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 .
Specification
The abstract of the disclosure is objected to because:
-The examiner recommends adding further punctuation and separating clauses in the abstract to avoid run-on sentences.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 1, 4, 29, 32, 33, 34, 38 are objected to because of the following informalities:
-Claim 1 recites “the implanted tumor tissue” in line 5. Examiner recommends amending to –the implanted sample of tumor tissue—
-Claim 4 recites “the activation energy inside” in lines 7-8. Examiner recommends amending to –the activation energy in situ inside—
-Claim 29 recites “the difficult to access tumor, induced metastatic tumor” in lines 2-3. Examiner recommends amending to –the difficult to access tumor, the induced metastatic tumor—
-Claim 32 recites “the activation energy” in line 2. Examiner recommends amending to –the activation energy in situ—
-Claim 32 recites “coadministered” in line 5. Examiner recommends amending to –co-administered—
-Claim 33 recites “the activation energy” in line 2. Examiner recommends amending to –the activation energy in situ—
-Claim 34 recites “the activation energy” in lines 2 and 3. Examiner recommends amending to –the activation energy in situ—
-Claim 38 recites “the activation energy” in line 2. Examiner recommends amending to –the activation energy in situ—
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-42 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
-Claim 1 recites “difficult to access/treat tumor” in lines 1-2 and 3. It is unclear whether this limitation requires that the tumor is difficult to access and difficult to treat or whether only one of these limitations is required by the claim.
-The term “readily accessible” in claim 1 is a relative term which renders the claim indefinite. The term “readily accessible” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what is required per this limitation.
-Claim 1 recites “in such a manner” in line 5. It is unclear what is meant by this limitation. Further clarification should be provided to identify what manner is required by this limitation.
-Claim 1 recites “the difficult to access/treat tumor site” in line 11. There is insufficient antecedent basis for this limitation in the claim.
-Claim 1 recites “further treats the difficult to access…site” in line 11. It is unclear how the autovaccine response further treats the aforementioned site since treatment of this site was not previously mentioned. The limitations regarding a treatment site include implantation into a readily accessible site in lines 4-5. Further clarification should be provided.
-Claim 4 recites “an activation energy” in line 4. It is unclear whether this the same or different from an activation energy recited in claim 1, line 8. Further clarification should be provided.
-Claim 4 recites “the growing metastatic tumor” in line 6. There is insufficient antecedent basis for this limitation in the claim.
-Claim 6 recites “after an initial treatment of the induced metastatic tumor” in line 3. It is unclear when the step or step(s) recited in this claim occur since no steps in regards to these limitations were previously recited. Further clarification should be provided.
-Claim 7 recites “an initial treatment” in line 2. It is unclear whether this is the same or different from an initial treatment originally referenced in claim 6, line 3. Further clarification should be provided.
-Claim 8 recites “an initial treatment” in line 2. It is unclear whether this is the same or different from an initial treatment originally referenced in claim 6, line 3. Further clarification should be provided.
-Claim 9 recites “an initial treatment” in line 2. It is unclear whether this is the same or different from an initial treatment originally referenced in claim 6, line 3. Further clarification should be provided.
-Claim 9 recites “the growing metastatic tumor” in line 2. There is insufficient antecedent basis for this limitation in the claim. It is also unclear whether or not this is referring to the induced metastatic tumor originally referenced in claim 1, lines 5-6.
-Claim 10 recites “an initial treatment” in line 2. It is unclear whether this is the same or different from an initial treatment originally referenced in claim 6, line 3. Further clarification should be provided.
-Claim 11 recites “the radiation dose” in line 2. There is insufficient antecedent basis for this limitation in the claim.
-Claim 11 recites “initial values” in line 3. It is unclear what these initial values are in reference to. Further clarification should be provided to identify whether these are referring to the radiation dose of an initial treatment, concentrations of the initial treatment, concentrations of the booster treatment or a separate embodiment.
-Claim 14 recites “booster treatments” in line 2. It is unclear whether or not this is the same or different from the booster treatment originally referenced in claim 6, line 2. Further clarification should be provided.
-Claim 14 recites “a period between booster treatments” in lines 1-2. It is unclear when this period occurs since multiple booster treatments were not previously recited and the timing of these treatments was not introduced. Further clarification should be provided to identify when this period between booster treatments occurs.
-The term “palliative level” in claims 15-18, 20, 22, 28 is a relative term which renders the claim indefinite. The term “palliative level” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term palliative level generally means improving quality of life for a patient with serious illness(es); however, this does not identify what exactly is required by the claim. Further clarification should be provided.
-The term “therapeutic level” in claims 15-17, 30, 31 is a relative term which renders the claim indefinite. The term “palliative level” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term therapeutic level generally means improving symptoms for a patient; however, this does not identify what exactly is required by the claim. Further clarification should be provided.
-Claim 16 recites “a palliative or therapeutic level” in line 2. It is unclear whether this is the same or different from a palliative level or therapeutic level originally introduced in claim 15, line 2.
-Claim 16 recites “said phosphors” in line 4. There is insufficient antecedent basis for this limitation in the claim.
-Claim 16 recites “said applying an initiation energy to the induced metastatic tumor” in lines 4-5. There is insufficient antecedent basis for this limitation in the claim.
-Claim 16 recites “after an initial treatment with said phosphors” in line 4. It is unclear when the step or step(s) recited in this claim occur since no steps in regards to these limitations were previously recited. Further clarification should be provided.
-Claim 17 recites “or as part of a supplemental treatment at least one of” in line 2. It is unclear what this limitation requires per the recitation including the supplemental treatment. Further clarification should be provided. It is possibly this should read –or as part of a supplemental treatment with at least one of—
-The term “radiation induced cell kill level” in claims 17, 19, 23 is a relative term which renders the claim indefinite. The term “radiation induced cell kill level” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term radiation induced cell kill level generally means a level of radiation applied to cells to cause or induce death to the cells; however, this does not identify what exactly is required by the claim and does not define the conditions involved in cell death by radiation. Further clarification should be provided.
-Claim 20 recites “after an initial treatment with said phosphors” in lines 2-3. It is unclear when the step or step(s) recited in this claim occur since no steps in regards to these limitations were previously recited. Further clarification should be provided.
-Claim 20 recites “prior to a subsequent booster treatment with said phosphors” in line 4. It is unclear when the recited step occurs since no steps in regards to this limitation were previously recited.
-Claim 21 recites “after an initial treatment with said phosphors” in line 2. It is unclear when the step or step(s) recited in this claim occur since no steps in regards to these limitations were previously recited. Further clarification should be provided.
-Claim 21 recites “the human or animal body” in lines 3-4. There is insufficient antecedent basis for this limitation in the claim.
-Claim 22 recites “after an initial treatment with said phosphors” in line 2. It is unclear when the step or step(s) recited in this claim occur since no steps in regards to these limitations were previously recited. Further clarification should be provided.
-Claim 23 recites “after an initial treatment with said phosphors” in line 2. It is unclear when the step or step(s) recited in this claim occur since no steps in regards to these limitations were previously recited. Further clarification should be provided.
-Claim 24 recites “said auto-vaccine effect” in line 3. There is insufficient antecedent basis for this limitation in the claim. Should possibly read –said auto-vaccine response—
-Claim 27 recites “said auto-vaccine effect” in line 1. There is insufficient antecedent basis for this limitation in the claim. Should possibly read –said auto-vaccine response—
-Claim 32 recites “the absence of an added energy modulation agent” in lines 4-5. There is insufficient antecedent basis for this limitation in the claim.
-Claim 32 recites “the presence of one or more coadministered energy modulation agents” in lines 5-6. There is insufficient antecedent basis for this limitation in the claim.
-Claim 37 recites “the pharmaceutical carrier” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
-Claim 38 recites “the cells of the induced metastatic tumor” in line 5. There is insufficient antecedent basis for this limitation in the claim.
-Claim 38 recites “receiving an initiation energy” in line 3. It is unclear when the step or step(s) recited in this claim occur since no steps in regards to these limitations were previously recited. Further clarification should be provided.
-The term “close proximity” in claims 40 and 41 is a relative term which renders the claim indefinite. The term “close proximity” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is not clear what close proximity encompasses in terms of the scope of the claim. Further clarification should be provided.
-The term “undue and/or dangerous pressure” in claim 42 is a relative term which renders the claim indefinite. The term “undue and/or dangerous” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is not clear what undue and/or dangerous encompasses in terms of the scope of the claim. Further clarification should be provided.
-The term “anatomically dangerous body element” in claim 42 is a relative term which renders the claim indefinite. The term “anatomically dangerous body element” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is not clear what undue and/or dangerous encompasses in terms of the scope of the claim. Further clarification should be provided.
-Claim 42 recites “the infusing into the difficult to access/treat tumor” in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claim(s) 1, 2, 34, 39, 40, 41, 42 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen (WO 2018044888).
Regarding Claim 1, Chen teaches a method for treating a difficult to access/treat tumor in a subject [Pg. 25, lines 27-30]—discloses the use of the methodologies to treat tumors invading nerves, blood vessels, brain and spinal cord, comprising: removing a sample of tumor tissue from the difficult to access/treat tumor [Pg. 18, lines 7-8; “the harvesting assembly 210 allows for repeated sampling from the treated tumor mass, including sampling from different tumor regions if desired.”]; implanting the sample of tumor tissue to a site in the subject that is readily accessible [Pg. 13, lines 25-30]—reference to implanting in the dermis…augmented locally…factor).” (interpreted as readily accessible), in such a manner that the implanted tumor tissue forms an induced metastatic tumor [Pg. 15, lines 9-11] and [Pg. 15, lines 22-23; “In some patients, the vaccination capsule or capsules can be inserted prophylactically into organs that are likely to harbor, or to develop metastases.”]; infusing the induced metastatic tumor with a photoactivatable drug [Pg. 20, lines 3-10]—reference to delivery of photosensitizer solutions to the tumor; and generating an activation energy in situ in the subject sufficient to activate the photoactivatable drug [Pg. 9, lines 28-30]—reference to attaching vaccine dose form to an in situ site, [Pg. 21, lines 28-30]—includes photoactivation of the photothermal sensitizer, thereby activating the photoactivatable drug to treat the induced metastatic tumor and create an autovaccine response [Pg. 22, lines 1-4]—reference to the antitumor immune response by means of photoactivation, and [Pg. 3, lines 25-28]—indicates he treatment approach enables an anti-tumor effect, whereby the autovaccine response further treats the difficult to access/treat tumor site [Pg. 18, lines 18-22]—reference to the tumor being distance from the immunosuppressive tumor microenvironment to allow for enablement of immune response robustness due to less suppression and functionality of the placement of the treated tumor.
Regarding Claim 2, Chen teaches wherein the difficult to access/treat tumor site is a primary tumor [Pg. 25, lines 27-30], [Fig. 11, “brain tissue” and “tumor”], and examples presented in [Pg. 15, lines 24-26]—which include reference to the primary tumor such as lung cancer, prostate cancer, etc.
Regarding Claim 34, Chen teaches wherein generating the activation energy in the subject comprises administering a light emitting device to the subject and causing the light emitting device to emit the activation energy [Pg. 22, lines 18-23]—reference to the light device to deliver light to the tumor substance and activates the photosensitizing drug.
Regarding Claim 39, Chen teaches wherein the difficult to access/treat tumor is a brain tumor [Pg. 25, lines 27-28]—reference to the brain.
Regarding Claim 40, Chen teaches wherein the difficult to access/treat tumor is a tumor in close proximity to a major artery [Pg. 25, lines 27-30]—reference to critical structures including blood vessels and [Pg. 30, lines 27-31].
Regarding Claim 41, Chen teaches wherein the difficult to access/treat tumor is a tumor in close proximity to the subject's spinal cord [Pg. 25, lines 27-30]—reference to critical structures including the spinal cord.
Regarding Claim 42, Chen teaches wherein the difficult to access/treat tumor is in a region of the subject in which the infusing into the difficult to access/treat tumor would create undue and/or dangerous pressure on a nerve, blood vessel, anatomically dangerous body element, and/or organ of the subject [Pg. 25, lines 27-30]—reference to critical structures being treated using disclosed methods as more effective and safer than existing therapies [Pg. 30, lines 27-31].
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 3-33, 35-38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen (WO 2018044888) in view of Bourke (U.S. 20180344850).
Regarding Claim 3, Chen is silent on wherein the difficult to access/treat tumor site is a metastatic tumor. Bourke teaches wherein the difficult to access/treat tumor site is a metastatic tumor [0146]—reference to Avastin administered to FDA approved 6 cancer types including metastatic CRC, NSCLC, mRCC, CC, as well as others.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to characterize the difficult to treat/access tumor as metastatic as taught by Bourke to harvest and provide treatment for as suggested by Chen, as Chen discusses inserting vaccination capsules into organs likely to develop metastases [Pg. 15, lines 22-23] with Bourke because Bourke teaches the use of certain pharmaceuticals to block blood vessel growth to inhibit the feeding of tumors [0146].
Regarding Claim 4, Chen is silent on wherein generating the activation energy in situ in the subject comprises injecting in the induced metastatic tumor a pharmaceutical carrier including one or more phosphorescent or fluorescent agents which are capable of emitting an activation energy in the subject for activating the photoactivatable drug. Bourke teaches wherein generating the activation energy in situ in the subject comprises injecting in the induced metastatic tumor a pharmaceutical carrier including one or more phosphorescent or fluorescent agents which are capable of emitting an activation energy in the subject for activating the photoactivatable drug [0164]—A photoactivatable drug…phosphorescent or fluorescent agents…emitting an activation energy …infuses the first diseased site; and applying an initiation energy to the growing metastatic tumor [0164]—reference to a source of energy generation in situ to activate the drug, whereby the initiation energy is absorbed by the one or more phosphorescent or fluorescent agents, which emit the activation energy inside the induced metastatic tumor [0164]—reference to irradiation of the diseased sites with the initiation energy to initiate activation energy for the phosphorescent or fluorescent agents.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to inject pharmaceutical carriers comprised of phosphorescent or fluorescent agents to cause activation of the photoactivatable drug and emit activation energy to the tumor as taught by Bourke to reduce the tumor’s ability to spread as suggested by Chen, as Chen discusses the use of light activated drug therapies to reduce the tumor’s ability to spread by reducing generation and secretion of immunosuppressive proteins, angiogenic factors, cytokines, small molecules, exosomes and other immune modulating substances [Pg. 3, lines 21-] with Bourke because Bourke teaches the use of this activation and initiation energy to provide immune system stimulation in the body [0164].
Regarding Claim 5, Chen is silent on wherein applying an initiation energy comprises providing a controlled radiation dose of x-ray or high energy electrons to the induced metastatic tumor. Bourke teaches wherein applying an initiation energy comprises providing a controlled radiation dose of x-ray or high energy electrons to the induced metastatic tumor [0192]—reference to first energy source comprising controlled radiation dose of x-rays or high energy electrons.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to deliver radiation to apply energy to the tumor as taught by Bourke to treat tumor cells as suggested by Chen, as Chen discusses delivering radiation or UV light to tumor cells to prepare ex vivo cells [Pg. 4, lines 17-19] with Bourke because Bourke teaches the phosphors absorbing and down converting x-ray energy to radiate as UV light to activate a photoactivatable drug at a diseased site [0032].
Regarding Claim 6, Chen is silent on further comprising providing a booster treatment to the induced metastatic tumor, before, during and/or after an initial treatment of the induced metastatic tumor. Bourke teaches further comprising providing a booster treatment to the induced metastatic tumor, before, during and/or after an initial treatment of the induced metastatic tumor [0100; “Since the goal of the “booster treatments”….after completion of all the primer treatments, between primer treatments…or prior to the primer treatments…once performed.”]
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide booster treatments as taught by Bourke to repeatedly provide treatment and methodology steps as suggested by Chen, as Chen discusses repeatedly sampling the tumor site to overcome a “one size fits all” approach with cancer vaccines [Pg. 18, lines 6-11] with Bourke because Bourke teaches this prime-boost strategy to ensure establishing greater levels of immunity [0101].
Regarding Claim 7, Chen is silent on wherein said booster treatment is performed before an initial treatment of the induced metastatic tumor. Bourke teaches wherein said booster treatment is performed before an initial treatment of the induced metastatic tumor [0100]—reference to prior to primer treatments.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide booster treatments prior to initial treatments as taught by Bourke to repeatedly provide treatment and methodology steps as suggested by Chen, as Chen discusses repeatedly sampling the tumor site to overcome a “one size fits all” approach with cancer vaccines [Pg. 18, lines 6-11] with Bourke because Bourke teaches this prime-boost strategy to ensure establishing greater levels of immunity by activating/stimulating/boosting the immune system[0101].
Regarding Claim 8, Chen is silent on wherein said booster treatment is performed during an initial treatment of the induced metastatic tumor. Bourke teaches wherein said booster treatment is performed during an initial treatment of the induced metastatic tumor [0100]—reference to between primer treatments.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide booster treatments prior to initial treatments as taught by Bourke to repeatedly provide treatment and methodology steps as suggested by Chen, as Chen discusses repeatedly sampling the tumor site to overcome a “one size fits all” approach with cancer vaccines [Pg. 18, lines 6-11] with Bourke because Bourke teaches this prime-boost strategy to ensure establishing greater levels of immunity by activating/stimulating/boosting the immune system [0101].
Regarding Claim 9, Chen is silent on wherein said booster treatment is performed after an initial treatment of the growing metastatic tumor. Bourke teaches wherein said booster treatment is performed after an initial treatment of the growing metastatic tumor [0100]—reference to after completion of all the primer treatments.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide booster treatments prior to initial treatments as taught by Bourke to repeatedly provide treatment and methodology steps as suggested by Chen, as Chen discusses repeatedly sampling the tumor site to overcome a “one size fits all” approach with cancer vaccines [Pg. 18, lines 6-11] with Bourke because Bourke teaches this prime-boost strategy to ensure establishing greater levels of immunity by activating/stimulating/boosting the immune system [0101].
Regarding Claim 10, Chen is silent on wherein said booster treatment is repeated on a periodic basis after an initial treatment of the induced metastatic tumor. Bourke teaches wherein said booster treatment is repeated on a periodic basis after an initial treatment of the induced metastatic tumor [0194]-- during a booster treatment repeated on a periodic basis after an initial treatment of the first or second diseased site.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide booster treatments prior to initial treatments as taught by Bourke to repeatedly provide treatment and methodology steps as suggested by Chen, as Chen discusses repeatedly sampling the tumor site to overcome a “one size fits all” approach with cancer vaccines [Pg. 18, lines 6-11] with Bourke because Bourke teaches this prime-boost strategy to ensure establishing greater levels of immunity by activating/stimulating/boosting the immune system [0101].
Regarding Claim 11, Chen is silent on wherein, in the booster treatment, at least one of phosphor concentration, photoactivatable drug concentration, and the radiation dose is increased by a factor of at least two times initial values. Bourke teaches wherein, in the booster treatment, at least one of phosphor concentration, photoactivatable drug concentration, and the radiation dose is increased by a factor of at least two times initial values [0195]—reference to the phosphor concentration, photoactivatable drug concentration and radiation dose increasing by a factor of at least two times initial values.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to design treatment parameters with certain concentration values of phosphors, drugs and radiation dosing as taught by Bourke to guide and control dosing as suggested by Chen, as Chen discusses reducing risk of drug distribution outside of the lesion to be treated [Pg. 22, lines 14-18] with Bourke because Bourke teaches varying dosage of X-ray, psoralen and phosphor [0025].
Regarding Claim 12, Chen is silent on wherein the booster treatment produces psoralen-modified cancer cells or X-ray modified cancer cells. Bourke teaches wherein the booster treatment produces psoralen-modified cancer cells or X-ray modified cancer cells [0102]—reference to psoralen-modified or x-ray modified cancer cells.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize x-ray modified or psoralen modified cancer cells as taught by Bourke to guide and control dosing as suggested by Chen, as Chen discusses varying the amount and type of photosensitizers including psoralens based on tumor volume and location [Pg. 28, lines 1-7] with Bourke because Bourke teaches the use of these modified cancer cells and booster treatments to allow for the patient’s immune response to be more robust than in a single treatment series [0102].
Regarding Claim 13, Chen is silent on wherein the booster treatment produces radiation damaged cancer cells. Bourke teaches wherein the booster treatment produces radiation damaged cancer cells [0197]—reference to booster treatment producing radiation damaged cancer cells.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include production of radiation damaged cancer cells as taught by Bourke as a result of delivered radiation as suggested by Chen, as Chen discusses preparation of tumor lysates by means of irradiation with ionizing radiation [Pg. 4, lines 17-19] with Bourke because Bourke teaches the use of technologies such as beam therapy and chemotherapy that destroy cancer cells and to avoid these technologies in large areas of the body [0139 and 0141].
Regarding Claim 14, Chen is silent on further comprising delaying a period between booster treatments according to a tolerance level of the subject for radiation-modified cells generated during the booster treatment. Bourke teaches further comprising delaying a period between booster treatments according to a tolerance level of the subject for radiation-modified cells generated during the booster treatment [0198].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to delay treatments according to patient specific parameters such as tolerance level as taught by Bourke to positively influence outcomes of treatment as suggested by Chen, as Chen discusses taking into account tolerability of main treatments [Pg. 26, lines 1-23] with Bourke because Bourke teaches tolerance levels of skin and bone factored into safe delivery of the radiation component of the invention [0054].
Regarding Claim 15, Chen is silent on wherein the booster treatment provides radiating the subject at either a palliative level or a therapeutic level. Bourke teaches wherein the booster treatment provides radiating the subject at either a palliative level or a therapeutic level [0098]—reference to radiation level at a palliative or therapeutic level.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to deliver radiation at palliative or therapeutic levels as taught by Bourke to effect the immune system of the patient as suggested by Chen, as Chen discusses the use of the disclosed method to avoid side effects, cost and drawn out treatment methods [Pg. 25, lines 8-15] with Bourke because Bourke teaches this combination of treatment to activate/stimulate/boost the immune response [0098].
Regarding Claim 16, Chen is silent on wherein the radiating the subject at either a palliative or therapeutic level comprises radiating the subject at the induced metastatic tumor, or at a remote site on the subject relative to the induced metastatic tumor, before, during, and/or after an initial treatment with said phosphors, said photoactivatable drug, and said applying an initiation energy to the induced metastatic tumor. Bourke teaches wherein the radiating the subject at either a palliative or therapeutic level comprises radiating the subject at the induced metastatic tumor, or at a remote site on the subject relative to the induced metastatic tumor, before, during, and/or after an initial treatment with said phosphors, said photoactivatable drug, and said applying an initiation energy to the induced metastatic tumor [0098]—reference to treatment at a palliative or therapeutic level, [0228-0229]—reference to radiating at palliative or therapeutic level before, during or after initial treatment with said phosphors, photoactivatable drug and initiating energy, [0235]—reference to the different treatment sites [0146]—reference to the induced metastatic tumor.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to deliver radiation to the induced metastatic tumor at palliative or therapeutic levels before/during or after initial treatment as taught by Bourke to increase the anti-tumor effect as suggested by Chen, as Chen vaccinating at more than one body site and sequentially over a period of time to increase the anti-tumor effect [Pg. 4, lines 25-27] with Bourke because Bourke teaches the timing and treatment levels being design to allow for an initial humoral or cellular immune response, followed by a period of homeostasis [0099].
Regarding Claim 17, Chen is silent on further comprising radiating the subject with a first energy source or as part of a supplemental treatment at least one of a palliative level, a therapeutic level, or a radiation induced cell kill level. Bourke teaches further comprising radiating the subject with a first energy source [Abstract] or as part of a supplemental treatment [Abstract] at least one of a palliative level, a therapeutic level, or a radiation induced cell kill level [0098] and [Claim 55].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to deliver radiation from a first energy source, utilize a supplemental treatment at a palliative or therapeutic level or radiation induced cell kill level as taught by Bourke to avoid long term side effects of standard therapy as suggested by Chen, as Chen discusses these therapies involving physical, cognitive and mental conditions that are desired to be avoided [Pg. 25, lines 10-15] with Bourke because Bourke teaches the use of all of these interventions to provide an immune system stimulation in the body [Abstract].
Regarding Claim 18, Chen is silent on wherein said radiating the subject comprises radiating at said palliative level. Bourke teaches wherein said radiating the subject comprises radiating at said palliative level [0098].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to deliver radiation at palliative levels as taught by Bourke to effect the immune system of the patient as suggested by Chen, as Chen discusses the use of the disclosed method to avoid side effects, cost and drawn out treatment methods [Pg. 25, lines 8-15] with Bourke because Bourke teaches this combination of treatment to activate/stimulate/boost the immune response [0098].
Regarding Claim 19, Chen is silent on wherein said radiating the subject comprises radiating at said radiation induced cell kill level. Bourke teaches wherein said radiating the subject comprises radiating at said radiation induced cell kill level [0100]—reference to radiation induced cell kill level.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to deliver radiation from a first energy source, utilize a supplemental treatment at a palliative or therapeutic level or radiation induced cell kill level as taught by Bourke to avoid long term side effects of standard therapy as suggested by Chen, as Chen discusses these therapies involving physical, cognitive and mental conditions that are desired to be avoided [Pg. 25, lines 10-15] with Bourke because Bourke teaches the use of all of these interventions to provide an immune system stimulation in the body [Abstract].
Regarding Claim 20, Chen is silent on wherein said radiating the subject comprises radiating at said palliative level as an intervening treatment after an initial treatment with said phosphors, said photoactivatable drug, and said applying initiation energy to the induced metastatic tumor and prior to a subsequent booster treatment with said phosphors, said photoactivatable drug, and said applying initiation energy to the induced metastatic tumor. Bourke teaches wherein said radiating the subject comprises radiating at said palliative level as an intervening treatment after an initial treatment with said phosphors, said photoactivatable drug, and said applying initiation energy to the induced metastatic tumor and prior to a subsequent booster treatment with said phosphors, said photoactivatable drug, and said applying initiation energy to the induced metastatic tumor [0100]—providing intervening treatments between prime and boost states, [0235]—reference to applying said intervening treatment to the first diseased site which is interpreted to be the induced metastatic tumor.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ the use of intervening treatments as taught by Bourke to prevent growth and spread of the tumor as suggested by Chen as Chen discusses the use of light activated drug therapies to reduce the tumor’s ability to spread by reducing generation and secretion of immunosuppressive proteins, angiogenic factors, cytokines, small molecules, exosomes and other immune modulating substances [Pg. 3, lines 21-] with Bourke because Bourke teaches the use of intervening treatments to stunt tumor growth [0100].
Regarding Claim 21, Chen is silent on wherein the method further comprises, before, during, and/or after an initial treatment with said phosphors, said photoactivatable drug, and said applying initiation energy to the induced metastatic tumor, radiating the human or animal body at a region different from the induced metastatic tumor. Bourke teaches wherein the method further comprises, before, during, and/or after an initial treatment with said phosphors, said photoactivatable drug, and said applying initiation energy to the induced metastatic tumor, radiating the human or animal body at a region different from the induced metastatic tumor [0164]—reference to delivering the drug or radiation to the body at the second diseased site interpreted to be the region different from the induced metastatic tumor, [0236; “before, during, and/or after an initial treatment with said phosphors, said photoactivatable drug, and said applying initiation energy, radiating the human or animal body at a region different from the first or second diseased site(s).”] and [0095].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to deliver radiation to a site different from the induced metastatic tumor as taught by Bourke to increase the anti-tumor effect as suggested by Chen, as Chen vaccinating at more than one body site and sequentially over a period of time to increase the anti-tumor effect [Pg. 4, lines 25-27] with Bourke because Bourke teaches the use of these methods to provide immune stimulation in the body [0164].
Regarding Claim 22, Chen is silent on wherein the method further comprises, before, during, and/or after an initial treatment with said phosphors, said photoactivatable drug, and said applying initiation energy to the induced metastatic tumor, radiating the subject with a palliative level of radiation at a region different from the induced metastatic tumor. Bourke teaches wherein the method further comprises, before, during, and/or after an initial treatment with said phosphors, said photoactivatable drug, and said applying initiation energy to the induced metastatic tumor, radiating the subject with a palliative level of radiation at a region different from the induced metastatic tumor [0237]—reference to delivery of radiation to a region different from the first or second diseased site, [Claim 60]—reference to before, during, and/or after an initial treatment….radiation the human or animal body…different region from the second diseased site.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to deliver radiation at a palliative level to a site different from the induced metastatic tumor as taught by Bourke to effect the immune system of the patient as suggested by Chen, as Chen discusses the use of the disclosed method to reduce discomfort and other complications [Pg. 5, lines 6-8] with Bourke because Bourke teaches this combination of treatment to activate/stimulate/boost the immune response [0098].
Regarding Claim 23, Chen is silent on wherein the method further comprises, before, during and/or after an initial treatment with said phosphors, said photoactivatable drug, and said applying initiation energy to the induced metastatic tumor, radiating the subject with a radiation induced cell kill level of radiation at a region different from the induced metastatic tumor. Bourke teaches wherein the method further comprises, before, during and/or after an initial treatment with said phosphors, said photoactivatable drug, and said applying initiation energy to the induced metastatic tumor, radiating the subject with a radiation induced cell kill level of radiation at a region different from the induced metastatic tumor [0100] and [0238].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to deliver radiation at a radiation induced cell kill level as taught by Bourke to avoid long term side effects of standard therapy as suggested by Chen, as Chen discusses these therapies involving physical, cognitive and mental conditions that are desired to be avoided [Pg. 25, lines 10-15] with Bourke because Bourke teaches the use of all of these interventions to provide an immune system stimulation in the body [Abstract].
Regarding Claim 24, Chen is silent on further comprising stunting growth of the difficult to access/treat tumor in the subject until the activated photoactivatable drug causes said auto-vaccine effect in the subject. Bourke teaches further comprising stunting growth of the difficult to access/treat tumor in the subject until the activated photoactivatable drug causes said auto-vaccine effect in the subject [0240].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use treatments to stunt growth of the tumor until the photoactivatable drug causes said auto-vaccine effect as taught by Bourke to prevent growth and spread of the tumor as suggested by Chen as Chen discusses the use of light activated drug therapies to reduce the tumor’s ability to spread by reducing generation and secretion of immunosuppressive proteins, angiogenic factors, cytokines, small molecules, exosomes and other immune modulating substances [Pg. 3, lines 21-] with Bourke because Bourke teaches the use of intervening treatments to stunt tumor growth [0100].
Regarding Claim 25, Chen is silent on further comprising actively stimulating said autovaccine response in the subject by performance of a booster treatment. Bourke teaches further comprising actively stimulating said autovaccine response in the subject by performance of a booster treatment [0098; “The purpose of any of these "booster" treatments is to activate/stimulate/boost the immune response initially or originally generated within the patient during the initial treatments.”]
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide booster treatments to stimulate auto-vaccine response as taught by Bourke to repeatedly provide treatment and methodology steps as suggested by Chen, as Chen discusses repeatedly sampling the tumor site to overcome a “one size fits all” approach with cancer vaccines [Pg. 18, lines 6-11] with Bourke because Bourke teaches this prime-boost strategy to ensure establishing greater levels of immunity [0101].
Regarding Claim 26, Chen is silent on wherein the booster treatment for stimulating said auto-vaccine response comprises injecting a vaccine into the subject. Bourke teaches wherein the booster treatment for stimulating said auto-vaccine response comprises injecting a vaccine into the subject [0242].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include injecting a vaccine into the subject as taught by Bourke to maximize antitumor immune response as suggested by Chen, as Chen discusses optimizing vaccination adjuvants, enhancers, application methods, vaccination sites to reduce systemic side effects and provide greater likelihood of a useful clinical response [Pgs. 7-8, lines 28-5] with Bourke because Bourke teaches these methods to push cellular immune response over certain thresholds required to fight specific pathogens or cells containing tumor specific antigens [0101].
Regarding Claim 27, Chen is silent on wherein stimulating said auto-vaccine effect comprises injecting a tetanus vaccine into the subject. Bourke teaches wherein stimulating said auto-vaccine effect comprises injecting a tetanus vaccine into the subject [0104], [0210] and [0243].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include injecting a tetanus vaccine into the subject as taught by Bourke to maximize antitumor immune response as suggested by Chen, as Chen discusses optimizing vaccination adjuvants, enhancers, application methods, vaccination sites to reduce systemic side effects and provide greater likelihood of a useful clinical response [Pgs. 7-8, lines 28-5] with Bourke because Bourke teaches the use of a conventional vaccine, such as tetanus, to help vaccines in the subject migrate to the lymph nodes, activating an immune response [0104].
Regarding Claim 28, Chen is silent on further comprising radiating the subject with a palliative level of radiation. Bourke teaches further comprising radiating the subject with a palliative level of radiation [0098]—reference to radiation level at a palliative or therapeutic level.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to deliver radiation at palliative or therapeutic levels as taught by Bourke to effect the immune system of the patient as suggested by Chen, as Chen discusses the use of the disclosed method to avoid side effects, cost and drawn out treatment methods [Pg. 25, lines 8-15] with Bourke because Bourke teaches this combination of treatment to activate/stimulate/boost the immune response [0098].
Regarding Claim 29, Chen is silent on further comprising directing radiation to at least one of the difficult to access tumor, induced metastatic tumor, or elsewhere in the body. Bourke teaches further comprising directing radiation to at least one of the difficult to access tumor, induced metastatic tumor, or elsewhere in the body [0200] and [0245],
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to deliver radiation to apply energy to the tumor as taught by Bourke to treat tumor cells as suggested by Chen, as Chen discusses delivering radiation or UV light to tumor cells to prepare ex vivo cells [Pg. 4, lines 17-19] with Bourke because Bourke teaches blocking cancer cell growth using radiation therapy [0138].
Regarding Claim 30, Chen is silent on further comprising providing a therapeutic drug as an immune system stimulant. Bourke teaches further comprising providing a therapeutic drug as an immune system stimulant [0164].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a therapeutic drug as taught by Bourke to reduce the tumor’s ability to spread as suggested by Chen, as Chen discusses the use of light activated drug therapies to reduce the tumor’s ability to spread by reducing generation and secretion of immunosuppressive proteins, angiogenic factors, cytokines, small molecules, exosomes and other immune modulating substances [Pg. 3, lines 21-] with Bourke because Bourke teaches the use of this activation and initiation energy to provide immune system stimulation in the body [0164].
Regarding Claim 31, Chen is silent on wherein the therapeutic drug comprises a vaccine. Bourke teaches wherein the therapeutic drug comprises a vaccine [0209].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select a vaccine as the therapeutic drug as taught by Bourke to maximize antitumor immune response as suggested by Chen, as Chen discusses optimizing vaccination adjuvants, enhancers, application methods, vaccination sites to reduce systemic side effects and provide greater likelihood of a useful clinical response [Pgs. 7-8, lines 28-5] with Bourke because Bourke teaches these methods to push cellular immune response over certain thresholds required to fight specific pathogens or cells containing tumor specific antigens [0101].
Regarding Claim 32, Chen is silent on wherein generating the activation energy comprises applying an initiation energy selected from x- rays, gamma rays, electron beams and proton beams, whereby the initiation energy is converted into the activation energy in situ within the subject in the absence of an added energy modulation agent, or in the presence of one or more coadministered energy modulation agents. Bourke teaches wherein generating the activation energy comprises applying an initiation energy selected from x- rays, gamma rays, electron beams and proton beams [0192]—reference to the use of x-rays as the initiation energy from the first source, whereby the initiation energy is converted into the activation energy in situ within the subject in the absence of an added energy modulation agent, or in the presence of one or more coadministered energy modulation agents [0032]—reference to psoralen combined with phosphors that absorb and down-convert x-ray energy to re-radiate as UV light or other light.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to deliver radiation to apply energy to the tumor as taught by Bourke to treat tumor cells as suggested by Chen, as Chen discusses delivering radiation or UV light to tumor cells to prepare ex vivo cells [Pg. 4, lines 17-19] with Bourke because Bourke teaches the use of low x-ray doses to avoid tissue damage from radiation [0032].
Regarding Claim 33, Chen is silent on wherein the initiation energy is converted into the activation energy in the subject in the absence of an added energy modulation agent. Bourke teaches wherein the initiation energy is converted into the activation energy in the subject in the absence of an added energy modulation agent [0057]—reference to absence of phosphors and x-ray radiation with the use of a UV lamp and [0032]—with reference to down-converting x-ray energy to re-radiate as UV light.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to enable initiation energy to convert to activation energy without the use of an energy modulation agent as taught by Bourke to treat tumor cells as suggested by Chen, as Chen discusses delivering UV light to tumor cells to prepare ex vivo cells [Pg. 4, lines 17-19] with Bourke because Bourke teaches the use of la UV lamp to activate a photoactivatable drug [0032].
Regarding Claim 35, Chen is silent on wherein the pharmaceutical carrier including the one or more phosphorescent or fluorescent agents also comprises the photoactivatable drug, such that the photoactivatable drug and the one or more phosphorescent or fluorescent agents are co-infused to the induced metastatic tumor. Bourke teaches wherein the pharmaceutical carrier including the one or more phosphorescent or fluorescent agents also comprises the photoactivatable drug, such that the photoactivatable drug and the one or more phosphorescent or fluorescent agents are co-infused to the induced metastatic tumor [0038]—reference the photoactivatable drug being selected from a groups of phosphorescent or fluorescent agents including psoralens, and [0094]—which discusses first pharmaceutically acceptable carrier and one or more phosphorescent or fluorescent agents and photoactivatable drug being co-infused into the diseased site.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to co-infuse the phosphorescent or fluorescent agents and the photoactivatable drug as taught by Bourke to slow the clearance of the photosensitizer from the tumor mass as suggested by Chen, as Chen discusses co-injecting the photosensitizers, embolic material and other solutions to prolong the high concentration of photoactive drug and speed up the light activation process [Pg. 24, lines 13-19] with Bourke because Bourke teaches the relationship of the initiation and activation agents on the treatment process to the first diseased site [0094].
Regarding Claim 36, Chen is silent on wherein the pharmaceutical carrier including the one or more phosphorescent or fluorescent agents is sequentially administered into the induced metastatic tumor before or after infusing the induced metastatic tumor with the photoactivatable drug. Bourke teaches wherein the pharmaceutical carrier including the one or more phosphorescent or fluorescent agents is sequentially administered into the induced metastatic tumor before or after infusing the induced metastatic tumor with the photoactivatable drug [0160]—reference to administration of the energy modulation agent (interpreted to be the phosphorescent or fluorescent agents) before or after infusing the activatable pharmaceutical agent.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select the timing and order of administration of the energy modulation agents and the pharmaceutical agents as taught by Bourke to slow the clearance of the photosensitizer from the tumor mass as suggested by Chen, as Chen discusses co-injecting the photosensitizers, embolic material and other solutions to prolong the high concentration of photoactive drug and speed up the light activation process [Pg. 24, lines 13-19] with Bourke because Bourke teaches employing different variations of the disclosed limitation based on absorption rate, localization and molecular trafficking properties of the agents [0160].
Regarding Claim 37, Chen is silent on wherein the pharmaceutical carrier including the one or more phosphorescent or fluorescent agents is simultaneously administered into the induced metastatic tumor while infusing the induced metastatic tumor with the photoactivatable drug. Bourke teaches wherein the pharmaceutical carrier including the one or more phosphorescent or fluorescent agents is simultaneously administered into the induced metastatic tumor while infusing the induced metastatic tumor with the photoactivatable drug [0038]—reference the photoactivatable drug being selected from a groups of phosphorescent or fluorescent agents including psoralens, and [0094]—which discusses first pharmaceutically acceptable carrier and one or more phosphorescent or fluorescent agents and photoactivatable drug being co-infused into the diseased site.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to simultaneously co-infuse the phosphorescent or fluorescent agents and the photoactivatable drug as taught by Bourke to slow the clearance of the photosensitizer from the tumor mass as suggested by Chen, as Chen discusses co-injecting the photosensitizers, embolic material and other solutions to prolong the high concentration of photoactive drug and speed up the light activation process [Pg. 24, lines 13-19] with Bourke because Bourke teaches the relationship of the initiation and activation agents on the treatment process to the first diseased site [0094].
Regarding Claim 38, Chen is silent on wherein generating the activation energy in the subject comprises modifying cells of the sample of tumor tissue to be fluorescent upon receiving an initiation energy, and, after implanting to form the induced metastatic tumor, applying the initiation energy to the induced metastatic tumor to cause fluorescence from the cells of the induced metastatic tumor. Bourke teaches wherein generating the activation energy in the subject comprises modifying cells of the sample of tumor tissue to be fluorescent upon receiving an initiation energy, and, after implanting to form the induced metastatic tumor, applying the initiation energy to the induced metastatic tumor to cause fluorescence from the cells of the induced metastatic tumor [0165; “photoactivatable drug…first diseased site].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include modification of cells to be fluorescent upon receiving an initiation energy, and, after implanting to form the induced metastatic tumor, applying the initiation energy to the induced metastatic tumor to cause fluorescence from the cells of the induced metastatic tumor as taught by Bourke to reduce the tumor’s ability to spread as suggested by Chen, as Chen discusses the use of light activated drug therapies to reduce the tumor’s ability to spread by reducing generation and secretion of immunosuppressive proteins, angiogenic factors, cytokines, small molecules, exosomes and other immune modulating substances [Pg. 3, lines 21-] with Bourke because Bourke teaches the use of this activation and initiation energy to provide immune system stimulation in the body [0164].
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
-Chen (U.S. 20170246472)-discloses a cytotoxic photoactivation process to treat abnormal tissues including cancer
-Rabizadeh (U.S. 11590217)-references protocols related to compositions for cancer immunotherapy that utilize vaccine and immune modulators
-Lewandowski (WO 03049801)-discusses use of light sensitive compounds in cancer therapies
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/B.N.K./Examiner, Art Unit 3791
/CHRISTINE H MATTHEWS/Primary Examiner, Art Unit 3791