DETAILED ACTION
Response to Arguments
Applicant's arguments filed 30 July 2026 have been fully considered but they are not persuasive.
Claim rejections under 35 USC 112(a):
The remarks take the position that by amendment the claims closely track the instant specification and therefore overcome the lack of written description requirement under 35 USC § 112(a).
The remarks point to possession of the claimed invention by the disclosure of bacteria, fungi, viruses and parasites as contemplated and therefore does not require proof that every species within a genus responds identically to a particular treatment dose.
This has not been found persuasive. Specifically, the instant specification is silent with respect to any type of bacteria, fungi, viruses and parasites receiving a Bragg Peak dose effective to inhibit growth of or eliminate the microbial organisms. MPEP 2163 (II)A3ii recites
“A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)”
Here, there is sufficient variation not only to bacteria, fungi, viruses and parasites, but also a signification variation to each individual species of bacteria, each individual species of fungi, each individual species of viruses and each individual species of parasites.
However, instead of teaching any specific species (for instance malaria (as in Sahadevan) or E. coli was as in Park) the instant specification teaches the claimed a specific dose of 1 to 60 gray is therapeutically effective for inhibiting growth or killing the microorganism ([0013]). However, as evidenced by Sahadevan such a range would not be effective for controlling malaria.
The remarks contend that paragraph [0059] teaches malaria. This has not been found persuasive.
Paragraph [0059] merely teaches malaria like viral pathogens increases cellular susceptibility to radiation induced damage. This paragraph is subsequent paragraph [0056] which merely suggests the present invention demonstrates particular applicability to the following pathological conditions.
Clearly, this does not specifically suggest “wherein the Bragg peak dose is effective to inhibit growth of or eliminate the microbial organism” because this would cover all existing infections (known and unknown), when the specification is silent with respect to a representative number of organisms or infections that could be treated wherein the variations within microorganisms is so great that the disclosed 1-60 greys would clearly be insufficient to treat for instance malaria.
MPEP 2163 further recites:
“Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) ”
Here, paragraph [003] of the instant specification recites:
“Outside of cancer therapy, the potential of proton beams has not been extensively investigated. Conventional approaches to treating microbial infections rely heavily on antibiotic agents. However, the increasing prevalence of antibiotic-resistant microorganisms poses a significant challenge to effective infection management.”
That is, the instant specification admits that outside of cancer therapy the potential of proton beams has not been extensively investigated. Therefore as evident from the specification the use of proton beams outside of cancer therapy (i.e. the claimed Bragg peak dose is effective to inhibit growth of or eliminate the microbial organism) and therefore inhibiting growth or eliminating the microbial organism is not predictable.
Therefore broadly claiming inhibiting growth or eliminating the microbial organisms cannot be satisfied for every known and unknown microbial organism, when no species is disclosed except for the expansive diverse genus of bacteria, bacteria, fungi, viruses, and parasites.
In otherwords, one of ordinary skill in the art as admitted by the specification would look towards antibiotics to treat microbial infections. The use of proton beams for such purposes “has not been extensively studied”. Therefore, because the art is unpredictable and the claim embraces widely variant species, the written description requirement cannot be met because the disclosure does not adequately reflect the structural diversity of the claimed genus by establishment of sufficient species or a reasonable structural function correlation.
Therefore, the remarks are unpersuasive and the rejection stands as reiterated herein below.
With respect to claims 4 and 8, as evident Osborn (“What is osteomyelitis”, MYACARE, 2023) (copy of publication submitted herewith) “Osteomyelitis by definition is an infection and inflammation that takes place in the bone tissue and bone marrow”, wherein S. aureus, Pseudomonas aeruginosa and Serratia marcescens are common bacteria causing osteomyelitis, however Osborn notes “other pathogens can on occasion cause bone infections.”
That is, even the clarification of osteomyelitis is not sufficient representative number of species as in and of itself osteomyelitis is a genus, where no specific species are disclosed. The same could be said for the other options in the group of claim 4.
Claim 6 merely requires that the microbial organisms are antibiotic-resistant microorganisms. There is no disclosure of a representative number of species to reflect the large variations with the genus of antibiotic resistant microorganisms as discussed above in claim 1.
Claim 7 is not sufficient disclosure as discussed above, specifically, such a range is not sufficient to inhibit growth or killing of all microorganism. For instance, malaria could not be treated as evidenced by Sadehaven discussed below.
The remarks with respect to claims 9-10 are unpersuasive for the same reasons above.
Claim 11 has been amended into independent form. The same limitations of the body of claim 1 are reiterated and have the same issues as discussed above.
With respect to claims 14-15 the remarks point to the same language in the specification as claimed. There is no disclosure as to what the claimed bioactive therapeutic precursor molecule is. Indeed, as discussed above, paragraph [003] teaches the applications of proton beam irradiation outside of cancer has not been extensively studied. Therefore, there are no representative species as to what the molecule is and given that this irradiating a molecule with a proton beam outside of cancer treatment is unpredictable, the claims do not meet the written description requirement as to any reaction or bioactive therapeutic precursor molecule. Additionally as previously noted: MPEP 2163.03 (V) recites “An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved”. Here, the claim requires some precursor molecule to be converted to a therapeutic agent (claim 14), specifically an antibiotic (claim 15), however fails to disclose any composition of an agent that converts to an antibiotic upon proton beam irradiation.
Since the specification is devoid of the agent that converts to an antibiotic upon proton irradiation, this amounts to a desired result with no disclosure as to how the result is achieved. That is, by what composition of an agent is it possible to generate an antibiotic.
Rejections under 35 USC § 102 Park:
Park fails to disclose irradiating an infected tissue region, therefore the amendment to claim 1 has overcome Park.
However, with respect to claim 11, the remarks take the position that Park does not disclose selective delivery of a Bragg Peak Dose to an infected tissue region. This has not been found persuasive. Claim 11 requires “the proton beam is configured and directed to deliver a Bragg peak dose of radiation selectively to the sample”. There is no requirement as to how the Bragg peak dose of radiation is delivered selectively. Therefore, the mere act of turning on and of the proton beam is a selective delivery. The claim does not preclude the use of a SOBP and selective is not sufficient to distinguish a SOBP because Park teaches doses 46 and 96 Gy, which is in and of itself a selective delivery of a Bragg peak because it deliveries a particular dose to the sample.
Rejections under 35 USC § 102 Sahadevan
The remarks take the position that Sahadevan fails to disclose “treating a localized infection”.
This has been found unpersuasive. Specifically, claim 1 recites “a method for treating a localized infection in vivo in a patient”. This is an intended use limitation. MPEP 2111.02 (II) recites “if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction”
Here, there is no requirement in the body of the claim to suggest localized infection treatment. Moreover, Sahadevan teaches “High dose and dose rate microbeam and nanobeam radiation at doses in the range of 100 to 1,000 and 4,000 Gy in seconds to milliseconds to a tumor is capable of curing tumors like that of glioblastoma (14). Such high dose radiation in split seconds without much damage to normal tissue was not possible before. The normal tissue toxicity from radiation is minimized or eliminated by peak and valley dose difference and regeneration of the tissue in the peak dose region by migration of cells from the valley region.” (col. 9, lines 30-39).
That is, Sahadevan suggested a localized treatment (without much damage to normal tissue suggests localization) of infection (col. 11, lines 62-67 which teaches applying 1000 gray to inactivate malaria in red cells).
Therefore the remarks are unpersuasive. Specifically, an infected tissue treated with 1000 Gy will sterilize malaria cells (i.e. inactivate malaria).
The dependent claims have been amended and the amendments are addressed herein below.
Lastly, claims 14-15 were not rejected based on Sahadevan, therefore the remarks to this point is moot.
Rejections under 35 USC § 103
In response 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 remarks initially argue that Parris is directed towards a different method than the intended use of localized treatment to of microbial infections. Parris is not relied upon for this intended use. Moreover, Nejman was merely used as evidence that all tumors have a microbiome, therefore, the discussion of irradiating a tumor is irradiating an infected tissue region (i.e. infected with the microbiome). Nejum was not used to teach the various limitations on page 32 of the remarks. Lastly, the remarks at page 33 ignore the fact that Park was additionally used to modify Parris.
The remarks are therefore unpersuasive and the rejection stands, wherein the amended subject matter is specifically addressed herein below.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning (see supplemental remarks filed 31 July 2026), it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Since only knowledge available in the prior art was used, the reconstruction is proper.
Information Disclosure Statement
The information disclosure statement filed 04/24/2026 fails to comply with 37 CFR 1.97(d) because it lacks a timing statement as specified in 37 CFR 1.97(e). It has been placed in the application file, but the information referred to therein has not been considered.
The information disclosure statement filed 04/24/2026 fails to comply with 37 CFR 1.97(d) because it lacks the timing fee set forth in 37 CFR 1.17(p). It has been placed in the application file, but the information referred to therein has not been considered.
Claim Objections
Claim 1 is objected to because of the following informalities: line 3recites “irradiating an infected tissue region region”. Region appears to be duplicated and the duplication must be cancelled. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 4-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 lacks written description for requiring “A method for treating a localized infection in vivo in a patient, the method comprising: irradiating an infected target tissue region region containing microbial organisms with a proton beam from an external source, wherein the proton beam is configured and directed to deliver a Bragg Peak dose of radiation selectively to the infected tissue region, and wherein the Bragg Peak dose is effective to inhibit growth of or eliminate the microbial organisms.”
Specifically, the claim lacks written description for inhibiting growth or eliminating microbial organisms with a Bragg Peak. The broadest reasonable interpretation of the claim is any microbial organism may be controlled an effective dose of Bragg peak. However, the specification does not provide any evidence that all microbial organisms may be controlled by an effective dose of Bragg peak. Paragraph [0013] of the instant published specification teaches that a dose of 1 to 60 gray is therapeutically effective for inhibiting growth or killing the microorganism. However, it is known to Sahadevan (USPN 10,413,755) “malaria sporozoites are inactivated only at about 1000 Gy….It is closer to the 1,000 Gy radiation required to inactivate the malaria sporozoites in red cells (see col. 11, lines 61-67). That is, the instant claim covers any microbial organism (including parasites (see paragraph [0011] of the published specification)), however as evidenced by Sahadevan a dose of 1-60 gray is not effective to control malaria. Therefore, the claim covers specific species with no evidence that the broader genus (including malaria) was envisioned. MPEP 2163.03 (V) recites:
“An original claim may lack written description support when …a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. ”
Here, the claim broadly suggests that any microbial organism may be controlled by an effective a Bragg peak effective dose. However, the specification teaches that by effective dose it is intended to mean 1-60 Gy. Since, as evidenced by Sahadevan, such a dose would be ineffective to control at least malaria, there is no evidence to suggest the applicant had possession of the entire genus of any microbial organism.
Additionally, MPEP 2163 further recites:
“Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) ”
Here, paragraph [003] of the instant specification recites:
“Outside of cancer therapy, the potential of proton beams has not been extensively investigated. Conventional approaches to treating microbial infections rely heavily on antibiotic agents. However, the increasing prevalence of antibiotic-resistant microorganisms poses a significant challenge to effective infection management.”
That is, the instant specification admits that outside of cancer therapy the potential of proton beams has not been extensively investigated. Therefore as evident from the applicant’s specification the use of proton beams outside of cancer therapy (i.e. the claimed Bragg peak dose is effective to inhibit growth of or eliminate the microbial organism) and therefore inhibiting growth or eliminating the microbial organism is not predictable.
Therefore broadly claiming inhibiting growth or eliminating the microbial organisms cannot be satisfied for every known and unknown microbial organism, when no species is disclosed except for the expansive bacteria, bacteria, fungi, viruses, and parasites.
In otherwords, one of ordinary skill in the art as admitted by the specification would look towards antibiotics to treat microbial infections. The use of proton beams for such purposes “has not been extensively studied”. Therefore, because the art is unpredictable and the claim embraces widely variant species, the written description requirement cannot be met because the disclosure does not adequately reflect the structural diversity of the claimed genus by establishment of sufficient species or a reasonable structural function correlation.
Therefore claim 1 fails to meet the written description requirement.
Claims 2-10 and 14-15 fail to meet the written description requirement by virtue of their dependencies on rejected claim 1.
Claim 11 fails to meet the written description requirement as discussed above because it requires commensurate limitations.
Similarly, claim 7 lacks written description for requiring a total dose of 45 Gray to 70 gray. As evidenced by Sahadevan discussed above such a dosage would be insufficient to inhibit growth or kill malaria which is within the broadest reasonably interpretation of claim 8.
Claims 14-15 additionally fail to meet the written description requirement for requiring “activating a chemical reaction in vivo wherein a bioactive therapeutic precursor molecule is converted to an active therapeutic agent by irradiation with the proton beam”. Specifically, the specification is devoid of any specific bioactive therapeutic precursor converted to an active therapeutic agent by proton beam irradiation. MPEP 2163.03 (V) recites “An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved”. Here, the claim requires some precursor molecule to be converted to a therapeutic agent (claim 14), specifically an antibiotic (claim 15), however fails to disclose any composition of an agent that converts to an antibiotic upon proton beam irradiation.
Since the specification is devoid of the agent that converts to an antibiotic upon proton irradiation, this amounts to a desired result with no disclosure as to how the result is achieved. That is, by what composition of an agent is it possible to generate an antibiotic.
For the purposes of examination, it will be interpreted that any conversion from one material to another by proton beam irradiation is sufficient to meet the claim limitation.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 4-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sahadevan (USPN 10,413,755).
Regarding claim 1, Sahadeven teaches a method for treating a localized infection in vivo in a patient (col. 27, lines 25-27 teach the tumor is sterilized by high dose, interlaced microbeam or nanobeam—sterilizing is the process of controlling microbial—for instance radioresistant malaria sporozoites (col. 11, line 45 and col. 11, lines 59-67). Taken together this suggests by sterilization Sahadeven means treating microbial organisms (such as malaria)), the method comprising:
irradiating an infected tissue region region containing microbial organisms (col. 56, lines 62-67 teach proton microbeams travel towards an isocentric tumor in the patient. Tumors inherently have microbial organisms) with a proton beam from an external source (external source seen in figure 10 upstream nozzle 220), wherein the proton beam is configured and directed to deliver a Bragg Peak dose of radiation selectively to the infected tissue region (col. 56, lines 62-67, via collimator the proton beam’s Bragg peak travels towards the tumor in the patient, thus selective targeting via the collimator), and
wherein the Bragg Peak dose is effective to inhibit growth of or eliminate the microbial organisms while minimizing damage to healthy tissue surrounding the infected tissue region (sterilize the tumor thus control microbial organisms—see also col. 11, lines 62-67 which teaches applying 1000 gray to inactivate malaria in red cells. Minimizing damage to healthy tissue is taught on col. 9, lines 30-39).
Regarding claim 4, Sahadeven teaches wherein the localized infection is selected from the group consisting of osteomyelitis, tuberculoma, abscess, sinus infection, gangrene and intracellular viral infection (MPEP 2111.02 (II) recites “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction”. Here, the preamble (claim 1) does not limit the claim because it does not define any of the claimed invention’s limitations and thus has no significance on claim construction. However, platelets infected with malaria (col. 11, lines 59-65). As evidenced by Cleveland Clinic (Cleveland clinic, “Platelets”, 2026), Platelets are located in bone marrow blood and spleen (see page 2)).
Regarding claim 5, Sahadeven teaches wherein the microbial organisms are selected from the group consisting of bacteria, fungi, viruses and parasites (malaria, see col. 11, lines 59-65).
Regarding claim 6, Sahadeven teaches wherein the microbial organisms are antibiotic-resistant microorganisms (malaria is multidrug resistant (col. 8, lines 6-13), since malaria is not bacterial, it is antibiotic resistant).
Regarding claim 7, Sahadeven teaches wherein the Bragg Peak dose of radiation is in a total dose range from 45 Gray to 70 Gray, therapeutically effective for inhibiting growth or killing of the microorganisms in vivo while minimizing damage to healthy tissue surrounding the infected tissue region, and wherein the dose is delivered in fractions 1 Gray to 2 Gray per day (col. 13, lines 63-66 teach 60-80Gy total dose with 1.8 to 2 Gy daily, since the dosages are within the same ranges, the result is inherent).
Claim 8 further limits the localized infection is osteomyelitis (this again does not further limit the claim because the localized infection is intended use in the preamble of claim 1. The body of the claim does require an infected tissue, Sahadeven teaches platelets, which as evidenced by Cleveland clinic is located in bone marrow blood.
Claim Rejections - 35 USC § 103
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.
Claims 1, 4-5 and 9-15 are rejected under 35 U.S.C. 103 as being unpatentable over Parris (US pgPub 2021/0170639) as evidenced by Nejman et al. (Nejman et al. “The human tumor microbiome is composed of tumor type specific intracellular bacteria”) (submitted with the office action of 29 December 2025) in view of Park.
Alternatively, claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Parris (US pgPub 2021/0170639) as evidenced by Nejman et al. (Nejman et al. “The human tumor microbiome is composed of tumor type specific intracellular bacteria”) (submitted with the office action of 29 December 2025) in view of Chawia (USPN 8,357,329) as evidenced by Efthimion et al. (US pgPub 2018/0126189).
Regarding claim 1, Parris teaches a method ([0030]) treating a localized infection in vivo in a patient (intended use), the method comprising:
irradiating an infected tissue region containing microbial organisms ([0030] teaches introducing a small piece of resin into a tumor and targeting the resin with an ion beam (thus irradiating a portion of the tumor). As evidenced by the abstract of Nejman tumors inherently have a microbiome, thus infected) with a proton beam from an external source ([0030] teaches ion beam, abstract teaches that by ion beam Parris means proton beams, figure 1 is evidence that the proton beam is external), wherein the proton beam is configured and directed to deliver a Bragg Peak dose of radiation selectively to the infected tissue region ([0030] teaches targeting the resin with a ion beam (i.e. proton), abstract teaches Bragg peak of the ion beam controls polymerization. Note as discussed above, Nejman is evidence that tumors have microbiome, thus infected tissue. Since the ion beam targets the resin it selectively delivers the Bragg peak to the tumor (i.e. targeting the resin)), while minimizing damage to healthy tissue surrounding the infected tissue region (since the ion beam targets the resin in the tumor ([0030]) damage to healthy tissue surrounding the resin and not irradiated is minimized).
Parris suggests extending proton therapy to treatment of localized infections, however fails to expressly disclose wherein the Bragg Peak dose is effective to control the microbial organisms.
However, Park teaches a proton dose of 46 Gy no increase of populations of e. coli until 1 hour and 40 min (page 5, section 3). Note instant specification teaches this is an effective dose to control microbials (see paragraph [0013] of the published application)
Park modifies Parris by suggesting an effective dose for the Bragg peak of Parris.
Since both inventions are directed towards directing proton beams towards tumors, it would have been obvious to one of ordinary skill in the art to apply the dosage of Park to the Bragg peak of Parris because it would facilitate the treatment of antibiotic resistant infection when treating a tumor that is infected.
Alternatively, Chawia teaches wherein the Bragg Peak dose is effective to control the microbial organisms (col. 6, lines 15-22 teaches eradicating deadly pathogenic bacterium with protons and col. 6, lines 30-32 teaches focusing protons on an infected area. As evidenced by Efthimion et al. “All protons of a given energy have a certain range, defined by the Bragg peak” ([0006]). Since Chawia teaches protons there is inherently has a Bragg peak over a certain range).
Chawia modifies Parris by suggesting destroying bacterium with protons.
Since both inventions are directed towards irradiating a target with a proton beam, it would have been obvious to one of ordinary skill in the art to irradiate the target of Parris with a proton beam sufficient to eradicate bacteria because it would help to destroy infection while releasing toxic material thus treating both the tumor and infection with a single treatment.
Regarding claims 4 and 9, Parris teaches wherein the localized infection is selected from a group consisting of osteomyelitis, tuberculoma, abcess, sinus infection, gangrene and intracellular viral infection (MPEP 2111 (II). Note the claimed localized infection is an intended use of claim 1, therefore limiting the intended use adds nothing more to claim construction. Claim 1 does require “an infected tissues”, however there is no nexus between the localized infection and the claimed infected tissue).
Regarding claim 5, Parris in view of Park teaches wherein the microbial organism is selected from bacteria (Parris as evidenced by Nejman teaches that all tumors have a microbiome, thus inherently infected. Alternatively Park, e. coli see abstract).
Regarding claim 10, Parris teaches wherein the localized infection is comprises an intercellular viral infection (MPEP 2111 (II). Note the claimed localized infection is an intended use of claim 1, therefore limiting the intended use adds nothing more to claim construction. Claim 1 does require “an infected tissues”, however there is no nexus between the localized infection and the claimed infected tissue).
Regarding claim 11, Parris fails to disclose wherein the method is for inhibiting microbial growth in vitro, and wherein the target region is a sample containing microbial organisms within a container.
However, Park teaches wherein the method is for inhibiting microbial growth in vitro, and wherein the target region is a sample containing microbial organisms within a container (page 4 under proton beam irradiation section, note: “Eppendorf tubes containing E. coli culture medium…were irradiated” thus in vitro within a container (i.e. tube)).
Park modifies Parris by suggesting containing a sample within Eppendorf tubes.
Since both inventions are directed towards irradiation of a sample with proton beams, it would have been obvious to one of ordinary skill in the art to perform the irradiation on a sample within a container to study and optimize parameters of the proton beam prior to patient treatment to ensure safety and efficacy.
The combined method fails to suggest a sealed container, however it would have been obvious to seal the Eppendorf tubes of Parris in view of Park in order to prevent contamination of the sample or any accidental spill.
Regarding claim 12, Parris in view of Park teaches wherein the sealed container is a medical device package (Park Eppendorf tubes is a medical device package. Note it would be obvious to seal the Eppendorf tubes as discussed above).
Regarding claim 13, Parris teaches the sample comprises a pharmaceutical composition ([0030], HCl).
Regarding claim 14, Parris teaches activating a chemical reaction in vivo ([0030] via proton irradiation of resin) wherein a bioactive therapeutic precursor molecule ([0030] resin) is converted to an active therapeutic agent by irradiation with the proton beam (protons cause breakdown and release of compounds (e.g. HCl). HCl is interpreted as a therapeutic agent).
Regarding claim 15, where the bioactive therapeutic precursor molecule is converted to an antibiotic agent upon irradiation with the proton beam ([0030] note toxic, thus antibiotic).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Sahadeven as evidenced by Cleveland (Cleveland clinic, “Platelets”, 2026) (submitted herewith)
Regarding claim 9, Sahadeven teaches wherein the localized infection is osteomyelitis (dependent upon claim 4, where the localized infection is required as intended use, therefore does not limit the claim see discussion above in claim 4).
While Sahadevan teaches red cells of platelets with malaria, Sahadevan fails to disclose the infected tissue region is bone tissue.
However, Cleveland is evidence that platelets are located in the blood, spleen and bone marrow (see page 2).
Therefore, it would have been obvious to one of ordinary skill in the art that the malaria infected platelets of Sahadevan are located in bone marrow of the bone because it is one of the three locations of platelets as evidenced by Cleveland.
Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Park (submitted with the office action of 29 December 2025)
Regarding claim 11, Park teaches a method for inhibiting microbial growth in vitro (see page 5, section III results and discussion, lines 4-11, see also conclusion section on page 8), the method comprising:
irradiating a sample containing microbial organisms within a container with a proton beam from an external source(page 5, section III, results and discussion, proton irradiation of bacteria solution. Also page 4, “proton beam irradiation” note Eppendorf tubes contain the E. coli culture, thus a container irradiated with a proton beam),
wherein the proton beam is configured and directed to deliver a Bragg Peak dose of radiation selectively to the sample (page 3, last paragraph before section II, recites “E. coli was exposed to spread out Bragg peak protons at doses, note as discussed above “selectively” is interpreted as merely turning on or off the proton beam to deliver the prescribed doses), and wherein the Bragg Peak dose is effective to inhibit growth of or eliminate the microbial organisms (page 5, section III at 46 and 93 Gy there was no increase in populations of bacterial cells, thus control of E coli bacteria.).
Park fails to suggest a sealed container, however it would have been obvious to seal the Eppendorf tubes of Parris in view of Park in order to prevent contamination of the sample or any accidental spill.
Regarding claim 12, Park teaches wherein the sealed container is a medical device package (Park Eppendorf tubes is a medical device package. Note it would be obvious to seal the Eppendorf tubes as discussed above).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL J LOGIE whose telephone number is (571)270-1616. The examiner can normally be reached M-F: 7:00AM-3:00PM.
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/MICHAEL J LOGIE/Primary Examiner, Art Unit 2881
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