DETAILED ACTION
Response to Arguments
Applicant's arguments filed 17 December 2025 have been fully considered but they are not persuasive.
Rejections under 35 USC § 102: Parris
The remarks take the position on pages 3-4 that Parris fails to disclose the elements of claim 1 because while Parris discusses ion beams have been used to selectively kill tumors in human beams, Parris fails to disclose control microbial organisms or effective dose required to control microorganisms.
This has been found unpersuasive.
Initially, the instant specification expressly recites “It has been discovered that proton beams, when configured to deliver a Bragg Peak dose of radiation to a target region, can effectively control microbial organisms and cure resins” ([0046])
As pointed out by the remarks, Parris teaches curing resins. Parris further teaches irradiating tumors with proton beams ([0030] and [0015]). Therefore, since Parris uses the same proton beam irradiation for curing the resin as for irradiating the tumors, microbial organisms are inherently controlled.
MPEP 2112 (II) recites:
“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention."); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed. Cir. 1999)”
Here, as evidenced by Nejman et al. (Nejman et al. “The human tumor microbiome is composed of tumor type specific intracellular bacteria”) (submitted herewith) “bacteria was first detected in human tumors more than 100 years ago…each tumor type has a distinct microbiome composition. That is, tumors inherently have bacteria (see abstract).
Since the tumor of Parris is irradiated by protons and tumors inherently contain bacteria, bacteria as expressly admitted in the instant specification are controlled. That is, if the proton beam cures resins as disclosed in Parris, it also controls bacteria inherently in the tumors of Parris as admitted in paragraph [0041] of the originally filed specification.
Additionally, as evidenced by Nejman et al. (Nejman et al. “The human tumor microbiome is composed of tumor type specific intracellular bacteria”, Science, 2020) “bacteria was first detected in human tumors more than 100 years ago…each tumor type has a distinct microbiome composition. That is, tumors inherently have bacteria.
Moreover, as evidenced by Park et al. (Park et al., “study of the effects of high-energy proton beams on Escheria coli”, Journal of the Korean physical society, 2015). When irradiating bacteria (e. coli) with proton irradiation at 46 and 93 Gy there is no increase in the populations (see page 5, section III results and discussion, lines 4-11, see also conclusion section on page 8). That is, irradiating bacteria with a proton dose of 46 Gy, is sufficient to control the populations of bacteria.
Lastly, as evidenced by Pusa et al. (US pgPub 2018/0310857) “The total dose required to kill a tumor, which typically is about 20 Gy to 80 Gy, is in general distributed over multiple treatment sessions”
That is, any disclosure of killing a tumor by proton beam irradiation would inherently result in control of microbial organisms. MPEP 2112 (II) recites:
“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention."); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed. Cir. 1999) ”
Here, it was known that the tumors inherently have bacteria (microbial) and dosage required to kill a tumor is within the range of 20 Gy to 80 Gy. Moreover, that bacteria is controlled at proton dose of 46 Gy which is within the range to kill a tumor. Therefore, when applying a 46 Gy dose of protons to kill a tumor, control of bacteria will necessarily result.
Regarding claim 15, the remarks take the position that the toxic product produced from a resin in a tumor discussed in paragraph [0030] of Parris is insufficient to meet the requirement of antibiotic. The remarks suggest a definition of antibiotic and suggest it is incompatible with the toxic agent of Parris. This has been found unpersuasive. Specifically, MPEP 2111.01 (I) recites:
“the plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the relevant time. The ordinary and customary meaning of a term may be evidenced by a variety of sources, including the words of the claims themselves, the specification, drawings, and prior art. However, the best source for determining the meaning of a claim term is the specification - the greatest clarity is obtained when the specification serves as a glossary for the claim terms. Phillips v. AWH Corp., 415 F.3d 1303, 1315, 75 USPQ2d 1321, 1327 (Fed. Cir. 2005) (en banc) ”
Here, the specification provides a better understanding of what is meant by antibiotic in paragraph [0051] which recites:
“certain antibiotic precursor molecules, designed to be inert during administration, can be selectively activated at infection sites through targeted proton beam irradiation. This approach enables localized antibiotic activity while minimizing systemic effects and potential toxicity associated with conventional antibiotic administration”
That is, the instant specification notes that conventional antibiotic administration is toxic and the claimed approach uses localized antibiotic activity while minimizing toxicity. In other words, the antibiotic is understood to be a local toxin selectively activated by a proton beam. Since Parris teaches a local resin in a tumor that is selectively activated by irradiation with protons to release toxins, it is within the broadest reasonable interpretation of the claim. That is, introducing toxins into a tumor is antibiotic because it is toxic to a biological system as suggested in the instant specification.
Therefore the remarks are unpersuasive and the rejection stands as reiterated herein below.
Rejections under 35 USC § 103
The remarks argue this rejection is in error because Parris does not anticipate claim 1. This has been found unpersuasive because Parris does anticipate claim 1 as discussed in detail above.
With respect to claim 11, the remarks take the position that Parris does not teach or suggest any method for in vitro treatment of a sample to control microbial growth.
This has not been found persuasive. Initially, claim 11 only requires the intended use of the method, the only necessitated requirements are a target region is a sample containing microbial organisms within a sealed container. As previously discussed, paragraph [0022] teaches sealing a sample in a container. Parris only fails to disclose the sample containing microbial organisms. However, modifying the method to substitute the resin sample of paragraph [0022] for a microbial sample was found obvious because it would allow for scientists to experiment with different parameters of the proton beam so as to improve the effectiveness of destroying the infection. Further, as desired by paragraph [0019] of Parris.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, 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).
Here, the rational and modification was taken directly from Parris.
The remarks take the position that the rationale suggests in vitro irradiation validly predicts in vivo efficacy without evidence. This was not the rationale for the combination, instead the motivation was to experiment with different parameters to improve the effectiveness of destroying the infection. As evidenced by Park, cited above, this is known to the art. Specifically, Park uses different proton beam doses to determine the effectiveness of destroying bacteria. Therefore, as evidenced by Park, such a modification would have been obvious.
The remarks continue that neither supposed method of in vitro or in vivo microbial are enabling. This has not been found persuasive. As discussed above, the instant specification expressly recites that proton beam irradiation is suitable for both curing a resin and controlling microbial ([0046]). Therefore since Parris teaches curing a resin by proton beam irradiation and treating a tumor (which inherently has bacteria), the same proton is suitable for controlling the microbial of the tumor.
Regarding claim 12, the remarks suggest that Parris fails to disclose irradiation of a medical device package. Paragraph [0030] teaches a resin that releases toxins when irradiated. Therefore the resin may be interpreted to be a medical device package because it contains the toxins to be released to the biological system of the tumor.
With respect to claim 13, the remarks suggest that Parris does not disclose a pharmaceutical composition. This has been found unpersuasive, the toxin is released to the biological system of the tumor, thus a pharmaceutical.
Rejections under § 102(a)(1) Sahadevan
The remarks suggest the sterilized discussed in Sahadevan relates to cells that do not divide anymore. This is immaterial to the claim. The claim requires control of microbial organisms. Sahadevan clearly teaches sterilization of tumors and of parasites (i.e. malaria parasite). Even if there is a difference between sterilization in the context of oncology and microbial organisms, in either case the parasite by irradiation of protons is controlled which is all that is required by claim 1. Therefore the remarks are unpersuasive.
With regards to claim 4, “for treating a localized infection in vivo in a patient” is intended use. The claim has no positive requirements for treating a localized infection inv vivo in a patient, therefore this limitation is not given patentable weight. Specifically, as discussed the target region is an infected tissue region. That is col. 11, lines 59-65 teaches malaria is inactivated at about 1000 Gy and platelets absorb ionizing radiation doses without any cellular damage. Whether this sample is within the patient or without does not change the fact that tissue is infected and if it is inside a patient the same dosage would be required to control malaria.
With regards to claim 5, Sadhanvan teaches a lung which is an organ, thus meets the requirements of the claim.
With regards to claim 6, Sadahavan teaches parasites (i.e. malaria). As discussed above, the intended use is for treating localized infection in vivo. There is no active step of in vivo treatment, therefore the disclosure in col. 11, lines 59-65 would apply whether or not the sample is in the patient or externally therefrom.
Therefore the remarks are unpersuasive the rejections stand as reiterated herein below.
Lastly, it is noted that Park et al. cited above fully anticipates at least claim 1 (see citations above). Moreover, Chawia (USPN 8,357,329) teaches a proton beam to destroy bacteria (see abstract and col. 6, lines 27-41). Wang (US pgPub 2003/0132398) teaches killing bacteria and viruses with proton beams ([0009]). However, because the remarks are not persuasive Park, nor others are not presently applied.
Information Disclosure Statement
Non-patent literature documents have not been considered because they were not submitted in an information disclosure statement (IDS). MPEP 609 recites “"In order to have information considered by the Office during the pendency of a patent application, an information disclosure statement must be (1) in compliance with the content requirements of 37 CFR 1.98, (2) filed in accordance with the procedural requirements of 37 CFR 1.97 and (3) signed in compliance with 37 CFR 1.33(b) (e.g., a separate signed page which references and accompanies the IDS)."
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 1-7, 10 and 14-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Parris (US pgPub 2021/0170639).
Regarding claim 1, Parris teaches a method for controlling microbial organisms ([0015] teaches selectively kill tumors, thus controlling microbial organisms, see also paragraph [0019] for extending proton therapy to treatment of infections), the method comprising:
irradiating a target region containing microbial organisms (proton therapy for tumor or localized infections, see paragraphs [0015]/[0019], thus irradiating a target containing microbial organisms) with a proton beam from an external source (inherent to proton beam therapy), wherein the proton beam is configured and directed to deliver a Bragg Peak dose of radiation selectively to the target region ([0016] note bragg peak scanning applied to tumors or infections see paragraphs [0015]/[0018] or [0019]), and
wherein the Bragg Peak dose is effective to control the microbial organisms (kill tumor or treat localized infection as discussed above).
Regarding claim 2, Parris teaches wherein the step of controlling microbial organisms comprises inhibiting growth of the microbial organisms (kill tumors, see paragraph [0015] or localized infection such as tuberculosis [0019]).
Regarding 3, Parris teaches wherein the step of controlling microbial organisms comprises eliminating the microbial organisms (kill tumors see paragraph [0015] or treat localized infections ([0019])).
Regarding 4, Parris teaches wherein the method is for treating a localized infection in vivo in a patient, and wherein the target region is an infected tissue region ([0005] teaches the particle beam is used to create a 3D pattern of reacting pixels within tumor surrounded by healthy tissue, thus in vivo in the patient having a tumor or localized infection see discussion in paragraphs [0015] and [0019]. Note heal bone in paragraph [0029]).
Regarding 5, Parris teaches infected tissue region is selected from the group consisting of bone, cyst, abscess, tuberculoma, organ, cavity, and sinus (lungs (i.e. cavity), see paragraph [0019] or bone/cavity see paragraph [0029]).
Regarding 6, Parris teaches wherein the microbial organisms are selected from the group consisting of bacteria, fungi, viruses, and parasites (tuberculosis, see paragraph [0019]).
Regarding 7, Parris teaches wherein the microbial organisms are antibiotic-resistant microorganisms ([0009] and [0019], wherein tuberculosis is antibiotic resistant).
Regarding claim 10, Parris teaches wherein the localized infection is selected from the group consisting of tuberculoma, abscess, cyst, sinus infection, gangrene, and intracellular viral infection ([0009]).
Regarding claim 14, Parris teaches 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 ([0030] release of toxic products from resin when irradiated by ion beam (i.e. bioactive therapeutic precursor molecule converted to active therapeutic agent by irradiation)).
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)
Claims 1-8 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 controlling microbial organisms col. 27, lines 25-27 teach the tumor is sterilized by high dose, interlaced microbeam or nanobeam—sterilizing is the process of controlling microbial), the method comprising:
irradiating a target region containing microbial organisms (col. 56, lines 62-67 teach proton microbeams travel towards an isocentric tumor in the patient) 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 target 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 control the microbial organisms (sterilize the tumor thus control microbial organisms).
Regarding claim 2, Sahadeven teaches wherein the step of controlling microbial organisms comprises inhibiting growth of the microbial organisms (sterilization of tumor, see citation above for example from malaria parasite (col. 11, lines 59-65)).
Regarding claim 3, Sahadeven teaches wherein the step of controlling microbial organisms comprises eliminating the microbial organisms (col. 27, lines 25-27, note: sterilization, wherein sterilization is an elimination of microbial organisms).
Regarding claim 4, Sahadeven teaches wherein the method is for treating a localized infection in vivo in a patient, and wherein the target region is an infected tissue region (malaria (col. 11, lines 59-65)).
Regarding claim 5, Sahadeven teaches wherein the infected tissue region is selected from the group consisting of bone, cyst, abscess, tuberculoma, organ, cavity, and sinus (lung see col. 4, lines 1-4).
Regarding claim 6, 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 7, 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 8, 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 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.
Claim(s) 9 and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Parris.
Regarding claim 9, while Parris fails to specifically suggest the localized infection is osteomyelitis in the bone.
However, Parris teaches treating localized infections ([0019]) and healing bones ([0029]). Therefore, it would have been obvious to one of ordinary skill in the art to treat osteomyelitis in the bone with the method of Parris because it would extend the proton therapy to treat localized infections such as osteomyelitis such that the cost of proton therapy is reduced by making it more available to patients that need it ([0019]).
Regarding claim 11, Parris teaches wherein the method is for inhibiting microbial growth in vitro ([0019] teaches proton inhibit infectious diseases and figures 1-2 show a resin irradiated with a proton beam), and wherein the target region is a sample within a sealed container (resin 1, wherein paragraph [0022] teaches the resin may be placed in a sealed reaction vessel).
Parris fails to specifically suggest the sample containing microbial organisms. However, paragraph [0019] suggests treating infections with the proton beam, therefore, it would have been obvious to place a microbial sample in the sealed container of paragraph [0019] because it would allow for scientists to experiment with different parameters of the proton beam so as to improve the effectiveness of destroying the infection.
Regarding claim 12, Parris teaches wherein the sealed container is a medical device package (a reaction vessel [0022] is a medical package device because it packages the resin, which may be implanted into a tumor [0030]).
Regarding claim 13, Parris teaches wherein the sample comprises a pharmaceutical composition ([0030] teaches the resin may have toxins targeted for tumor, thus a pharmaceutical composition).
Conclusion
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.
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