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 .
Information Disclosure Statement
The information disclosure statement filed on July 27, 2023 is acknowledged and has been considered by the examiner.
Claim Interpretation
The examiner has noted that the applicant recites on page 8 of the specification “A syringe filter is a single-use filter cartridge.” MPEP §2111.01 states “Where an explicit definition is provided by the applicant for a term, that definition will control interpretation of the term as it is used in the claim.” Therefore, the examiner interprets the phrase “syringe filter” recited in claims 1 and 10-13 to refer to a single-use filter cartridge.
Claim 1 recites a method comprising a step in which radiolabeled MAA particles are passed on a syringe filter membrane “…having a membrane composition, diameter, and pore size configured to trap the radiolabeled MAA particles…and not retain impurities…” and further recites that the impurities comprise a specific list of compounds. The examiner interprets that the phrase “configured to” and the following language in this context describe the properties and capabilities of the filter. The examiner thus interprets this section of the claim to mean that the structural requirements of the method step are that the radiolabeled MAA particles are passed over a syringe filter and that the syringe filter possesses the capabilities following the phrase “configured to.” It is interpreted that the claimed method step does not require the specifically listed impurities of “free radioactive metal isotopes, parent radioactive metal breakthrough, and stannous chloride” to pass through said filter in the method of claim 1.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 11 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. In the specification of the application, the applicant defines a syringe filter as being a single-use filter cartridge (see Claim Interpretation). Claim 11 depends on claim 1 and specifies the syringe filter of claim 1 as comprising a single-use filter cartridge. However, as the syringe filter of claim 1 is already interpreted to refer to a single-use filter cartridge, claim 11 fails to specify a further limitation of the subject matter claimed in claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-11, 13, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Mathias (Mathias, C.J.; Green, M.A., Appl. Radiat. Isot., 2008) in view of Isabel (Isabel, S.; et. al., Appl. Environ. Microbiol., 2011).
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. 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).
The synthesis and purification procedures of Mathias fails to teach untrapping the radiolabeled MAA particles from a 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.
A person of ordinary skill in the art would have recognized that the syringe filter method of determining radiolabeling yield of Mathias that selectively retains 68Ga-MAA would also be capable of use in purifying radiolabeled MAA particles. Mathias’s recitation of selective retention teaches that the syringe filter is capable of retaining material in the size range of MAA particles and not retaining impurities such as free radioactive metal isotopes. Furthermore, it would also be recognized that the method of Isabel similarly teaches using a syringe filter to selectively retain micron-scale particles and remove smaller impurities. Isabel additionally provides a method of eluting these trapped species from a syringe filter by flowing liquid in the direction opposite of the trapping step. Applying this same elution step to the trapping of Mathias would enable isolation of the selectively retained 68Ga-MAA.
Therefore, it would have been 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 Mathias with the radiolabeled MAA trapping protocol further taught by Mathias, applying MAA to a syringe filter to isolate it and not retain impurities, and the syringe filter elution step of Isabel to effectively untrap and obtain the desired product. This would yield the predictable result of a method for preparing radiolabeled MAA particles purified via syringe filter.
As to claim 1, the 68Ga-MAA preparation protocol of Mathias teaches using a 68Ge/68Ga radiometal generator to produce a 68Ga radiometal generator eluate, combining the generator eluate with MAA particles from a commercially available labeling kit for 99mTc (Pulmolite®), and generating a final bulk solution of 68Ga-MAA in sterile saline (section 2, paragraphs 2 and 3). The selection of a vial as the vessel containing the final bulk solution would be routine optimization for a skilled artisan. Additionally, the syringe filter method of Mathias teaches the selective retention of 68Ga-MAA on a 0.2 µm nylon syringe filter (section 2, paragraph 3). Furthermore, spore recovery step of the protocol from Isabel teaches elution of material trapped on a syringe filter by passing phosphate buffered saline through the syringe filter in the direction opposite to the flow during the molecule loading step (pg. 1507, Spore Capture and Recovery Step).
As to claims 2-4, the radiolabeled MAA preparation protocol of Mathias teaches labeling the MAA particles with 68Ga (section 2, paragraph 3).
As to claims 5-7, the syringe filter method of Mathias teaches that using a 0.2 µm filter will selectively retain 68Ga-MAA (section 2, paragraph 3).
As to 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.
As to 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).
As to claim 11, the syringe filter taught by Isabel (pg. 1507, Spore Capture and Recovery Step) is considered disposable by the vendor, which a skilled artisan would recognize as describing the product as single-use.
As to 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).
As to claim 16, the syringe filter of Isabel comprises a Luer lock (pg. 1507, DARE Procedure).
Claims 12, 14, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Mathias in view of Isabel as applied to claims 1-11, 13, and 16 above, and further in view of Mueller (Mueller, D.; et. al., Appl. Radiat. Isot., 2017).
As described above, Mathias teaches a method of preparing 68Ga-MAA and a method of retaining 68Ga-MAA on a syringe filter (section 2, paragraphs 2 and 3) and Isabel teaches a method of eluting trapped material off single-use syringe filter cartridges (pg. 1507).
Mathias and Isabel do not teach preparing radiolabeled MAA particles in an automated process using an automated synthesizer and attaching the syringe to a single-use cassette in the automated process. Mathias and Isabel also do not teach pre-purifying the generator eluate on a cationic cartridge.
Mueller teaches an automated synthesis of 68Ga-labeled MAA (section 2.2) and the pre-purification of a generator eluate on a cation exchange cartridge (section 2.2).
A person of ordinary skill in the art would have recognized that applying the automated process of Mueller to the manual preparation of 68Ga-MAA of the combined teachings of Mathias and Isabel would enable fast and efficient preparation of 68Ga-MAA while limiting the radiation exposure of a person performing the claimed method. Furthermore, a person of ordinary skill in the art would have recognized that applying the cation exchange pre-purification of the 68Ga-containing generator eluate reduces the introduction of impurities from the generator elution step that may be introduced to the MAA labeling reaction.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to automate the 68Ga-MAA synthesis and purification process taught by Mathias in view of Isabel using a system like that described by Mueller and to further incorporate the cation exchange pre-purification of the generator eluate prior to the radiolabeling reaction. This would yield the predictable result of a fast, high-purity, high-yield automated method of preparing 68Ga-MAA that limits the operator’s exposure to radiation.
As to 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). 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 and purification.
As to 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).
As to 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).
Conclusion
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Eric P Mosher whose telephone number is (571)272-3258. The examiner can normally be reached Monday-Friday 9am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/E.P.M./Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612