DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/16/2026 has been entered.
Response to Amendment
Claims 1, 6, 8, and 12 have been amended. Claims 1-6, 8-16, and 18-20 remain pending.
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.
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 1-5 and 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Mahadevan et al. (Int. J. Radiation Oncology Biol. Phys., Vol. 78, No. 3, pp. 735- 742, 2010, henceforth Mahadevan) in view of Park et al. (Radiation Research, 177(3) : 311-327, henceforth Park), Gerrans et al. (US 20120259215, henceforth Gerrans), and Lewandowski et al. (Lewandowski RJ, Geschwind JF, Liapi E, Salem R. Transcatheter intraarterial therapies: rationale and overview. Radiology. 2011 Jun;259(3):641-57. doi: 10.1148/radiol.11081489. PMID: 21602502; PMCID: PMC3400295, henceforth Lewandowski), as evidenced by Jain (Jain RK. Delivery of molecular and cellular medicine to solid tumors. Adv Drug Deliv Rev. 2012 Dec 1;64(Suppl):353-365. doi: 10.1016/j.addr.2012.09.011. PMID: 24511174; PMCID: PMC3914635, henceforth Jain).
Regarding claim 1, Mahadevan discloses a method of cancer treatment comprising treating a target area including a tumor (radiation was given to tissue including a tumor, see section “SBRT dose prescription” on pg. 376) with radiation in the target area (see section “SBRT dose prescription” on pg. 376) followed by delivering a dose of an agent local to the target area (see section “Systemic chemotherapy” on pg. 376; Mahadevan discloses multiple doses of an agent being delivered, which includes a dose; systemic chemotherapy administration as in Mahadevan includes delivery of the agent to all areas of the body, thus including areas local to the tumor, or local areas).
Mahadevan does not explicitly teach that its radiation is to reduce a microvasculature in the target area; that when the dose is delivered, the target area has a reduced microvasculature; or that the reduced microvasculature is a reduction in connections between the treated area and a venous system. Park teaches that treatment with radiation of tumors can cause a reduced microvasculature (see right column of pg. 312, “The conclusions of other studies on human tumors (19–24) follow a general trend that blood flow remains unchanged or increases slightly during the early period of fractionated radiotherapy but decreases toward the end of treatments”, where the decreasing blood flow is a result of reduction in microvasculature) including deterioration of vasculature of the tumor (lines 3-7 of the right column of pg. 317) wherein the reduced microvasculature is a reduction in connections between the treated segment and a venous system (see lines 3-7 of the right column of pg. 317, “In most cases, after tumors are irradiated with doses higher than 15–20 Gy in a single exposure, tumor blood flow decreases rapidly followed by deterioration of the vasculature as the tumor volume decreases”), as well as that in some instances, decreasing microvasculature as a result of radiation therapy lead to better outcomes (see the last lines of the right column of pg. 312, “Pirhonen et al. (20) reported that a decrease of tumor vasculature during the fractionated radiotherapy of advanced cervical carcinoma was associated with a better treatment outcome”). Park additionally teaches that a variety of treatment protocols could be followed for the administration of radiation therapy to treat cancer (see Table 1, a variety of treatment protocols are provided as possible administration plans for different cancers).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have delivered a dose of radiation therapy which would have reduced microvasculature as claimed as Park teaches this to be better associated with positive treatment outcomes in some instances (see the last lines of the right column of pg. 312, “Pirhonen et al. (20) reported that a decrease of tumor vasculature during the fractionated radiotherapy of advanced cervical carcinoma was associated with a better treatment outcome”). Further, as Park teaches that the dosage of radiation is variable for different cancers (see Table 1) one of ordinary skill in the art would have had a reasonable expectation of success in modifying the radiation to achieve the necessary treatment outcome. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have selected the dosage used for radiation therapy for the provided indication such that microvasculature was reduced as Park teaches this is associated with better treatment outcomes and that dosage of radiation is a result effective variable which can be changed for treatment of different cancers and as such selecting a radiation dosage would have been a matter of optimization since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980).
Mahadevan does not teach isolating a segment of a lumen within or adjacent to the tumor in the target area using a catheter device inserted into the lumen; delivering a dose of an agent local to the target area having a reduced microvasculature from the isolated segment via the catheter device. Gerrans teaches a method comprising: treating a target area (delivery of therapeutic agents at specified locations such as body cavity 60 in fig. 3A, [0003]) including a tumor (tumor 62, fig. 3A); isolating a segment of a lumen (See [0024] – the creating of chamber 64 is considered to be isolating a segment of a lumen which is bodily cavity 60 in fig. 3A) within or adjacent to the tumor in the target area (See tissue of [0032] – this is understood to be the tumor in light of [0014] and [0015]; see also tumor 62 of fig. 3A which is adjacent to chamber 64) using a catheter device (Catheter assembly 21, fig. 1) inserted into the lumen (See fig. 3A and [0063], the assembly is inserted into the bodily cavity which is the lumen); delivering a dose of an agent (See [0071]) local to the target area from the isolated segment (Chamber 64, fig. 3B; this administration is considered to be local because, as shown in fig. 3A, the isolated segment 64 and tumor 62 are immediately adjacent to each other and are thus local to each other) via the catheter device (The structures shown in figs. 3A-D are part of catheter assembly 21 as shown in fig. 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have followed the treatment protocol of Mahadevan and used the device of Gerrans for the dose delivery in the protocol of Mahadevan, as this would yield the benefit of the treatment protocol of Mahadevan, which is achieving the local control benefits of radiotherapy with a shorter duration of treatment to lessen the effect on patient’s lives (see Discussion section on pgs. 739 and 740), and it would yield the benefit of the device of Gerrans, which is a reduced amount of unwanted chemotherapy extravasation causing negative side effects as a result of the localized delivery ([0011]-[0015]).
The modified treatment method of Mahadevan using the device of Gerrans thus discloses the method wherein the target area including the tumor is treated at a first time (this is the first time when SBRT is delivered as in the “Treatment planning” section of pg. 736 of Mahadevan) to reduce the microvasculature (See Park lines 3-7 of the right column of pg. 317, radiation can cause reduction of microvasculature) at time that is between two weeks and six months prior to the isolation of a segment of the lumen (Chemotherapy begins 1 month later, see the “Treatment planning” section of pg. 736).
The modified treatment method of Mahadevan using the device of Gerrans does not disclose that the lumen is an arterial lumen, nor does it disclose delivering the dose of the agent to the target area across a wall of the arterial lumen and into the adventitia and interstitium to reach the tumor. Lewandowski teaches that intraarterial chemoinfusion (or drug delivery of a chemotherapeutic agent from within an arterial lumen) is preferable to systemic chemotherapy infusion as it demonstrates highly effective tumor responses with reduced toxicity profiles (see “Essentials” point 3 in col. 1 of pg. 642 and see col. 1 par. 3 of pg. 645).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have followed the treatment method of Mahadevan using the device of Gerrans through intraarterial chemoinfusion for the benefit of increased drug uptake in tumors and reduced systemic toxicity (Lewandowski pg. 645 col. 1 par. 3). This could be achieved where the bodily cavity of Gerrans is an artery, especially since an artery is a cavity where it is a hollow elongated opening; thus, placing the device of Gerrans in an artery is considered to be the modified method. Additionally, Jain provides evidence that that molecules entered into the blood transport across the vessel wall (see at least Jain pg. 001, col. 2, par. 2, and pgs. 005-006 section “Transport across the microvascular wall”), and thus the intraarterial chemoinfusion would include the agent (which is the chemotherapeutic agent) being delivered across a wall of the arterial lumen and into the adventitia and interstitium (which are the connective tissue structures known to be on the outside of vessel walls) to reach the tumor. Jain further evidences that radiation treatment causes the reduced microvasculature to be configured to increase tissue concentration of a localized delivered dose of the agent via reducing washout of the delivered dose of the agent (see Jain pg. 581, right column, par. 2, “As discussed in the previous section, tumor vessels are highly permeable to macromolecules. If these vessels could be made even more permeable using radiation (delivered by an external source or by heavily labelling macromolecules with radioisotopes), then the localization of macromolecules in tumors could be increased further for detection or treatment” is an evidencing that radiation treatment causes increased local concentration of treatment).
Regarding claim 2, the modified treatment method of Mahadevan using the device of Gerrans discloses the method further comprising inserting the catheter device into the lumen within or adjacent to the tumor (See Gerrans fig. 3A – the catheter assembly 21 is inserted into bodily cavity 60 which is adjacent to tumor 62), the catheter device including a first occluder (Balloon 28, fig. 3A) and a second occluder (Balloon 30, fig. 3A).
Regarding claim 3, the modified treatment method of Mahadevan using the device of Gerrans discloses the method wherein isolating the segment includes expanding the first occluder and the second occluder (See Gerrans [0063] and [0067] – Examiner notes that in [0063], disclosure says “proximal balloon 38 is inflated”, which is understood to mean proximal balloon 28).
Regarding claim 4, the modified treatment method of Mahadevan using the device of Gerrans discloses the method wherein the agent is a chemotherapeutic agent (See Gerrans [0071] and Mahadevan “Systemic chemotherapy” section on pg. 736).
Regarding claim 5, the modified treatment method of Mahadevan using the device of Gerrans discloses the method wherein the chemotherapeutic agent includes one or more compounds selected from a group consisting of: fluorouracil, gemcitabine hydrochloride, doxorubicin, and mitomycin C (all in Gerrans [0071]).
Regarding claim 8, the modified treatment method of Mahadevan using the device of Gerrans discloses the method wherein the microvasculature was treated to reduce the microvasculature in the target area by administration of a dose of radiation (Mahadevan, see section “SBRT dose prescription” on pg. 376).
Regarding claim 9, the modified treatment method of Mahadevan using the device of Gerrans discloses the method wherein treating the target area comprises administering the dose of radiation wherein the dose of radiation includes an amount of radiation totaling between 20 and 50 gray (Treatment options were between 24-36 Gy, see “SBRT dose prescription” section of pg. 736; in the modified method with the optimized dosing of radiation, this range could still be maintained by changing the fractioning of the radiation treatment such as to yield the reduced microvasculature as claimed and providing the optimal treatment protocol).
Regarding claim 10, the modified treatment method of Mahadevan using the device of Gerrans discloses the method wherein the amount of radiation is selected based on one or more characteristics of the tumor, the one or more characteristics of the tumor including at least one of: a location of the tumor (Location of tumor in determines dosage, see “SBRT dose prescription” of pg. 736), and a size of the tumor.
Regarding claim 11, the modified treatment method of Mahadevan using the device of Gerrans discloses the method wherein the agent includes a dye (Gerrans [0076]-[0078]).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Mahadevan et al. (Int. J. Radiation Oncology Biol. Phys., Vol. 78, No. 3, pp. 735- 742, 2010, henceforth Mahadevan) in view of Park et al. (Radiation Research, 177(3) : 311-327, henceforth Park), Gerrans et al. (US 20120259215, henceforth Gerrans) and Lewandowski et al. (Lewandowski RJ, Geschwind JF, Liapi E, Salem R. Transcatheter intraarterial therapies: rationale and overview. Radiology. 2011 Jun;259(3):641-57. doi: 10.1148/radiol.11081489. PMID: 21602502; PMCID: PMC3400295, henceforth Lewandowski), as evidenced by Jain (Jain RK. Delivery of molecular and cellular medicine to solid tumors. Adv Drug Deliv Rev. 2012 Dec 1;64(Suppl):353-365. doi: 10.1016/j.addr.2012.09.011. PMID: 24511174; PMCID: PMC3914635, henceforth Jain) as applied to claim 1 above, and further in view of Multhoff et al. (Frontiers in Oncology, 2012; 2(165); pp. 1-6, November 2012, henceforth Multhoff) and Degani et al. (US 20090264734, henceforth Degani).
Regarding claim 6, the modified treatment method of Mahadevan using the device of Gerrans discloses the method wherein delivering the dose comprises adjusting an intraluminal pressure of the segment (See Gerrans [0025] wherein it teaches repeating an increasing and decreasing of fluid pressures within the isolated segment) and delivering the dose of the agent to the segment via the catheter device (Gerrans [0067]).
The treatment method of Mahadevan using the device of Gerrans does not disclose reducing an intraluminal pressure of the segment to a level of pressure of an interstitial space between the lumen and the target area wherein the level of pressure includes 10-20 mmHg. Multhoff teaches that it is beneficial for drug extravasation for the pressure of the blood vessel from which chemotherapy is administered to be at least the same as or higher than the pressure of the interstitial fluid pressure of the tumor (pg. 4 paragraphs 2 and 5). Degani teaches that an interstitial fluid pressure of a tumor can be 10-50 mmHg ([0030]).
Since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art (In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980)), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have adjusted the fluid pressures within the isolated segment as claimed in the modified method of Mahadevan as Gerrans teaches adjusting the fluid pressure within the isolated segment to achieve desired treatment, and further to have reduced the fluid pressure to the claimed value as Multhoff teaches having the minimum pressure be equal to the interstitial fluid pressure of the tumor (or the space between the lumen and the target area) to prevent inadequate delivery of anticancer agents such as chemotherapy molecules because of improperly balanced pressure gradients (pg. 4 paragraph 5) and Degani teaches such values to be known for the interstitial fluid pressure of a tumor.
Claims 12-16 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Mahadevan et al. (Int. J. Radiation Oncology Biol. Phys., Vol. 78, No. 3, pp. 735- 742, 2010, henceforth Mahadevan) in view of Park et al. (Radiation Research, 177(3) : 311-327, henceforth Park), Gerrans et al. (US 20120259215, henceforth Gerrans), Multhoff et al. (Frontiers in Oncology, 2012; 2(165); pp. 1-6, November 2012, henceforth Multhoff), Degani et al. (US 20090264734, henceforth Degani), and Lewandowski et al. (Lewandowski RJ, Geschwind JF, Liapi E, Salem R. Transcatheter intraarterial therapies: rationale and overview. Radiology. 2011 Jun;259(3):641-57. doi: 10.1148/radiol.11081489. PMID: 21602502; PMCID: PMC3400295, henceforth Lewandowski), as evidenced by Jain (Jain RK. Delivery of molecular and cellular medicine to solid tumors. Adv Drug Deliv Rev. 2012 Dec 1;64(Suppl):353-365. doi: 10.1016/j.addr.2012.09.011. PMID: 24511174; PMCID: PMC3914635, henceforth Jain).
Regarding claim 12, Mahadevan discloses a method of cancer treatment comprising treating a target area including a tumor (radiation was given to tissue including a tumor, see section “SBRT dose prescription” on pg. 376) with radiation in the target area (see section “SBRT dose prescription” on pg. 376) followed by delivering a dose of an agent local to the target area (see section “Systemic chemotherapy” on pg. 376; Mahadevan discloses multiple doses of an agent being delivered, which includes a dose; systemic chemotherapy administration as in Mahadevan includes delivery of the agent to all areas of the body, thus including areas local to the tumor, or local areas).
Mahadevan does not explicitly teach that its radiation is to reduce a microvasculature in the target area; that when the dose is delivered, the target area has a reduced microvasculature; or that the reduced microvasculature is a reduction in connections between the treated area and a venous system. Park teaches that treatment with radiation of tumors can cause a reduced microvasculature (see right column of pg. 312, “The conclusions of other studies on human tumors (19–24) follow a general trend that blood flow remains unchanged or increases slightly during the early period of fractionated radiotherapy but decreases toward the end of treatments”, where the decreasing blood flow is a result of reduction in microvasculature) including deterioration of vasculature of the tumor (lines 3-7 of the right column of pg. 317) wherein the reduced microvasculature is a reduction in connections between the treated segment and a venous system (see lines 3-7 of the right column of pg. 317, “In most cases, after tumors are irradiated with doses higher than 15–20 Gy in a single exposure, tumor blood flow decreases rapidly followed by deterioration of the vasculature as the tumor volume decreases”), as well as that in some instances, decreasing microvasculature as a result of radiation therapy lead to better outcomes (see the last lines of the right column of pg. 312, “Pirhonen et al. (20) reported that a decrease of tumor vasculature during the fractionated radiotherapy of advanced cervical carcinoma was associated with a better treatment outcome”). Park additionally teaches that a variety of treatment protocols could be followed for the administration of radiation therapy to treat cancer (see Table 1, a variety of treatment protocols are provided as possible administration plans for different cancers).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have delivered a dose of radiation therapy which would have reduced microvasculature as claimed as Park teaches this to be better associated with positive treatment outcomes in some instances (see the last lines of the right column of pg. 312, “Pirhonen et al. (20) reported that a decrease of tumor vasculature during the fractionated radiotherapy of advanced cervical carcinoma was associated with a better treatment outcome”). Further, as Park teaches that the dosage of radiation is variable for different cancers (see Table 1), one of ordinary skill in the art would have had a reasonable expectation of success in modifying the radiation to achieve the necessary treatment outcome. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have selected the dosage used for radiation therapy for the provided indication such that microvasculature was reduced as Park teaches this is associated with better treatment outcomes and that dosage of radiation is a result effective variable which can be changed for treatment of different cancers and as such selecting a radiation dosage would have been a matter of optimization since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980).
Mahadevan does not teach isolating a segment of a lumen within or adjacent to the tumor in the target area using a catheter device inserted into the lumen; delivering a dose of an agent to the target area having a reduced microvasculature from the isolated segment via the catheter device. Gerrans teaches a method comprising: treating a target area (delivery of therapeutic agents at specified locations such as body cavity 60 in fig. 3A, [0003]) including a tumor (Tumor 62 is target site as in [0063] and fig. 3A); isolating a segment of a lumen (See [0024] – the creating of chamber 64 is considered to be isolating a segment of a lumen which is bodily cavity 60 in fig. 3A) closest to the tumor in the target area (See tissue of [0032] – this is understood to be the tumor in light of [0014] and [0015]) using a catheter device (Catheter assembly 21, fig. 1) inserted into the lumen (See fig. 3A and [0063], the assembly is inserted into the bodily cavity which is the lumen); decreasing an intraluminal pressure of the segment (See Gerrans [0025] wherein it teaches repeating an increasing and decreasing of fluid pressures within the isolated segment); and delivering a dose of an agent (See [0071]) to the target area ([0067]) from the isolated segment (Chamber 64, fig. 3B).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have followed the treatment protocol of Mahadevan and used the device of Gerrans for the dose delivery in the protocol of Mahadevan, as this would yield the benefit of the treatment protocol of Mahadevan, which is achieving the local control benefits of radiotherapy with a shorter duration of treatment to lessen the effect on patient’s lives (see Discussion section on pgs. 739 and 740), and it would yield the benefit of the device of Gerrans, which is a reduced amount of unwanted chemotherapy extravasation causing negative side effects as a result of the localized delivery ([0011]-[0015]).
The modified treatment method of Mahadevan using the device of Gerrans thus discloses the method wherein the target area including the tumor is treated at a first time (this is the first time when SBRT is delivered as in the “Treatment planning” section of pg. 736 of Mahadevan) to reduce the microvasculature (See Park lines 3-7 of the right column of pg. 317, radiation can cause reduction of microvasculature) at time that is between two weeks and six months prior to the isolation of a segment of the lumen (Chemotherapy begins 1 month later, see the “Treatment planning” section of pg. 736).
The treatment method of Mahadevan using the device of Gerrans does not disclose decreasing an intraluminal pressure of the segment to a level of pressure of an interstitial space between the lumen and the target area or increasing the intraluminal pressure to greater than a pressure of the interstitial space between the lumen and the target area wherein the level of pressure includes 10-20 mmHg. Multhoff teaches that it is beneficial for drug extravasation for the pressure of the blood vessel from which chemotherapy is administered to be at least the same as or higher than the pressure of the interstitial fluid pressure of the tumor (pg. 4 paragraphs 2 and 5). Degani teaches that an interstitial fluid pressure of a tumor can be 10-50 mmHg ([0030]).
Since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art (In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980)), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have adjusted the fluid pressures within the isolated segment as claimed in the modified method of Mahadevan as Gerrans teaches adjusting the fluid pressure within the isolated segment to achieve desired treatment, and further to have reduced the fluid pressure to the claimed value as Multhoff teaches having the minimum pressure be equal to the interstitial fluid pressure of the tumor (or the space between the lumen and the target area) to prevent inadequate delivery of anticancer agents such as chemotherapy molecules because of improperly balanced pressure gradients (pg. 4 paragraph 5) and Degani teaches such values to be known for the interstitial fluid pressure of a tumor.
The modified treatment method of Mahadevan does not disclose that the lumen is an arterial lumen, nor does it disclose delivering the dose of the agent to the target area across a wall of the arterial lumen and into the adventitia and interstitium to reach the tumor. Lewandowski teaches that intraarterial chemoinfusion (or drug delivery of a chemotherapeutic agent from within an arterial lumen) is preferable to systemic chemotherapy infusion as it demonstrates highly effective tumor responses with reduced toxicity profiles (see “Essentials” point 3 in col. 1 of pg. 642 and see col. 1 par. 3 of pg. 645).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have followed the treatment method of Mahadevan using the device of Gerrans through intraarterial chemoinfusion for the benefit of increased drug uptake in tumors and reduced systemic toxicity (Lewandowski pg. 645 col. 1 par. 3). This could be achieved where the bodily cavity of Gerrans is an artery, especially since an artery is a cavity where it is a hollow elongated opening; thus, placing the device of Gerrans in an artery is considered to be the modified method. Additionally, Jain provides evidence that that molecules entered into the blood transport across the vessel wall (see at least Jain pg. 001, col. 2, par. 2, and pgs. 005-006 section “Transport across the microvascular wall”), and thus the intraarterial chemoinfusion would include the agent (which is the chemotherapeutic agent) being delivered across a wall of the arterial lumen and into the adventitia and interstitium (which are the connective tissue structures known to be on the outside of vessel walls) to reach the tumor. Jain further evidences that radiation treatment causes the reduced microvasculature to be configured to increase tissue concentration of a localized delivered dose of the agent via reducing washout of the delivered dose of the agent (see Jain pg. 581, right column, par. 2, “As discussed in the previous section, tumor vessels are highly permeable to macromolecules. If these vessels could be made even more permeable using radiation (delivered by an external source or by heavily labelling macromolecules with radioisotopes), then the localization of macromolecules in tumors could be increased further for detection or treatment” is an evidencing that radiation treatment causes increased local concentration of treatment).
Regarding claim 13, the modified treatment method of Mahadevan using the device of Gerrans discloses the method wherein the segment of the lumen is isolated using the catheter device (See Gerrans [0063] and [0067] – Examiner notes that in [0063], disclosure says “proximal balloon 38 is inflated”, which is understood to mean proximal balloon 28) by expanding a first occluder (Balloon 28, fig. 3A) and a second occlude (Balloon 30, fig. 3A), wherein distance between the first occluder and the second occluder is adjustable (See [0024] and [0025]).
Regarding claim 14, the modified treatment method of Mahadevan using the device of Gerrans discloses the method further comprising measuring the intraluminal pressure of the segment (See Gerrans, Sensor such as for pressure as in [0069] is used for this) using a pressure sensor (Sensor such as for pressure as in [0069]) in communication with the catheter device (Sensor such as for pressure as in [0069] is connected to a pump 22 which is in communication with assembly 21, fig. 1).
Regarding claim 15, the modified treatment method of Mahadevan using the device of Gerrans discloses the method wherein the target area including the tumor was treated between two weeks and six months prior to reduce a microvasculature in the target area by treatment with a chemotherapeutic agent (See Gerrans [0071] and [0074] and Mahadevan “Systemic chemotherapy” section on pg. 736).
Regarding claim 16, the modified treatment method of Mahadevan using the device of Gerrans discloses the method wherein the chemotherapeutic agent includes one or more compounds selected from a group consisting of: fluorouracil, gemcitabine hydrochloride, doxorubicin, and mitomycin C (all in Gerrans [0071]).
Regarding claim 18, the modified treatment method of Mahadevan using the device of Gerrans discloses the method wherein the target area including the tumor was treated between two weeks and six months prior to reduce a microvasculature in the target area by administration of a dose of radiation (Mahadevan, see section “SBRT dose prescription” on pg. 376).
Regarding claim 19, the modified treatment method of Mahadevan using the device of Gerrans discloses the method wherein treating the target area comprises administering the dose of radiation wherein the dose of radiation includes an amount of radiation totaling between 20 and 50 gray (Treatment options were between 24-36 Gy, see “SBRT dose prescription” section of pg. 736).
Regarding claim 20, the modified treatment method of Mahadevan using the device of Gerrans discloses the method wherein the amount of radiation is selected based on one or more characteristics of the tumor, the one or more characteristics of the tumor including at least one of: a location of the tumor (Location of tumor in determines dosage, see “SBRT dose prescription” of pg. 736), and a size of the tumor.
Response to Arguments
Applicant's arguments filed 04/06/2026 have been fully considered but they are not persuasive.
Applicant first argues that Park does not evidence that Mahadevan discloses the reduced microvasculature as claimed because the required dosing of Park is higher than that relied on in Mahadevan. This is persuasive, however the argument has been rendered moot by the new grounds of rejection.
Applicant also argues that Multhoff points out that coupling interstitial fluid pressure and microvascular pressure can reduce perfusion pressure between blood vessels around a tumor which is taught to be detrimental to delivery. Applicant further argues that Multhoff does not teach how to improve drug delivery by reducing intraluminal pressure as claimed. Examiner respectfully disagrees; a teaching that coupling between interstitial fluid pressure and microvascular pressure causes a reduction in detrimental perfusion is considered to be a teaching that such a coupling is an improvement, as a reduction in a detrimental factor would be an improvement relative to a non-adjusted state. Regarding the particular values which are newly claimed, Degani is newly relied upon which teaches that interstitial fluid pressures in tumors can be from 10-50 mmHg which includes the claimed range, and it would have been obvious given the teachings of Multhoff to have adjusted the vessel pressure to be in this range, which would be a reduction in pressure if the initial pressure in the vessel were above the interstitial fluid pressure, such as if the balloons of Gerrans were moved closer together upon inflation to increase pressure.
Thus, Applicant’s arguments are respectfully found unpersuasive and the claims are rejected as indicated in the body of the rejection above.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL J MARRISON whose telephone number is (703)756-1927. The examiner can normally be reached M-F 7:00a-3:30p ET.
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/SAMUEL J MARRISON/Examiner, Art Unit 3783 /EMILY L SCHMIDT/Primary Examiner, Art Unit 3783
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