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 .
Drawings
The following drawings are objected to: Fig 1A, 3A and B, 4, 5, 12A-D, and 13.
Figures 1A, 3B, 4, 5, 12A, 12B, 12C, 12D, and 13 are objected to because they are blurry and difficult to read. Fig 4 is objected to because the exploded view should be placed in brackets and labelled as a separate view. See MPEP 608.02; 37CFR 1.84(h)(1). Fig 3A (steps 1-9), Fig 3B (steps 1-6), and Fig 4 (all reference characters) are objected to as the reference characters are not mentioned in the description. See 37 CFR 1.84(p)(5).
Furthermore, Fig 5 and Fig 12A-D are objected to as color drawings. Appropriate correction is required.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Interpretations
Claim 2 recites a composition comprising < 6 µg of Lu-PSMA I&T. The examiner notes that open ended numerical ranges normally include 0 µg. However, the examiner notes that the claim is clearly directed to a radiopharmaceutical composition which requires lutetium. Therefore, the examiner interprets “< 6 µg” as imposing an upper limit on the quantity of lutetium without specifying a minimum; and, therefore, does not warrant inclusion of 0 µg of lutetium. See MPEP 2173.05(c)(II).
Claim 8 recites specific amounts and concentrations for the enumerated components of a radiopharmaceutical composition. According to the claim language, the examiner interprets these amounts and concentrations to refer to the amounts and concentrations in the radiopharmaceutical composition and do not refer to the amounts and concentrations used in a method of making the radiopharmaceutical composition. All examination reliant on this claim will be done according to this interpretation.
Claim 40 recites a radioactive content from about 70-130%. The examiner notes that the claim as written is silent as to what the radioactive content refers to. The examiner acknowledges that radioactive content could refer to the radioactive dose, radioactive concentration, the lutetium-177 concentration, the 177Lu-PSMA I&T concentration, the label on the storage vials, the content of radioactivity measured in radioactive concentration units or as absolute whole system activity. The examiner found examples of “radioactive content” in the specification in paragraphs [0092], [0093], [00232], [00522], and [00532]. Each reference to radioactive content was helpful in giving context to the range for radioactive content, but paragraph [00232] described the radioactive content as an acceptance criterion for the radioactivity in the formulation as a value concerned on a label. Therefore, for the purposes of examination, the examiner will interpret “radioactive content” to refer to stated value at the date of labelling. The date of labelling is presumed to be before the 90 hours after formulation described in claims and abstract of the instant application. The value of the radioactive content is interpreted to be the concentration of the 177Lu-PSMA I&T. The examiner interprets the range of 70% to 130% to modify an amount from within the 177Lu-PSMA I&T range of 5-15 µg/mL recited in claim 37.
Claim 41 recites a whole-body effective dose of about 3.3 Gy/GBq after administration in a subject in need thereof. The examiner interprets the subject in need thereof to refer to someone with some form of cancer that the treatment may address. Therefore, the whole-body effective dose does not read on healthy subjects. For the purposes of prior art, any art that describes mean whole-body effective doses for a subject with cancer will be permitted.
Claim Rejections - 35 USC § 112(a) – Written Description
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.
Claim 41 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 claim(s) 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.
Claim 41 recites a whole-body effective dose of about 3.3 Gy/GBq.
However, the instant specification does not offer sufficient description of the common structural elements or identifying characteristics that constitute this whole-body effective dose. While the claim defines the invention in functional language specifying a desired result, the disclosure also fails to sufficiently identify how the function is performed or the result is achieved. The instant disclosure provides information on a whole-body effective dose in a range of 0.01-0.5 Gy/GBq as of Fig 12D, paragraph [00186]. However, the instant specification is silent as to support for a whole-body effective dose of about 3.3 Gy/GBq. This claimed whole-body effective dose is unsupported by the written description. Applicant has not pointed out where the new claim is supported, nor does there appear to be a written description of the claim limitation ‘about 3.3 Gy/GBq’ in the application as filed. See MPEP 2163.03(V). Therefore, the instant specification does not provide a disclosure of corresponding structure in sufficient detail to demonstrate to one of ordinary skill in the art that the inventor possessed the invention including which features that the inventor considered to constitute a radiopharmaceutical composition which allow for the whole-body effective dose of about 3.3 Gy/GBq, as recited in the instant claims.
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.
Claims 2, 8-11, 36-39, 44 and 45 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 2 recites the limitation "Lu-PSMA I&T" in the second line of the claim. There is insufficient antecedent basis for this limitation in the claim because claim 1, from which claim 2 depends, recites "177Lu-PSMA I&T".
Claims 8recites the limitation 20% L-ascorbic acid but omits: units. 20% L-ascorbic acid is indefinite since the units are not listed, while 20% may refer to ratio of L-ascorbic acid to D-ascorbic acid, purity, w/v, or w/w. Claims 9-11 are rejected as indefinite since they are dependent on claim 8. The examiner will use the “w/v” interpretation for the purposes of prior art search.
Claim 9 recites the limitation "the ascorbic acid" in the first line of the claim. There is insufficient antecedent basis for this limitation in the claim because claim 8, from which claim 9 depends, recites "L-ascorbic acid".
The term “low” in claims 36, 37, and 45 is a relative term which renders the claims indefinite. The term “low” 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. Accordingly, the levels of hematotoxic and nephrotoxic toxicity in each claim is rendered indefinite by the use of the term “low” without adequate definition of that term in the claim or specifications. Further, claims 38, 39, 40, 41, and 44 are rejected as indefinite since they are dependent on claim 37.
Claim Rejections - 35 USC § 112(d)
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.
Claim 39 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.
Claim 39 recites concentrations of ascorbic acid from about 10 mg/mL to about 80 mg/mL. Claim 39 depends on claim 37 which recites "…(b) ascorbic acid in a concentration from about 10 mg/ml to about 50 mg/ml…" Claim 39 does not further limit the ascorbic acid concentration but expands it beyond the limitations of claim 37. Therefore, claim 39 is rejected as having improper dependence on claim 37.
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.
Claim(s) 1-2, 5-10, 35, 37-40, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over McCann et al. (US 11,129,912 B1).
McCann et al. (hereafter referred to as McCann) is drawn to 177Lu-PSMA I&T radiopharmaceuticals as of title, abstract, specs, and claims. McCann teaches a 177Lu-PSMA I&T radiopharmaceutical in high purity possesses extended shelf life and teaches various synthetic methods, compositions, and treatments comprising 177Lu-PSMA I&T from the abstract on page 1.
As to claim 1, McCann teaches a pH range that overlaps with the claimed range at pH 4.5. In such cases, even a slight overlap of ranges establishes a prima facie case of obviousness. See MPEP 2144.05(I). With respect to pH of the composition, the examiner notes that the pH range of 4.5-7.0 taught by McCann overlaps with the claimed pH range of 3.5-4.5.
In the alternative to claim 1, generally differences in concentration (e.g. pH of the composition) between the claimed invention and prior art will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. See MPEP 2144(II)(A). Additionally, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A). It would not have been inventive for the skilled artisan to have discovered the optimum or workable pH range and concentration of these components via routine experimentation.
As to claim 2, McCann teaches embodiment wherein 177Lu-PSMA I&T is provided in a concentration of 10 µg/mL. which is similar to the claimed concentration. See MPEP 2144.05(I) - re: ranges that do not overlap. In such cases, even similar ranges establish a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 5, McCann teaches radiopharmaceutical compositions without ethanol as of Example 2, col 29, lines 19-61.
As to claim 6, McCann teaches a radioactivity with a range from at least 100 MBq/mL to at least 1000 MBq/mL as of Col 22, lines 21-24. The claimed “radioactivity of about 0.5 GBq/mL” is about 500 MBq/mL which falls within the prior art range. The claimed radioactivity range lies inside the prior art radioactivity range in McCann as of Col 22, lines 21-24. In such instances where the claimed range lies inside a prior art range, it establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 7, McCann teaches one or more ascorbate compounds, which was defined to include ascorbic acid (Col 19, line38-40), in ranges from 5-120 mg/mL. The claimed “about 21 mg/mL to about 42.5 mg/mL ascorbic acid” falls within this range. The claimed ascorbate concentration range lies inside the prior art ascorbate concentration range. In such instances where the claimed range lies inside a prior art range, it establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 8, McCann teaches a radiopharmaceutical composition comprising the required components: 177Lu, PSMA I&T precursor, sodium acetate, hydrochloric acid, L-ascorbic acid, and specific activity less than or equal to 61 GBq in 6-8 mL of solution.
Regarding the lutetium-177 of claim 8, McCann teaches lutetium-177 as of Col 29, lines 38-40. The non-specified claimed range of 177Lu enables values which overlap with the range taught by McCann. The claimed lutetium-177 range lies inside the prior art lutetium-177. In such instances where the claimed range lies inside a prior art range, it establishes a prima facie case of obviousness. See MPEP 2144.05(I).
Regarding the PSMA-I&T precursor of claim 8, McCann teaches approximately 424 µg/mL concentration range as of Col 29, lines 30-34. The claimed range is similar to the prior art range of 463 µg/mL. Generally, differences in concentration (e.g. precursor concentration) between the claimed invention and prior art will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. See MPEP 2144(II)(A). Additionally, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A). It would not have been inventive for the skilled artisan to have discovered the optimum or workable pH range and concentration of these components via routine experimentation.
Regarding the 4 mL 0.4 M sodium acetate of claim 8, McCann teaches an acetate solution may be used as a buffer for 177Lu-containing compositions as of col 11, lines 14-21 and the use of a 0.4 M acetate solution for 177Lu-containing compositions as of col 26, lines 56-57. McCann does not teach the volume of the acetate solution in the composition. Generally, differences in concentration or temperature between the claimed invention and prior art will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. See MPEP 2144(II)(A). Additionally, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A). It would not have been inventive for the skilled artisan to have discovered the optimum or workable volume and concentration of these components via routine experimentation. Additionally, McCann teaches that the prior art may be scaled from a unit dose to a bulk solution as of col 23, lines 35-39. Mere scaling up of a prior art process capable of being scaled up, if such were the case, would not establish patentability in a claim to an old process so scaled. See MPEP 2144.04(IV)(A).
Regarding the 1.6 mL 0.05 M hydrochloric acid of claim 8, McCann teaches the use of a range from 0.05-0.4 N HCl as of col 29, lines 29 and 40. The claimed concentration of 0.05 M HCl falls within the prior art range of 0.05-0.4N HCl. The claimed hydrochloric acid concentration lies inside the prior art hydrochloric acid concentration. In such instances where the claimed range lies inside a prior art range, it establishes a prima facie case of obviousness. See MPEP 2144.05(I). Additionally, the volume of the HCl used is a result of the scale. McCann teaches the use of sodium acetate and a person having ordinary skill in the art would optimize accordingly to achieve an expected success with the concentration of sodium acetate. Mere scaling up of a prior art process capable of being scaled up, if such were the case, would not establish patentability in a claim to an old process so scaled. See MPEP 2144.04(IV)(A).
Regarding the about 150 µL 20% L-ascorbic acid in claim 8, McCann teaches L-ascorbic acid in a range of 99-247 mg/mL which is 9.9-24.5% w/v L-ascorbic acid as of col 26, lines 51-55. The claimed concentration falls within the prior art concentration range. The claimed L-ascorbic acid concentration range lies inside the prior art L-ascorbic acid range. In such instances where the claimed range lies inside a prior art range, it establishes a prima facie case of obviousness. See MPEP 2144.05(I). With respect to the volume, mere scaling up of a prior art process capable of being scaled up, if such were the case, would not establish patentability in a claim to an old process so scaled. See MPEP 2144.04(IV)(A).
Regarding the specific activity ≤ 61 GBq in 6-8 mL in claim 8, McCann teaches a specific activity of 100-1000 MBq/mL, which is 0.1-10 GBq/mL. The claimed volume range of 6-8mL creates an upper limit specific activity range of ≤ 7.6-10.2 GBq/mL. The less than or equal establishes everything below this range is also within the scope of the claim. The claimed specific activity lies inside the prior art specific activity. In such instances where the claimed range lies inside a prior art range, it establishes a prima facie case of obviousness. See MPEP 2144.05(I). With respect to the volume, mere scaling up of a prior art process capable of being scaled up, if such were the case, would not establish patentability in a claim to an old process so scaled. See MPEP 2144.04(IV)(A).
As discussed in detail above, McCann teaches radiopharmaceutical compositions comprising the required components: 177Lu, PSMA I&T precursor, sodium acetate, hydrochloric acid, L-ascorbic acid, and specific activity less than or equal to 61 GBq in 6-8 mL of solution. Therefore, the combined teachings of McCann render claim 8 prima facie obvious as combining prior art elements according to known methods would yield predictable results (MPEP 2143(i)(a)). A person of ordinary skill in the art would be motivated to combine McCann’s teachings as McCann teaches compositions comprising the required components are known in the art.
As to claim 9, McCann teaches a pH range that overlaps with the claimed range at pH 4.5. In such cases, even a slight overlap of ranges establishes a prima facie case of obviousness. See MPEP 2144.05(I). With respect to pH of the composition, the examiner notes that the pH range of 4.5-7.0 taught by McCann overlaps with the claimed pH range of 3.5-4.5.
As to claim 10, McCann teaches a pH range that overlaps with the claimed range at pH 4.5. In such cases, even a slight overlap of ranges establishes a prima facie case of obviousness. See MPEP 2144.05(I). With respect to pH of the composition, the examiner notes that the pH range of 4.5-7.0 taught by McCann overlaps with the claimed pH range of 3.5-4.5.
As to claim 35, McCann teaches the general conditions of a radiopharmaceutical composition comprising 177Lu-PSMA I&T, ascorbic acid in solution suitable for administration to a human patient at least 48 hours after formulation as of McCann col 30, lines 19-53. As such, it would not have been inventive for the skilled artisan to have discovered the optimum or workable range and concentration of these components via routine experimentation. McCann teaches a pH range that overlaps with the claimed range at pH 4.5. In such cases, even a slight overlap of ranges establishes a prima facie case of obviousness. See MPEP 2144.05(I). With respect to pH of the composition, the examiner notes that the pH range of 4.5-7.0 taught by McCann overlaps with the claimed pH range of 3.5-4.5.
As to claim 37, McCann teaches 177Lu-PSMA I&T in a concentration from 10-500 µg/mL as of col 23, lines 12-14. The concentration range with the range taught by McCann. In such cases, even a little overlap of ranges establishes a prima facie case of obviousness. See MPEP 2144.05(I). With respect to concentration of the 177Lu-PSMA I&T, the examiner notes that the concentration range of 10-500 µg/mL taught by McCann overlaps the claimed concentration range of about 5-15 µg/mL.
Regarding the ascorbic acid in claim 37, the ascorbic acid in a concentration range from about 10-50 mg/mL is taught by McCann. McCann teaches one or more ascorbate compounds, which was defined to include ascorbic acid (Col 19, line38-40), in ranges from 5-120 mg/mL. The claimed “about 10 mg/mL to about 50 mg/mL ascorbic acid” falls within this range. The claimed ascorbic acid concentration range lies inside the prior art ascorbic acid concentration range. In such instances where the claimed range lies inside a prior art range, it establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 38, McCann teaches a radiopharmaceutical composition with a radioactivity from 100-1,000 MBq/mL as of col 9, lines 56-63. This lies within claimed range of less than 300 mCi which is less than 11,100 MBq. Since the prior art range lies fully within the range claimed, the claimed range is anticipated by McCann and claim 38 with all the limitations of claim 37 is rendered obvious to a person having ordinary skill in the art.
As to claim 39, the claimed ascorbic acid concentration range is 10-80 mg/mL. McCann teaches one or more ascorbate compounds, which was defined to include ascorbic acid (Col 19, line38-40), in ranges from 5-120 mg/mL. The claimed about 10-80 mg/mL ascorbic acid falls within this range. The claimed ascorbic acid concentration range lies inside the prior art ascorbic acid concentration range. In such instances where the claimed range lies inside a prior art range, it establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 40, the claimed 70-130% of an amount of radioactive content, interpreted by the examiner to mean 70-130% of a value within the range of about 5-15 µg/mL of 177Lu-PSMA I&T after formulation, gives a possible range from 3.5-19.5 µg/mL of 177Lu-PSMA I&T in solution after formulation. McCann teaches 177Lu-PSMA I&T in a concentration from 10-500 µg/mL as of col 23, lines 12-14. The concentration range with the range taught by McCann. In such cases, even a little overlap of ranges establishes a prima facie case of obviousness. See MPEP 2144.05(I). With respect to concentration of the 177Lu-PSMA I&T, the examiner notes that the concentration range of 10-500 µg/mL taught by McCann overlaps the possible claimed concentration range of 3.5-19.5 µg/mL.
As to claim 44, McCann teaches a radiochemical purity of at least 97% in a range from 3, 4, and 5 days after preparation as of col 20, lines 5-10. While the prior art time range lists times beyond 0 hours, the radiochemical purity decreases with time and so, in reverse, includes 0 hour. The claimed radiochemical purity range overlaps the prior art radiochemical purity range. In such instances where the claimed range lies inside a prior art range, it establishes a prima facie case of obviousness. See MPEP 2144.05(I).
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over McCann et al. (US 11,129,912 B1) in view of Okamoto et al. (J. Nucl. Med. 2017, 58, 445-450)
As to claim 41, McCann teaches the radiopharmaceutical claimed in 37 claimed in 41.
McCann does not teach the whole-body effective dose of 23 ± 20 Gy (3.3 Gy/GBq).
Okamoto et al. (hereafter referred to as Okamoto) teaches a dosimetry for all lesions to receive a mean dose per cycle of 23 ± 20 Gy (3.3 Gy/GBq) as of Okamoto, pg 3, section Dosimetry for Tumor Lesions, sentence 1. Given that McCann and Okamoto are drawn to the same composition, a person having ordinary skill in the art would be motivated to combine the teaching in McCann with the teaching of Okamoto to get a composition with predictable success at achieving a similar whole-body effect dose as claimed rendering claim 41 prima facie obvious. See MPEP 2144.05(I)
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over McCann et al. (US 11,129,912 B1) in view of Banerjee et al. (Chem. Rev. 2015, 115, 2934-2974).
As to claim 3, McCann teaches a diethylentriaminepentaacetic acid (DTPA) chelator for 177Lu-PSMA I&T.
McCann does not teach ethylenediaminetetraacetic acid (EDTA).
Banerjee et al. (hereafter referred to as Banerjee) teaches common chelating agents, including EDTA, used for 177Lu radiopharmaceuticals as of Fig 4.
Alternatively as to the chelator, while McCann does not disclose the same chelator, the function of McCann chelator and the claimed chelator serve the same purpose: in such instances swapping similar features that serve the same purpose establishes a prima facie case of obviousness. See MPEP 2143(I)(B). With regard to the chelator, McCann teaches the use of a sequestering agent suitable to remove uncomplexed lutetium-177, such as diethylentriaminepentaacetic acid (DTPA) as of Col 23, lines 10-14. This sequestering agent is a chelator which can have the same function as EDTA as stated by claimed art specifications paragraph [0077], [00124], [00125], and [00130]. A simple substitution of one known element for another would have led a person of ordinary skill in the art to obtain predictable results. The prior art contained DPTA with the general conditions of claim 1, the substituted EDTA is a stated substitute as cited above. So, one of ordinary skill in the art could have substituted EDTA for DTPA and the results of the substitution would have been predictable.
Further as to claim 3, the concentration range of EDTA lies inside ranges disclosed by the prior art as of the concentration range of DTPA in McCann as of Col 23, lines 10-14. In such instance where the claimed range lies inside a prior art range, it establishes a prima facie case of obviousness. See MPEP 2144.05(I). With regard to the concentration of the chelator, the examiner notes that the 0.01 to 0.50 mg/mL (which is 10-50 µg/mL) taught by McCann contains the claimed range of 13-18 µg/mL.
Claims 4, 11, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over McCann et al. (US 11,129,912 B1) in view of Erion et al. (WO 2008009444 A1).
Erion et al. (hereafter referred to as Erion) is drawn to use of ethanol to stabilize radio-labelled pharmaceutical compositions as of Erion, title and abstract.
As to claim 4, McCann teaches that ethanol may be used in radiopharmaceutical compositions as of col 22, lines 34-40. See the rejection of the radiopharmaceutical composition above. Further, McCann does not teach the amount of ethanol to be used in the radiopharmaceutical composition.
Erion teaches the use of ethanol “…in a quantity sufficient to prevent radiolysis…” to stabilize radiopharmaceutical compositions as of Erion’s claim 7. Erion further teaches a radiopharmaceutical composition containing 1-20% v/v as of page 6, line 15-17. “In general, the quantity of ethanol in the injection liquid, is 1 to 20 % v/v, preferably approx. 5 to 20% v/v. Generally, approx. 10% v/v of ethanol is sufficient for an adequate stabilization.”
The claimed “about 35 µL to about 40 µL ethanol per mL of solution” is equivalent to about 3.5-4% v/v in the solution. The claimed ethanol range lies within the prior art range. Therefore, it would have been prima facie obvious for one of ordinary skill in the art to have added ethanol in ranges used in Erion to the ascorbic acid in McCann to the radiopharmaceutical composition in order to have achieved predictable results (improved stability and shelf life such as the radiopharmaceutical composition of McCann) is prima facie obvious. See MPEP 2144.05(I).
As to claim 11, the result of adding ethanol in the ranges discussed in Erion to the radiopharmaceutical concentration of McCann rationale from claim 4 is also applicable here. The claimed ethanol amount of 0.75 mL to 6 to 8 mL of solution which has a range the overlaps with the range discussed in Erion. While the prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 45, McCann and Erion teach a radiopharmaceutical composition comprising the required components: 177Lu-PSMA I&T solution for injection, 177Lu-PSMA I&T (about 5-15 µg/mL), ascorbic acid (about 10-50 mg/mL), ethanol (about 1-10 % (v/v), a chelating agent (about 0.001-0.15 % (w/w) of the total weight of the radiopharmaceutical composition, and a solution pH (about 3-5)
Regarding the 177Lu-PSMA I&T in an amount from about 5-15 µg/mL in claim 45, McCann teaches Lu-PSMA I&T in a concentration from 10-500 µg/mL as of col 23, lines 12-14. The concentration range with the range taught by McCann. In such cases, even a little overlap of ranges establishes a prima facie case of obviousness. See MPEP 2144.05(I). With respect to concentration of the Lu-PSMA I&T, the examiner notes that the concentration range of 10-500 µg/mL taught by McCann is similar to the claimed concentration range of 5-15 µg/mL.
Regarding the ascorbic acid in a concentration from about 10-50 mg/mL in claim 45, McCann teaches one or more ascorbate compounds, which was defined to include ascorbic acid (Col 19, line38-40), in ranges from 5-120 mg/mL. The claimed “about 10 mg/mL to about 50 mg/mL ascorbic acid” falls within this range. The claimed ascorbic acid concentration range lies inside the prior art ascorbic acid concentration range. In such instances where the claimed range lies inside a prior art range, it establishes a prima facie case of obviousness. See MPEP 2144.05(I).
Regarding a chelating agent in an amount from about 0.001-0.15 % (w/w) of the total weight of the radiopharmaceutical composition in claim 45, McCann teaches this as of Col 23, lines 10-14. The claimed range of 0.001-0.15 % (w/w) overlaps with the prior art range of 0.01-0.50 mg/mL, which is roughly about 0.01-0.5 % (w/w). In such cases, overlap of ranges establish a prima facie case of obviousness. See MPEP 2144.05(I). With respect to the chelating agent concentration range, the examiner notes that the concentration range taught by McCann overlaps with the claimed concentration range.
Within claim 45, the radiopharmaceutical composition comprises ethanol in a concentration from about 1-10 % (v/v).
McCann does not teach a concentration range for ethanol in a radiopharmaceutical composition.
Erion teaches the use of ethanol for stabilizing radiopharmaceutical compositions in a concentration of 1-20% v/v as of page 6, line 15-17. The claimed range 1-10 % (v/v) lies within the prior art range. The claimed ethanol concentration range lies inside the prior art ethanol concentration range. In such instances where the claimed range lies inside a prior art range, it establishes a prima facie case of obviousness. See MPEP 2144.05(I).
Therefore, regarding claim 45, it would have been prima facie obvious for one of ordinary skill in the art to have added ethanol in ranges used in Erion to the ascorbic acid in McCann to the radiopharmaceutical composition in order to have achieved predictable results (improved stability and shelf life such as the radiopharmaceutical composition of McCann) is prima facie obvious. See MPEP 2144.05(I).
Claim 36 is rejected under 35 U.S.C. 103 as being unpatentable over McCann et al. (US 11,129,912 B1) in view of Erion et al. (WO 2008009444 A1) in further view of Vyas et al. (Vyas, M., Fagan, J., Lim, R., & Garett, N. (2020, October). Lutetium-177-PSMA I&T for progressing metastatic castrate-resistant prostate cancer: A single NZ centre experience. Paper presented at the New Zealand Society for Oncology-2020, Auckland, New Zealand).
As to claim 36, the examiner notes the claim has the following required components: 177Lu-PSMA I&T (enough for intended use), ascorbic acid (210-700 mg), ethanol (274-706 mg), and pH (about < 5).
Regarding the 177Lu-PSMA I&T in sufficient amounts of radioactivity for intended use in claim 36, McCann teaches a 177Lu-PSMA I&T solution for an intended use (e.g. injection)
Regarding the ascorbic acid (210-700 mg) in claim 36, McCann teaches ascorbic acid in concentrations around 162 mg/mL as of Example 2, col 29, lines 17-55. Concentration falls within the possible claimed concentration range of the ascorbic acid. Additionally, while the prior art does not teach ascorbic acid in terms of amount used but concentration used, the ranges overlap when 2 mL of the prior art solution is obtained. In such cases, overlapping or even similar ranges establish a prima facie case of obviousness. See MPEP 2144.05(I).
Regarding the ethanol (about 274-706 mg) in solution in claim 36, McCann teaches the use of ethanol in radiopharmaceutical compositions as of Col 22, lines 34-40.
McCann does not teach amounts of ethanol to be used in the radiopharmaceutical composition.
Erion is drawn to the use of ethanol for stabilizing radiopharmaceutical compositions, see rationale discussed above. Erion teaches a radiopharmaceutical composition containing 1-20% v/v as of page 6, line 15-17. “In general, the quantity of ethanol in the injection liquid, is 1 to 20 % v/v, preferably approx. 5 to 20% v/v. Generally, approx. 10% v/v of ethanol is sufficient for an adequate stabilization.” In the claimed ethanol amount of 274-706 mg, this range can be similar to the prior art range in a bulk solution for injection. If the bulk solution is 100 mL, then the claimed ethanol range lies within or similar to the prior art range. Therefore, it would have been prima facie obvious for one of ordinary skill in the art to have added ethanol in ranges used in Erion to the ascorbic acid in McCann to the radiopharmaceutical composition in order to have achieved predictable results. See MPEP 2144.05(I).
Regarding the pH of the solution that is about 5 or below in claim 36, McCann teaches a pH range of 4.5-7 (Col 26, lines 52-67) that overlaps with the claimed range of about 5 or below. In such cases, even a slight overlap of ranges establishes a prima facie case of obviousness. See MPEP 2144.05(I).
Regarding the low levels of hematotoxic and nephrotoxic toxicity in claim 36, the examiner notes this speaks to the intended use. Since the composition has the components and characteristics of the prior art, it has the properties as well. See MPEP 2112.01(III).
Regarding the prostate-specific antigen decline is more than about 50% in claim 36, the examiner notes that this speaks to intended use. Since the composition has the components and characteristics of the prior art, it has the properties as well. See MPEP 2112.01(III).
Alternatively to the contingent clause interpretation, McCann teaches the radiopharmaceutical composition of claim 36, McCann does not teach the PSA decline of more than about 50%.
Vyas et al. (hereafter referred to as Vyas) teaches 177Lu-PSMA I&T demonstrating prostate-specific antigen decline that is more than about 50% as of page 16. Therefore, it would have been obvious to a person having ordinary skill in the art at the time of invention to obtain a PSA decline that is more than about 50% for 177Lu-PSMA I&T.
Non-Statutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Co-pending Application No. 19/063,049
Claims 1-11, 35-41, and 44-45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 7, 23, 24, 25, and 29 of co-pending application No. 19/063,049 in view of McCann; Okamoto; Banerjee; Erion and Vyas.
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons:
Instant claims 1, 3, 5, 7, 10, and 35 are taught by conflicting claims in co-pending application No. 19/063,049 claims 1, 3, 5-7, 23 24, 25, and 29.
Instant claim 1 is drawn to a radiopharmaceutical composition comprising 177Lu-PSMA I&T, ascorbic acid at a pH of 3.5 to 3.5 in solution suitable for human use at least 90 hours after formulation and with a radiochemical purity of 95% or greater at administration.
Conflicting claim 1 teaches a 177Lu-PSMA I&T composition suitable for administration to a human, conflicting claim 3 teaches a radiochemical purity of 95% or greater to at least 120 hours after formulation, conflicting claims 23 and 24 teach ascorbic acid; and, conflicting claim 7 teaches a composition pH from 3.5-4.5.
Instant claim 3 is drawn to disodium EDTA concentration of 13-18 µg/mL.
Conflicting claim 25 teaches the use of DTPA which serves the same purpose as EDTA and would be used to make obvious the use of EDTA.
Instant claim 5 is drawn to no inclusion of ethanol.
Conflicting claims 1, 7, 24, and 29 demonstrate that ethanol does not need to be included.
Instant claim 7 is drawn to a composition with ascorbic acid with concentrations from about 21-42.5 mg/mL.
Conflicting claim 24 state the use of ascorbic acid at a concentration from at least 28 mg/mL. The ranges overlap and the two claims would be held obvious over each other.
Instant claim 10 is drawn to a solution with a pH of 3.5 to 4.5.
Conflicting claims 5-7 teach a solution pH in the range of 3.5-4.5.
Instant claim 35 is drawn to a radiopharmaceutical composition comprising 177Lu-PSMA I&T and ascorbic acid with a solution pH of 3.5-4.5 suitable for injection and suitable for administration more than 48 hours after formulation.
Conflicting claim 1 teaches a 177Lu-PSMA I&T composition suitable for administration to a human, conflicting claim 3 teaches a radiochemical purity of 95% or greater to at least 120 hours after formulation, conflicting claims 23 and 24 teach ascorbic acid; and, conflicting claim 7 teaches a composition pH from 3.5-4.5.
However, the claims of 19/063,049 do not expressly teach the claim 2 amount of 177Lu-PSMA I&T, ethanol amounts in claims 4, 11, 36, 37, and 45, the radioactivity of claim 6, the amounts materials used to make a radiopharmaceutical composition in claim 8, nor the ascorbic acid concentration in claim 9 for that composition of claim 8.
As noted in the current rejections above, the combined teachings of McCann render obvious claims 1-2, 5-10, 35, 37-40, and 44. The combined teachings of McCann and Okamoto render obvious claim 41. The combined teachings of McCann and Banerjee render obvious claim 3. The combined teachings of McCann and Erion render obvious claims 4, 11 and 45. The combined teachings of McCann, Erion and Vyas render obvious claim 36.
As claims 1, 3, 7, 23, 24, 25, and 29 of co-pending application No. 19/063,049 and the teachings of McCann, Okamoto, Banerjee , Erion, and Vyas all teach radiopharmaceutical compositions, it would have been obvious to combine the claims 1, 3, 7, 23, 24, 25, and 29 of co-pending application No. 19/063,049 with McCann, Okamoto, Banerjee, Erion and Vyas because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of the claimed radiopharmaceutical composition.
Co-Pending Application No. 18/791,300
Claims 1-11, 35-41, and 44-45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5-7, 20-22, and 30 of copending application No. 18/791,300 in view of McCann; Okamoto; Banerjee; Erion and Vyas.
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons:
Instant claims 1, 3, 5, 7, 10, and 35 are taught by conflicting claims in co-pending application No. 18/791,300 claims 1, 3, 5-7, 20-22, and 30.
Instant claim 1 is drawn to a radiopharmaceutical composition comprising 177Lu-PSMA I&T, ascorbic acid at a pH of 3.5 to 4.5 in solution suitable for human use at least 90 hours after formulation and with a radiochemical purity of 95% or greater at administration.
Conflicting claim 1 teaches 177Lu-PSMA I&T suitable for administration to humans, conflicting claims 20 and 21 teach ascorbic acid, conflicting claims 4-7 teach a pH range including 3.5-4.5, conflicting claim 3 teaches administration to a human patient in need thereof for at least 90 hours after formulation, and conflicting claims 27 and 30 teach a composition with a radiochemical purity of 95% or greater.
Instant claim 3 is drawn to 13-18 µg/mL of EDTA for the radiopharmaceutical composition.
Conflicting claim 22 teaches the use of DTPA, a chelator for the same purpose. The specifications further show that DTPA and EDTA may be used in alternative form.
Instant claim 7 is drawn to 21-42.5 mg/mL ascorbic acid for the radiopharmaceutical composition.
Conflicting claim 20 teaches 10-50 mg/mL ascorbic acid. The instant claim range lies fully within the conflicting claim 20 range.
Instant claim 10 is drawn to a solution pH from 3.5 to 4.5.
Conflicting claim 5-7 and 30 teach a solution pH including a range of 3.5 to 4.5.
Instant claim 35 is drawn to a 177Lu-PSMA I&T solution for injection with a pH of 3.5-4.5 and suitable for administration more than 48 hours after formulation.
Conflicting claim 1 teaches 177Lu-PSMA I&T suitable for administration, conflicting claims 20 and 21 teach ascorbic acid, conflicting claims 4-7 teach a pH range including 3.5-4.5, conflicting claim 3 teaches administration in need thereof for at least 48 hours after formulation.
Regarding instant claims 2, 6, 8, 9, 37, 38, 39, 40, and 44, co-pending application 18/791,300 teaches the radiopharmaceutical composition as discussed above.
However, the conflicting patent application does not expressly teach the limitations of instant claims 2, 6, 8, 9, 37, 38, 39, 40, and 44.
As noted in the current rejections above, the combined teachings of McCann render obvious claims 1-2, 5-10, 35, 37-40, and 44. The combined teachings of McCann and Okamoto render obvious claim 41. The combined teachings of McCann and Banerjee render obvious claim 3. The combined teachings of McCann and Erion render obvious claims 4, 11 and 45. The combined teachings of McCann, Erion and Vyas render obvious claim 36.
As claims 1, 3, 5-7, 20-22, and 30 of copending application No. 18/791,300 and the teachings of McCann, Okamoto, Banerjee , Erion, and Vyas all teach radiopharmaceutical compositions, it would have been obvious to combine the claims 1, 3, 5-7, 20-22, and 30 of copending application No. 18/791,300 with McCann, Okamoto, Banerjee, Erion and Vyas because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of the claimed radiopharmaceutical composition.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Evan M Lewoczko whose telephone number is (571)272-9830. The examiner can normally be reached Monday-Friday 9-5PM.
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/EVAN M LEWOCZKO/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612