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 . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 112 – New Matter
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.
Claims 41-60 are 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 “about 100 pg to about 3000 pg of elemental copper.”
Claim 46 recites “1450 pg” twice or once per day, based on age.
Claims 48 and 52 recite the unit “pg”.
The originally filed disclosure does not appear to provide support for about “100 pg to about 3000 pg”; or, for about “1450 pg”. The originally filed disclosure does not appear to support units in picograms (pg), as recited by the claims.
The originally filed disclosure states elemental copper provided in amounts equivalent to about 100 μg to 3000 μg elemental copper [0015], where the units are in microgram, rather than picogram, as instantly recited. The originally filed disclosure states [0018] 1450 µg administered once or twice, based on age. Paragraph [0018] of the originally filed disclosure states units of microgram, rather than picogram, as is instantly claimed.
In the interest of compact prosecution, the Examiner is interpreting claims 41, 46, 48 and 52 as reciting micrograms; however, amendment, and/or clarification, of the claim scope is required. The Examiner recommends amendment of the claims, from pg, to μg.
Claim Rejections - 35 USC § 112 –
Indefiniteness and Lack of Antecedent Basis
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 53 and 56 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 53 does not recite dependency. Appropriate correction is required.
Claim 56 recites the limitation "the instructions" in line one. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 103 - Obviousness
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 33-42 and 44-46 and 55-57 are rejected under 35 U.S.C. 103 as being unpatentable over Kaler et al (US 2018/0312871 A1).
Kaler taught methods of treating copper disorders, including Menkes disease, [abstract] comprising administering to subjects, by subcutaneous injection, copper histidinate. The copper histidinate was administered at from about 50 µg to about 1000 µg, or about 500 µg [0082], administered as a single dose, multiple doses (e.g., 2, 3, 4, or more doses), or additional doses (e.g., 3 doses of 1000 µg reads on the instant claim 44 recitation of 3 mg) [0072, 0082-0083].
Claim 33 is rendered prima facie obvious over the teachings of Kaler, because it is prima facie obvious to combine prior art elements according to known methods, in order to yield predictable results. In the instant case, all the claimed elements (e.g., subcutaneous administration of copper histidinate) were known in the prior art (e.g., Kaler) and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would yield nothing more than predictable results (e.g., a method of treating cooper disorders, including Menkes disease) to one of ordinary skill in the art. MPEP 2143.A.
Further regarding claim 33, the instant claim 33 recites “administering copper histidinate via a subcutaneous route… thereby increasing serum copper histidinate levels in the subject”.
Regarding claim 57, the instant claim 57 recites a peak detectable level of copper histidinate in the serum at about ½ hour to 1 hour following administration.
Kaler taught 3 mg copper histidinate, as discussed above, which is 500 µg elemental copper (see the below calculation).
The originally filed disclosure [0018] states that when administering copper histidinate via a subcutaneous route at a dosage of 500 µg elemental copper, the copper peaks in the serum at about ½ hour to 1 hour following administration, thereby increasing serum copper histidinate levels in the subject [see also ¶s 0105 and 0111].
It appears that the methods of the instant claims (e.g., subcutaneous administration of 500 µg elemental copper, via copper histidinate) and those of the prior art (e.g., subcutaneous administration of 500 µg of elemental copper, via copper histidinate) would reasonably be expected to yield substantially the same physical and chemical properties (e.g., increasing serum copper, and with a peak detectable level of copper histidinate at about ½ to 1 hour following subcutaneous administration of copper histidinate).
Inherent features need not be recognized at the time of the invention. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. MPEP 2112 II. It should be noted that a chemical composition (500 µg elemental copper, via 3 mg copper histidinate) and its properties (increasing serum copper, and with a peak detectable level of copper histidinate at about ½ to 1 hour following subcutaneous administration of 500 µg elemental copper, via 3 mg copper histidinate) are inseparable. If the prior art teaches the identical chemical compounds and methods, then the properties that the Applicant discloses and/or claims are necessarily present.
The Examiner notes that 500 µg elemental copper is equivalent to 2925.7 µg of copper histidinate, as per the following calculation:
The molecular formula for copper histidinate is C12H16CuN6O4, and its molecular weight is approximately 371.84 grams per mole (g/mol).
The atomic weight (molar mass) of elemental copper (Cu) is approximately 63.55 g/mol.
The ratio of the masses is: (Molar mass of Copper Histidinate) ÷ (Molar mass of elemental Cu) = (371.84 g/mol) ÷ (63.55 g/mol) ≈ 5.85, so 5.85 times the mass of copper histidinate is needed to get the same amount of elemental copper.
For 500 µg of elemental copper:
500 µg elemental Cu x 5.85 ≈ 2,925 µg Copper Histidinate
Regarding claims 58-60, the instant claim 58 recites a copper histidinate distribution phase half-life of about 2-3 hours.
The instant claim 59 recites a copper histidinate terminal elimination phase half-life at about 30-150 hours.
The instant claim 60 recites a copper histidinate terminal elimination phase half-life at about 75 hours.
As previously discussed, Kaler taught 3 mg copper histidinate, which is 500 µg elemental copper
The originally filed disclosure [0018] states that when administering copper histidinate via a subcutaneous route at a dosage of 500 µg elemental copper, the copper histidinate distribution phase half-life is about 2-3 hours; the terminal elimination phase half-life t ½ is at about 30-150 hours; and, the terminal elimination phase half-life (t ½) is about 75 hours.
As previously discussed, it appears that the methods of the instant claims (e.g., subcutaneous administration of 500 µg elemental copper, via 3 mg copper histidinate) and those of the prior art (e.g., subcutaneous administration of 500 µg elemental copper, via 3 mg copper histidinate) would reasonably be expected to yield substantially the same physical and chemical properties (e.g., copper histidinate distribution phase half-life at about 2-3 hours; the terminal elimination phase half-life (t ½ )at about 30-150 hours; and, the terminal elimination phase half-life (t ½) at about 75 hours).
Inherent features need not be recognized at the time of the invention, as discussed above. It should be noted that a chemical composition (500 µg elemental copper administered subcutaneously) and its properties (copper histidinate distribution phase half-life at about 2-3 hours; the terminal elimination phase half-life (t ½) at about 30-150 hours; and, the terminal elimination phase half-life (t ½) at about 75 hours) are inseparable.
Kaler reads on claims 33, 40 and 57-60.
The instant claim 41 recites about 100 µg to about 3000 µg elemental copper.
Kaler taught copper histidinate at 1000 µg, as previously discussed.
The Examiner notes that 1000 µg copper histidinate is equivalent to 170.9 µg of elemental copper, as per the following calculation:
One thousand micrograms (𝜇g) of copper histidinate contains approximately 170.9 micrograms (𝜇g) of elemental copper.
This calculation is based on the molecular weights of copper histidinate and elemental copper.
The molecular formula for copper histidinate is C12H16CuN6O4, and its molecular weight is approximately 371.84 grams per mole (g/mol).
The atomic weight (molar mass) of elemental copper (Cu) is approximately 63.55 g/mol.
The percentage of elemental copper in copper histidinate is calculated as:
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(Molar mass of Cu) ÷ (Molar mass of Copper Histidinate) × 100 % = (63.55 g/mol) ÷ (371.84 g/mol) × 100% ≈ 17.09% elemental copper.
Therefore, for a 1000 𝜇g sample of copper histidinate:1000 𝜇g × 0.1709 ≈ 170.9 𝜇g of elemental copper
Copper histidinate | copper supplement | CAS#13870-80-9
Theoretical Analysis * MedKoo Cat#: 128479. * Name: Copper histidinate. * CAS#: 13870-80-9. * Chemical Formula: C12H16CuN6O4. * Ex...
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MedKoo Biosciences
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Copper bis(histidinate) | C12H16CuN6O4 | CID 151722
3 Chemical and Physical Properties * 3.1 Computed Properties. Property Name. 371.84 g/mol. Computed by PubChem 2.2 (PubChem releas...
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National Institutes of Health (NIH) | (.gov)
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[FREE] Question: What is the molar mass of copper (Cu)? ... - Brainly
Feb 7, 2023 — An atom of copper has an atomic mass of 63.546 amu. So, the molar mass of copper metal is equals to the 63.546 g/mol. M...
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The instant claim 41 recites elemental copper equivalent of about 100 µg to about 3000 µg.
Kaler taught 170.9 𝜇g of elemental copper.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. MPEP 2144.05 A.
The instant claim 42 recites “copper histidinate administered in an amount equivalent to 0.5 mg elemental copper”.
Kaler taught copper histidinate at from about 50 µg to about 1000 µg, as previously discussed, administered as a single dose, multiple doses (e.g., 2, 3, 4, or more doses), or additional doses (e.g., 3 doses of 1000 µg reads on 3 mg, as discussed) [0072, 0082-0083].
The Examiner notes that approximately 2926 µg of copper histidinate is equivalent to 0.5 mg, or 500 µg of elemental copper, as previously discussed.
The instant claim 42 recites an equivalent of 0.5 mg elemental copper, which is 2926 µg, as taught by Kaler and as previously discussed. A prima facie case of obviousness exists because of overlap, as discussed above.
Claims 44-46 are rendered prima facie obvious because Kaler taught administration as a single dose, multiple doses (e.g., 2, 3, 4, or more doses), or additional doses, from about 50 µg to about 1000 µg (e.g., 3 doses of 1000 µg reads on 3 mg, as discussed) [0072, 0082-0083]. Daily administration of multiple doses was taught at claims 32-33. Administration, based upon a subjects age, of less than or greater than 12 months of age, was taught [0082].
Claim 44 recites about 3.0 mg per day.
Claim 45 recites about 3.0 mg per day as a single or twice daily injection.
Claim 46 recites about 1450 µg once or twice daily, depending on if the subject is greater than or less than 12 months of age.
Kaler taught from about 50 µg to about 1000 µg, administered as a single dose, multiple doses (e.g., 2, 3, 4, or more doses), or additional doses. A prima facie case of obviousness exists because of overlap, as discussed above.
Claim 55 is rendered prima facie obvious because Kaler taught ATP7A-Related Distal Motor Neuropathy (e.g., reads on a missense mutation) [0030-0031, 0035, 0076, 0084-0085].
Claim 56 is rendered prima facie obvious because Kaler taught that one of ordinary skill in the art can identify a subject as having an ATP7A-related copper transport disorder based on clinical presentation, serum copper levels (e.g., Menkes disease), and/or genetic diagnosis (e.g., presence of one or more mutations in the gene encoding ATP7A). (e.g., reads on instructions including performing a genetic test to identify an ATP7A mutation) [0076].
Claim 43 is rejected under 35 U.S.C. 103 as being unpatentable over Kaler et al (US 2018/0312871 A1), in view of Tchan et al (JIMD Reports, 2012, 81-84).
The 35 U.S.C. 103 rejection over Kaler was previously discussed. As discussed, Kaler taught copper histidinate at from about 50 µg to about 1000 µg, administered as a single dose, multiple doses (e.g., 2, 3, 4, or more doses), or additional doses.
Kaler was not specific, though, a single dose of about 3.0 mg, as recited in claim 43.
Tchan taught, in the treatment of Menkes disease [title], copper-histidinate injections administered at 3 mg [page 82, right column, 3rd paragraph], where the patient tolerated copper-histidinate injections, with improvement, no long-term complications and with a good quality of life [page 83, last paragraph].
It would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Kaler, a 3 mg dosage, as taught by Tchan. The ordinarily skilled artisan would have been motivated to treat Menkes disease, with improvement, no long-term complications and with a good quality of life by the patient, as taught by Tchan [page 83, last paragraph].
Regarding the amount of copper histidinate, the differences in the claimed subject matter and the prior art are 50 µg to about 1000 µg, as taught by Kaler, versus 3.0 mg, as instantly claimed.
Kaler is not silent as the amount of the copper histidinate. For example, Kaler taught copper histidinate at 50 µg to about 1000 µg. However, Kaler was not specific the claimed 3.0 mg in a single dose. Nevertheless, Tchan taught that copper histidinate is useful at 3.0 mg, an amount as instantly recited. Copper histidinate, and its amount, is recognized to have different effects (greater or less improvement in the treatment of Menkes disease, as taught at the title and final paragraph of Tchan) with changing amounts used. Thus, the general condition (the concentration) is known, and the amount of copper histidinate is recognized to be result effective. As such, result effective variables can be optimized by routine experimentation, and it would have been prima facie obvious to optimize Kaler’s amount of copper histidinate, as taught by Tchan et al. See MPEP 2144.05.
With the combined teachings of Kaler and Tchan, the ordinarily skilled artisan would have had a reasonable expectation of success, without undue experimentation, in arriving at the claimed amount of copper histidinate.
Claims 47 and 53-54 are rejected under 35 U.S.C. 103 as being unpatentable over Kaler et al (US 2018/0312871 A1), in view of the US Health and Human Services (WO 2010/042102 A1) (hereafter, US HHS).
The 35 U.S.C. 103 rejection over Kaler was previously described.
Although Kaler taught subcutaneous injections, Kaler was silent a vial comprising a lyophilized formulation, as recited in claim 47. Kaler was silent stability, as recited in claims 53-54.
The US HHS taught the preparation, and administration to subjects, of copper histidine, for use in treating individuals diagnosed with Menkes disease. The formulation of copper histidinate was aliquoted into vials, and freeze-dried, for convenient administration [page 25, line 8]. Vials were stoppered under vacuum and stored at -20°C until use. For injection, the contents of the vial were reconstituted with 0.9% Sodium Chloride Injection, USP. When reconstituted, each mL contained copper histidine equivalent to 500 μg copper (II) as a clear solution (e.g., reads on stable formulation) [Example 2; see also page 25, lines 8-12].
It would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Kaler, a vial comprising a lyophilized formulation, as taught by the US HHS. The ordinarily skilled artisan would have been motivated to include a formulation for convenient administration, as taught by the US HHS at Example 2, and at lines 8-12 of page 25.
Regarding claims 53-54, although the US HHS taught a clear solution upon reconstitution, the US HHS was not specific stability, at the times or temperatures, as recited. Nevertheless, it would be prima facie obvious to one of ordinary skill in the art to manufacture a formulation with stability throughout various times and temperatures. The ordinarily skilled artisan would be motivated by the US HHS’ guidance to prepare copper histidinate for convenient administration, as previously discussed.
Claims 48-52 are rejected under 35 U.S.C. 103 as being unpatentable over Kaler et al (US 2018/0312871 A1), in view of US Health and Human Services (WO 2010/042102 A1) (hereafter, US HHS) and further in view of Tchan et al (JIMD Reports, 2012, 81-84).
The 35 U.S.C. 103 rejection over Kaler, the US HHS and Tchan was previously described.
As previously discussed, Tchan taught administering a 3 mg subcutaneous injection, and the US HHS taught dosages per mL (e.g., reads on the instant claim 48). Additionally, the US HHS taught reconstitution in 0.9 % NaCl and 500 µg elemental copper per vial, which reads on the instant claims 49-51. The motivation to combine Kaler with Tchan and the US HHS was previously discussed.
Regarding claim 52, Kaler taught from about 50 µg to about 1000 µg, administered as a single dose, multiple doses (e.g., 2, 3, 4, or more doses), or additional doses, as previously discussed.
The instant claim 48 recites about 2900 µg/mL.
Claim 52 recites about 1450 µg once or twice daily, depending on if the subject is greater than or less than 12 months of age.
Tchan taught administering a 3 mg subcutaneous injection, and the US HHS taught dosages per mL. Kaler taught from about 50 µg to about 1000 µg, administered as a single dose, multiple doses (e.g., 2, 3, 4, or more doses), or additional doses. A prima facie case of obviousness exists because of overlap, as discussed above.
Further regarding claim 48, with the combined teachings of Kaler, Tchan and the US HHS, the ordinarily skilled artisan would have had a reasonable expectation of success, in arriving at the claimed amount of copper histidinate, by routine experimentation and without undue experimentation, as previously described (see the Obviousness rejection over Tchan).
Conclusion
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/CELESTE A RONEY/Primary Examiner, Art Unit 1612