DETAILED ACTION
Applicants’ arguments, filed May 11, 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Status
Claim 11 is canceled.
Claims 1-10 and 12-17 are pending and under examination.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
Claim 17 is drawn to an apparatus comprising a single use cassette, the single use cassette comprising a means for passing a saline or buffered solution through a syringe filter in an opposite direction of a trapping movement. The examiner interprets the use of “means for” at the start of the last paragraph of this claim to invoke 112(f). Thus, the scope of this feature in the single use is interpreted to be limited by the description provided in the specification. However, as described below in an associated 112(b) rejection below, the examiner concludes that no such description of this means is provided in the specification.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 17 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In this case, claim 17 is drawn to an apparatus comprising a radiometal generator, a reactor, a syringe filter membrane, and a means for passing saline or buffered solution through the syringe filter in a direction opposite of a trapping movement. This is a newly introduced independent claim. The applicant states in the reply filed May 11, 2026 that claim 17 is unlike claim 1 in that it is drawn to an apparatus, not a method; but also states that support for new claim 17 can be found in the claims of the application as filed. The examiner notes that no prior claim set in the prosecution history of this application contains claims drawn to an apparatus, so it appears that the applicant is stating that support for newly added claim 17 is the new claim itself. Furthermore, the examiner notes that the specification provides no description of apparatuses or devices containing these components. Examples 1 and 2 of the instant specification describe manual syringe filter based purification methods outside the confines of an apparatus. While examples 3-11 describe using an automated synthesizer with a syringe filter placed on the single-use cassette, this example lacks meaningful detail regarding the structure of said apparatus and is silent regarding a means for passing saline or buffered solution through the syringe filter in a direction opposite of a trapping movement. Therefore, the examiner concludes that there is insufficient written description for such an apparatus as claimed in new claim 17 to convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention. Furthermore, as this claimed invention was not previously set forth or disclosed, the examiner understands it to constitute new matter. Therefore, claim 17 is rejected under 35 U.S.C. 112(a).
Claim Rejections - 35 USC § 112(b)
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 16 and 17 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 16 in its current form depends upon claim 11, which is a canceled claim. Thus, it is unclear what the full scope of claim 16 is. Claim 16 could alternatively depend from any of the previously recited claims 1-10 and 12-15. However, as claims 1-10 and 12-15 have different scopes from each other, should claim 16 depend from any of these claims, each possible resulting claim would possess a different scope. Therefore, claim 16 is considered indefinite. For the purpose of examination, the examiner will interpret claim 16 to depend from claim 1.
Regarding claim 17, the claim limitation “means for passing a saline or buffered solution through the syringe filter in an opposite direction of a trapping movement as a final bulk solution” invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. The disclosure is devoid of any structure that performs the function in the claim. While the method of examples 3-11 includes using a single use cassette and a syringe filter, no description of a means for passing a buffered solution in an opposite direction of a trapping movement is contemplated or disclosed in the context of a single use cassette. While the figures provide depictions of syringes for passing a buffered solution in an opposite direction of a trapping movement, this is in the context of manually performing the untrapping step, not in the context of a single use cassette in an apparatus. Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-10 and 12-17 are rejected under 35 U.S.C. 103 as being unpatentable over Mueller (Mueller, D.; et al., Appl. Radiat. Isot., 2017 – provided by applicant in IDS filed July 27, 2023) in view of Isabel (Isabel, S.; et al., Appl. Environ. Microbiol., 2011), Mathias (Mathias, C. J.; Green, M. A., Appl. Radiat. Isot., 2008 – provided by applicant in IDS filed July 27, 2020), and Liu (Liu, Z.; et al., React. Chem. Eng., 2020).
Mueller teaches a simple and rapid method for the preparation of 68Ga-radiolabeled macroaggregated human serum albumin (MAA) (pg. 72, Abstract). Mueller teaches similar manual (pg. 73, Section 2.1; and pg. 74, Fig. 2) and automated (pg. 73-75, Section 2.2; and pg. 75, Fig. 3 and Fig. 4) methods for the preparation of 68Ga-labeled MAA. In the automated method of Mueller, a 68Ga generator is used to provide 68Ga radiometal (pg. 74, section 2.2, right column text). The 68Ga is then purified on an SCX cartridge. The method of Mueller continues with the synthesis of radiolabeled MAA from the MAASOL kit using the radiometal generator eluate and transfer of the product to a final vial (Section 2.2). Mueller describes that the automated synthesis method resulted in a labeling efficiency of >99% and the synthesis was able to be performed within 14 minutes (pg. 75, Section 2.2).
Mueller does not teach passing a bulk solution containing synthesized radiolabeled MAA particles and impurities on a syringe filter membrane and untrapping the radiolabeled MAA particles using a saline or buffered solution passing through the syringe filter in an opposite direction of a trapping movement. Mueller also does not teach maintaining the generator eluate at room temperature for 2-30 minutes or heated at 40-80°C for 2-20 minutes before trapping the generator eluate on the syringe filter.
Isabel teaches a method of using syringe filters to isolate Bacillus spores (pg. 1507, Fig. 1). In step 7 of this protocol, a solution containing the spores is passed through a single-use 0.45 µm PVDF syringe filter and the spores are retained in the filter while the other components of the solution are not retained. In step 8, the spores were untrapped from the syringe filter by passing liquid through the syringe filter in the direction opposite to the flow of liquid in step 7. Isabel states that simply inverting the flow direction enabled efficient recovery of spores (pg. 1511, right column, second paragraph). Isabel teaches that the syringe filter trap and elution method results in improved isolation of spore DNA for PCR (pg. 1510, Table 3). Isabel also states that the syringe filter purification method is easy to perform (pg. 1512, left column, second paragraph).
Mathias teaches a method for the preparation of 68Ga-radiolabeled macroaggregated human serum albumin (MAA) (section 2, paragraphs 2 and 3). Mathias eluted the 68Ga radiometal from a 68Ge/68Ga generator, producing a 68Ga-containing generator eluate. This generator eluate was reacted with MAA particles from a commercially available Pulmolite® kit. Mathias teaches performing the radiolabeling reaction (which contains the generator eluate) at 75°C for 15 minutes (section 2, paragraph 3). The radiolabeled MAA particles were then purified by centrifugation (Section 2, paragraphs 2 and 3). The procedure resulted in a bulk solution injectable to a patient. Mathias further teaches determining radiolabeling yield by passing the synthesized 68Ga-MAA product on a 0.2 µm nylon syringe filter, selectively retaining the 68Ga-MAA (section 2, paragraph 3).
Liu teaches an automated method for the preparation of an Al18F-labeled radioconjugate (pg. 1441, Abstract). Liu describes 18F-labeled peptides to be similar to 68Ga-labeled analogues (pg. 1441, Introduction). The method of Liu involves the generation of 18F in a cyclotron, followed by trapping of 18F on a µQMA anion exchange cartridge and subsequent elution in the reverse direction (pg. 1443, Section 2.1; and pg. 1444, Fig. 2 and Fig. 3). This is followed by the radiolabeling reaction, purification of the radiolabeled product, and preparation of the final product (pg. 1444, Fig. 2). Liu teaches that the automated opposite flow trapping and elution of 18F was enabled by multi-port switch valves (pg. 1443, Section 2.1 and Fig. 1). Liu describes that trapping in one direction and eluting with opposite flow improved elution efficiency (pg. 1443, Section 2.1) and allowed for highly concentrated radionuclide to be obtained in an automated manner (pg. 1444, right column, second paragraph).
A person of ordinary skill in the art would have recognized that both Mueller and Mathias teach methods of preparing 68Ga-radiolabeled MAA particles. It would also be recognized that both Mueller and Liu relate to automated synthesis of radionuclide-containing pharmaceutical compositions. The skilled artisan would also recognize that Mathias teaches purification of 68Ga-radiolabeled MAA after the labeling reaction. It would be recognized that Mathias also teaches that 68Ga-radiolabeled MAA can be separated from impurities by a syringe filter (as was done to assess radiolabeling efficiency). Isabel teaches a similar syringe filter-based method of micron-scale particle isolation that is accompanied by untrapping the particles using opposite flow. It would be recognized that Liu describes opposite flow trapping and elution can be automated.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the 68Ga-MAA preparation protocol of Mueller with syringe filter purification as taught by Isabel because Mathias teaches that syringe filters can be used to trap 68Ga-MAA and Liu teaches that opposite flow trapping and elution is suitable for and useful in automated radiopharmaceutical preparation (MPEP 2143(I)(G)). It would also have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the reaction conditions of Mueller to be performed at 75°C for 15 minutes as taught by Mathias, as these conditions are an equivalent function substitute for those of Mueller that Mathias teaches as successful in preparing the 68Ga-MAA product (MPEP 2143(I)(B)). These modifications would predictably yield a method of radiolabeling MAA particles with 68Ga wherein the bulk crude radiolabeled product is purified by passing the product on a syringe filter and eluting it by flowing buffered solution in the opposite direction and an apparatus for performing this method.
A person of ordinary skill in the art would have had a reasonable expectation of success in incorporating a syringe filter-based purification step in the method of Mueller because Mathias teaches that a syringe filter can selectively retain 68Ga-MAA and not retain other impurities present in a bulk solution. Additionally, Isabel teaches that flowing buffered solution on a syringe filter in the direction opposite of the trapping flow is an effective means of untrapping and eluting particle-like material. Furthermore, Liu teaches that such opposite flow trapping and eluting can be incorporated into automated synthesizers using switch valves. There is also an expectation of success for altering the reaction temperature, as Mathias demonstrates its efficacy for MAA radiolabeling and temperature-controlled reaction vessels are understood to be able to be used at a range of temperatures.
The skilled artisan would have been motivated to add the syringe filter-based purification step to the protocol of Mueller to increase the purity of the final product and make it safer for injection into a subject. The skilled artisan would also have been motivated to select the reaction temperature of Mathias as it is an alternative known in the art and a lower temperature would use less energy.
Regarding claim 1, the 68Ga-MAA preparation protocol of Mueller teaches using a 68Ga radiometal generator to produce a 68Ga radiometal generator eluate, combining the generator eluate with MAA particles from the MAASOL MAA labeling kit, which is a commercially available 99mTc MAA labeling kit (pg. 73, left column, first paragraph), and generating a final bulk solution of 68Ga-MAA in a buffered solution (Section 2.2). Mueller also teaches transferring the final product to a vial (pg. 74, right column). Additionally, Isabel teaches trapping and recovering similar sized particle-like material using a 0.45 µm pore size PVDF syringe filter by trapping using bulk solution flow in one direction followed by untrapping using flow in an opposite direction (pg. 1507, Fig. 1; Spore capture and recovery step; and DARE procedure). Furthermore, the radiolabeling yield measurement method of Mathias teaches the selective retention of 68Ga-MAA on a 0.2 µm nylon syringe filter (section 2, paragraph 3). Additionally, Liu teaches automated opposite flow trapping and elution incorporated into an automated synthesizer using switch valves (pg. 1443, section 2.1; and pg. 1444, Fig. 3). As Mueller teaches the resuspension of MAA particles in the provided buffer, transferring the material to the reaction vial, and adding the generator eluate to this solution (Section 2.2), the passing of this solution onto a syringe filter is understood to be a passing of an entire bulk solution containing synthesized radiolabeled MAA particles ant impurities comprising free radioactive metal isotopes, parent radioactive metal breakthrough, and stannous chloride present in the MAA labeling kit for 99mTc in a trapping movement. Isabel teaches performing untrapping with an opposite direction flow using PBS, which is a buffered solution (pg. 1507, Spore capture and recovery step). The product of this purification would be radiolabeled MAA in a buffered solution, which the examiner considers to read on “solution injectable to the patient.” The automated nature of the method of Section 2.2 of Mueller is understood to read on the “automatable” limitation. Furthermore, Mueller also teaches an analogous manual method in section 2.1 comprising the same essential steps that can be considered to be automated with the automated synthesizer of section 2.2. Therefore, the combined teachings of Mueller, Isabel, Mathias, and Liu render claim 1 obvious.
Regarding claims 2-4, the radiolabeled MAA preparation protocol of Mueller teaches labeling the MAA particles with 68Ga (section 2.2). Therefore, the combined teachings of Mueller, Isabel, Mathias, and Liu render claims 2-4 obvious.
Regarding claims 5-7, Isabel teaches a method of using syringe filters to trap and elute material using a single-use 0.45 µm PVDF syringe filter (pg. 1507, Spore capture and recovery step and DARE procedure). Additionally, the syringe filter method of Mathias teaches that using a 0.2 µm filter will selectively retain 68Ga-MAA (section 2, paragraph 3). Therefore, the combined teachings of Mueller, Isabel, Mathias, and Liu render claims 5-7 obvious.
Regarding claims 8 and 9, the syringe filter method of Mathias does not teach a specific syringe filter membrane diameter. The method of Isabel teaches using a 13 mm diameter filter for the Bacillus spore isolation (pg. 1507, Spore Capture and Recovery Step). Nevertheless, the skilled artisan would have been motivated to optimize the diameter of syringe filter used for the purification of radiolabeled MAA particles to improve final product purity. Therefore, the combined teachings of Mueller, Isabel, Mathias, and Liu render claims 8 and 9 obvious.
Regarding claim 10, the syringe filter method of Mathias teaches that using a 0.2 µm nylon filter will selectively retain 68Ga-MAA (section 2, paragraph 3). Additionally, Isabel teaches a purification method using a 0.45 µm PVDF syringe filter (pg. 1507, Spore capture and recovery step). Therefore, the combined teachings of Mueller, Isabel, Mathias, and Liu render claim 10 obvious.
Regarding claim 12, Mathias teaches the use of a syringe filter to trap 68Ga-MAA (section 2, paragraph 3) and Isabel teaches a method of eluting trapped material from a syringe filter (pg. 1507, Fig. 1). Mueller teaches an automated preparation of 68Ga-MAA using a single-use cassette (section 2.2, pg. 74, Fig. 3). Liu teaches that switch valves enable opposite flow trapping and elution in the automated preparation of radiopharmaceutical compositions (Section 2.1 and pg. 1444, Fig. 3). Combining these teachings would result in a syringe filter being attached to the single-use cassette as the cassette is necessarily used for performing the synthesis of Mueller and purification added by the modification. Therefore, the combined teachings of Mueller, Isabel, Mathias, and Liu render claim 12 obvious.
Regarding claim 13, the radiolabeled MAA preparation protocol of Mathias teaches performing the radiolabeling reaction (which contains the generator eluate) at 75°C for 15 minutes (section 2, paragraph 3). Therefore, the combined teachings of Mueller, Isabel, Mathias, and Liu render claim 13 obvious.
Regarding claim 14, Mueller teaches the use of an automated synthesizer for the production of 68Ga-MAA (section 2.2, pg. 73, bottom paragraph in right column). Additionally, Liu teaches the incorporation of opposite flow trapping and eluting in an automated synthesizer (Section 2.1 and pg. 1444, Fig. 3). Therefore, the combined teachings of Mueller, Isabel, Mathias, and Liu render claim 14 obvious.
Regarding claim 15, Mueller teaches pre-purifying the 68Ga-containing generator eluate on a cationic cartridge and eluting the 68Ga as a pre-purified generator eluate prior to its addition to MAA for the radiolabeling reaction (section 2.2, pg. 74, bottom paragraph in right column). Therefore, the combined teachings of Mueller, Isabel, Mathias, and Liu render claim 15 obvious.
Regarding claim 16, the syringe filter of Isabel comprises a Luer lock (pg. 1507, DARE Procedure). Therefore, the combined teachings of Mueller, Isabel, Mathias, and Liu render claim 16 obvious.
Regarding claim 17, Mueller teaches an apparatus comprising a radiometal generator and a single use cassette comprising a reaction vial, a product vial, switch valves, and a pump (pg. 74, Fig. 3 and Fig. 4). Mueller describes performing the method using the apparatus with a commercially available labeling kit for 99mTc MAA (pg. 73, left column, first paragraph; and section 2.2), so it is interpreted that the apparatus contained the contents of the kit, reading on the limitation requiring the apparatus to comprise the kit. The incorporation of syringe filter purification by trapping and opposite flow elution as taught by Isabel (pg. 1507, Fig. 1) would require the modification of the automated synthesizer single use cassette of Mueller with a syringe filter containing a syringe filter membrane. The apparatus of Mueller contains switch valves and a pump, which in view of Liu, is considered to be a means for passing saline or a buffered solution through the syringe filter in an opposite direction of a trapping movement. Liu teaches that switch valves enable opposite flow trapping and elution in radiopharmaceutical automated synthesizer apparatuses comprising a pump (Section 2.1 and Figs. 1-3). Therefore, the combined teachings of Mueller, Isabel, Mathias, and Liu render claim 17 obvious.
Response to Arguments
In the reply filed May 11, 2026, Applicant puts forth that Mathias, Isabel, and Mueller alone or in combination fail to teach or suggest all the features of amended independent claim 1. Applicant’s arguments filed have been fully considered but they are not persuasive.
First, Applicant asserts that Mathias and Mueller do not teach passing an entire bulk solution containing synthesized radiolabeled MAA particles and impurities comprising free radioactive metal isotopes, parent radioactive metal breakthrough, and stannous chloride present in the MAA labeling kit for 99mTc on a syringe filter membrane and untrapping the radiolabeled MAA particles from the syringe filter using a saline or buffered solution passing through the syringe filter in an opposite direction of a trapping movement as a final bulk solution. Applicant puts forth that Mathias teaches centrifugation as a purification method and Mueller teaches SPE as a purification method. Applicant asserts that due to the centrifugation teaching of Mathias, a person of ordinary skill in the art would have been diverted to think that a further filtration step clearly intended to determine the radiolabeling yield could be used instead of centrifugation or to supplement centrifugation with the same purpose. Applicant also states that neither Mathias nor Mueller teach or suggest a dedicated purification step to remove SnCl2, a dedicated purification step to remove non-aggregated albumin, an alternative to SPE that does not sacrifice yield, a process explicitly oriented toward automation, or a simplified or quicker post-labeling purification. Applicant also asserts that as neither Mathias nor Mueller discusses final purification as being an issue, thus not identifying the problem contemplated by the present application, that the references cannot provide a solution to that problem. Furthermore, Applicant states that Mathias teaches using a syringe filter to determine radiolabeling yield and that this method is not devoted to purification and elimination of impurities. Applicant asserts that the porosity of Mathias’s filter is of no importance, as only large MAA particles have to be trapped. Applicant also puts forth that the method of Mathias is entirely manual.
Second, Applicant asserts that a person of ordinary skill in the art would not have considered Isabel in any attempt to compensate for the deficiencies of Mathias and Mueller. Applicant states that Isabel does not belong to the field of radiochemistry but rather to the field of environmental microbiology, concluding that Isabel is not analogous prior art. Applicant asserts that because the Bacillus spores of Isabel are typically 0.5x1.5 micron in size, the membranes used for retaining the spores should be very different from membranes used to retain 10-150 micron MAA particles. Applicant further states that Isabel discusses biological compounds not related to MAA and that Isabel is silent about procedures concerning radiopharmaceuticals.
Third, Applicant asserts that the final method step of “providing the final bulk solution injectable to the patient into a vial” is not taught or suggested by the Mathias, Mueller, and/or Isabel.
First, respectfully, this argument is not persuasive. In response to applicant's arguments that Mathias and Mueller individually do not teach passing an entire bulk solution on a syringe filter membrane and untrapping the trapped radiolabeled MAA particles in an opposite direction and instead teach SPE and centrifugation, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As described above, Mathias does teach passing a solution comprising radiolabeled MAA particles on a syringe filter in a trapping motion and Isabel teaches trapping and untrapping biological materials on a syringe filter using an opposite flow technique.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a dedicated purification step to remove SnCl2, a dedicated purification step to remove non-aggregated albumin, an alternative to SPE that does not sacrifice yield, a process specifically oriented toward automation, or a simplified or quicker post-labeling purification) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). While purification of radiolabeled MAA particles from stannous chloride and non-aggregated albumin (among other impurities) is required in the claimed method, separate dedicated steps for the removal of each of these impurities is not a requirement of the claim as currently presented. In its current form, the examiner interprets the scope of claim 1 to allow for the removal of all of these impurities in the same step. Accordingly, as described above, the combined teachings of Mueller, Isabel, Mathias, and Liu result in a method which would perform the method as claimed.
With regard to the assertion that the method of Mathias is entirely manual and the argument that Mathias using centrifugation for purification would divert a skilled artisan to think that a further filtration step could be used instead of or in supplement of centrifugation, these arguments are considered moot because the new ground of rejection relies on the method of Mueller as the primary reference (See above). Additionally, purely en arguendo, a method being manual does not prevent the method from being automatable.
With regard to the argument that because Mathias teaches applying a solution of radiolabeled MAA particles on a syringe filter to determine radiolabeling yield, the porosity of Mathias’s filter is of no importance; in the new ground of rejection above, this method of Mathias is used to suggest that syringe filter trapping, as taught by Isabel could work in the context of MAA particles and as a teaching of useful syringe filter parameters for use in such a method. That Mathias does not teach using the syringe filter in a method explicitly defined as purification is not relevant to the use of this reference in the rejection in this way. Additionally, the porosity of Mathias’s filter is indeed pertinent, specifically because it demonstrates the trapping of large MAA particles. This method of Mathias demonstrates that syringe filters can be used to trap radiolabeled MAA particles, isolating them from impurities.
Applicant also argues that because neither Mathias nor Mueller identify final purification as being an issue, the references cannot provide a solution to that problem. The examiner notes that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Furthermore, Mathias and Mueller are cited as relevant references teaching methods and an automated apparatus for the synthesis of 68Ga-labeled MAA, which is in the field of endeavor of the inventor. Additionally, the examiner asserts that Mathias does teach isolation of radiolabeled MAA particles from impurities.
Second, respectfully, this argument is not persuasive. In response to applicant's argument that Isabel is nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, Isabel is considered to be reasonably pertinent to the particular problem with which the inventor was concerned. Isabel teaches a method of isolating micron-scale particle-like materials using a syringe filter. Similarly, a method of purifying radiolabeled MAA particles is described by the applicant to involve isolating 10-150 micron particles. As Isabel can be viewed as a reference in the field of particle-like biological material purification, it is indeed pertinent to the particular problem contemplated in the instant application.
Additionally, regarding the statement that the specifications of the membranes for retaining MAA particles and Bacillus spores should be very different; the examiner respectfully disagrees. In filtration purification, a comparison between filter pore size and size of the material being applied to the filter is the primary determinant of suitability of the filter. Applicant states that Bacillus spores are smaller in size than MAA particles. Therefore, if Bacillus spores are trapped by the 0.45µm syringe filter membrane of Isabel, so would the MAA particles of the instant application. Furthermore, Mathias describes a 0.22 µm filter isolating radiolabeled MAA particles, suggesting that stannous chloride, parent radioactive metal breakthrough, and free radioactive metal isotopes impurities pass through a filter with a 0.22 µm pore size. It would thus follow that these impurities would also pass through a 0.45 µm membrane.
With regard to the assertion that Isabel discusses biological compounds and environmental microbiology and is silent regarding radiopharmaceuticals, metal labelling, radiotracer purification, and radiochemistry, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Furthermore, as described above, Isabel is pertinent art as it relates to particle purification.
Third, respectfully, this argument is not persuasive. As stated in the above rejection, Mueller teaches providing the final product in a vial. As the product of the radiolabeled MAA particles eluted using an opposite flow elution using a buffered solution would be a solution containing MAA particles, this is interpreted to be a solution injectable to a patient being provided into the final vial.
Conclusion
All claims are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/E.P.M./Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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