, "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose” (MPEP 2144.06(I)).
Curtin is silent to bacteriophages encapsulated within alginate beads (instant claim 22).
Gorecka teaches methods of encapsulating a biological material including bacteriophages, a therapeutically active substance, cells, and so on (page 1, lines 4-5; page 6, lines 14-18). In a particular embodiment, Gorecka teaches encapsulating bacteriophages with a polymer, wherein the polymer is alginate, preferably sodium alginate (page 7, lines 11-16). Gorecka teaches that the encapsulated bacteriophages are useful in the treatment of bacterial infection (page 10, lines 2-3). Gorecka also teaches that said encapsulation demonstrates good retention of the encapsulated material (page 5, lines 24-25).
Curtin and Gorecka are drawn to compositions comprising bacteriophages for treating/reducing the risk of infection, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to encapsulate the bacteriophages into alginate beads such as sodium alginate beads into the invention of Curtin as suggested by Gorecka with a reasonable expectation of success. One of ordinary skill would have been motivated to do so because Gorecka teaches that encapsulation of bacteriophages in alginate beads are an effective delivery mode of bacteriophages and said encapsulation demonstrates good retention of the encapsulated material for the purpose of reducing bacterial infection.
Curtin and Gorecka are silent to alginate beads embedded in the hydrogel (instant claim 22).
Henrotin teaches an implantable composition comprising chitosan/alginate beads comprising chondrocytes, said beads embedded in a chitosan hydrogel ([0036]). Henrotin teaches that the biodegradable nature of the implant ensures a progressive resorption after implantation ([0090]).
Curtin and Henrotin are both drawn to compositions comprising hydrogel carriers for biological materials and Gorecka and Henrotin are drawn to encapsulated compositions comprising alginate beads and a biological material encapsulated therein, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to incorporate the alginate beads into the hydrogel as suggested by Henrotin with a reasonable expectation of success. One of ordinary skill would have been motivated to do so because Henrotin teaches encapsulation of biological materials within chitosan/alginate beads embedded in a hydrogel is an effective mode of delivery of biological materials and the combination of degradable beads and degradable hydrogel carrier allows for tunable release of the biological material.
Regarding the limitation, “time release” (instant claim 22), Curtin teaches that the bacteriophage is releasable from a carrier/coating material ([0048] and [0060]) and Gorecka and Henrotin, as discussed above, suggest alginate beads in a hydrogel carrier. Gorecka also teaches a particular embodiment wherein bacteriophages are encapsulated with a polymer, wherein the polymer is alginate (page 7, lines 11-16). Gorecka also teaches that the encapsulated material is releasable (page 8, lines 27-30). Henrotin teaches a biodegradable implantable composition comprising chitosan/alginate beads comprising chondrocytes, said beads embedded in a chitosan hydrogel ([0036] and [0090]).
While the references do not explicitly teach a time release composition, it is noted that the instant specification states, “the alginate beads provide a time release mechanism to the coating, as the beads are stable (i.e., do not melt) at room temperature but will provide gradual release of the bacteriophage as the temperature of the hydrogel increases to body temperature” ([0041]). MPEP 2112.01(I) states,
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product.
In the instant case, Curtin, Gorecka and Henrotin suggest the claimed anti-bacterial coating composition including the alginate beads which are indicated in the instant specification as the structure that provides the function of a time release mechanism. The claimed and prior art products are identical or substantially identical in structure or composition, thus, a prima facie case of obviousness has been established. A skilled artisan would reasonably expect that the identical or substantially identical structure would yield the same characteristics including time release.
Curtin, Gorecka, and Henrotin are silent to a kit (instant claim 22) and at least one of a lubricant and an antiseptic agent (instant claim 25).
West teaches implantable orthopedic compositions and kits thereof (abstract; paragraph bridging pages 16-17; page 42). West teaches that the kit can include any or all components necessary for its intended use (page 43, 3rd full paragraph). For example, the kits may include a number of other suitable articles or components such as artificial joints, tubes sutures, scalpels, needles, syringes, antiseptics for preparation of surgical sites, orthopedic devices, etc. (page 43, 4th full paragraph).
Curtin, Henrotin and Zwirnmann are drawn to orthopedic devices and therapies, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to include a kit comprising any and all components necessary for its intended use such as the implantable device of Curtin/Gorecka/Henrotin and an antiseptic as suggested by West with a reasonable expectation of success. One of ordinary skill would have been motivated to do so because West teaches that it is effective to provide an orthopedic implant and antiseptic in a kit for the intended use of surgical implantation and because it is also conventionally known that kits provide a convenient mechanism to disperse products to consumers.
Thus, the combined teachings of Curtin, Gorecka, Henrotin and West render the instant claims prima facie obvious.
Response to Arguments
Applicant's arguments, filed 9/25/2025, regarding the 103 rejection over Curtin, Gorecka, Henrotin and West have been fully considered but they are not persuasive.
Applicant relies on the same arguments as presented for the 103 rejection over Curtin, Gorecka and Henrotin. No further arguments regarding claims 22, 23 and 25 are presented. Remarks, page 14.
For the same reasons as discussed above, Applicant’s arguments are not persuasive. It is noted that the rejection ahs been modified to reflect that the claim is in independent form and no longer depending from claim 1 which has been cancelled. The grounds of the rejection remain the same.
Thus, said rejection is maintained.
Conclusion
All claims have been rejected; no claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
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