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 .
Claim Status
Pending claims 1-3 and 7-23 have been examined on the merits.
Withdrawn Grounds of Rejection
The rejection of claims 1, 3-8, 10, 12-17, 19, and 21- 23 are rejected under 35 U.S.C. 102(a)(l) as being anticipated by Jonas et al. (US20100173994) (“Jonas”) is withdrawn due to the Claim Amendments.
The rejection of claims 2, 9, 11, 18 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Jonas (US 20100173994) as applied to claims 1, 3-8, 10, 12-17, 19, and 21- 23 above, and in view of Gold et al. (Diabetologia) 2007 Apr;50(4):711-9 ("Gold") is withdrawn due to the Claim Amendments.
The rejection of claims 9 is rejected under 35 U.S.C. 103 as being unpatentable over Jonas (US20100173994) as applied to claim 1, 3-8, 10, 12-17, 19, and 21- 23 above, and in further view of Cooper et al. (Drugs) 2011 Jul 9;71(10):1281-320 ("Cooper") is withdrawn due to the Claim Amendments.
Request for Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/25/2025 has been entered.
New Grounds of Rejection due to the Claim Amendments
Claim Rejections - 35 USC § 112
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.
Claims 1-3 and 7-23 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 1 recites a method of treating elevated brain hippocampal copper impaired
cognitive function in a subject with type 2 diabetes mellitus. According to specification (page 53, [0174]):
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Here, the specification defines “elevated” copper mainly based to serum free copper values (e.g., at least about 10 mcg free copper/dL of serum) and urinary copper analysis. However, the specification fails to provide or describe the direct measurement, quantification of copper levels specifically within the hippocampus, and does not establish which exact serum copper levels correspond to elevated hippocampal copper levels. The specification only references to copper levels in the hippocampal tissue mainly derived from post-mortem analysis, rather than living subjects in need of treatment (specification, page 59-62). Thus, post mortem tissue analysis does not establish that Applicant possessed a method for identifying or treating elevated hippocampal copper in a living subject, nor does it clearly disclose that such copper levels can be measured, monitored, or normalized during treatment of a living subject. Therefore, a person of ordinary skill in the art (POSITA) would recognize that the specification does not describe any methodology by which hippocampal copper in a living subject may be assessed or used as guidance in a method of treating elevated brain hippocampal copper.
Furthermore, claim 2 recites “elevated hippocampal copper levels in said subject are normalized.” The specification fails to provide any method capable of normalizing hippocampal copper levels in a living subject. The quantification data supporting such elevation are derived from post-mortem human brain tissue, rather than from living subjects (specification, page 59-62). While the specification (page 16, [0062]) makes reference to systemic copper measurement, such as serum or urinary copper levels, and discusses maintaining copper within about 70 % to about 110 % of normal, however, the specification fails to define what constitutes normal hippocampal copper levels in vivo, or establish correlation between systemic copper measurements and normalization of hippocampal copper. Thus, the specification clearly fails to demonstrate possession of the claimed invention of hippocampal copper normalization. This is because the specification does not describe how hippocampal copper levels are measured, monitored, or determined to be normalized in a subject receiving therapy.
The specification’s failures to disclose a proper methodology by which hippocampal copper in a living subject may be assessed and normalized, supports the conclusion that the specification lacks adequate written description of the claimed subject matter indicating that Applicant was not in possession of a method of treating elevated brain hippocampal copper at the time of filling of the instant application in view of the disclosure of the application as filed.
New Grounds of Rejection due to the Claim Amendments
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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, 3 and 7-23 are rejected under 35 U.S.C. 103 as being unpatentable over Jonas (US 20100173994) in view of Gold et al. (Diabetologia) 2007 Apr;50(4):711-9 and Squitti et. al., J Alzheimers Dis. 2017;56(3):1055-1064.
Regarding claims 1 and 14, Jonas (page 3 and 13-14) teaches a pharmaceutical composition comprising triethylenetetramine compounds, including but not limited triethylenetetramine disuccinate, to treat a human subject with undesired copper levels, including those with type 2 diabetes, as an example. Jonas (page 13, [0181] bridged page 14) teaches that triethylenetetramine compounds, including triethylenetetramine disuccinate, can be administered orally within the range from about 1 mg to about 2400 mg per day (in single or divided doses). Jonas (page 1, [0004]; page 14, [0191]-[0192]) teaches that triethylenetetramine compounds are useful for copper-related neurogenerative disease including Alzheimer’s, Parkinson’s and Wilson’s disease. Given that triethylenetetramine compounds is a selective copper-chelating agent used clinically to remove excess copper from organs including the brain in Wilson’s disease, thus, a person of ordinary skill in the art (POSITA) would infer that triethylenetetramine compounds would chelate excess copper in the brain tissue, leading to the extract of accumulated copper from affected brain regions.
Jonas, however, does not explicitly teach compound is capable of reducing elevated hippocampal copper levels.
Squitti (page 1055-1056 and 1060-1061) teaches that patients with type2 diabetes exhibit elevated of free copper, which drives the disease progression; thus, motivating copper-lowering therapy as discussed by Jonas. In support of that, Gold (page 711-712 and 716-718) teaches the hippocampus is the earliest and primary site of type 2 diabetes associated with brain damage, indicating hippocampal region as a target for therapeutic intervention. Therefore, it would have being obvious to a POSITA to modify Jonas’ teachings in view of Squitti’s and Gold’s disclosure to arrive at the claimed invention, a therapeutic approach of chelating copper in type diabetes. Furthermore, regardless of where copper is accumulated, triethylenetetramine compounds such as triethylenetetramine disuccinate is a well-known selective copper chelator that systemically removes excess copper from diabetic condition (heart, kidney, retina, and etc), Wilson’s, Alzheimer’s, and Parkinson’s disease (the brain). Therefore, a POSITA would recognize that administering triethylenetetramine disuccinate naturally encompassing the brain including hippocampus, as it is the earliest-affected brain region in type 2 diabetes, as disclosed by Gold. For this reason, the instant claims are an obvious routine extension of the combined teachings of Jonas, Gold and Squitti, because the systemic distribution of copper removal inherently encompasses chelating any copper excess in the body, including the brain.
Regarding claim 3, Jonas, as applied to claim 1 above, (page 4, [0046]; page 15, [0195]) teaches a pharmaceutical composition comprising triethylenetetramine compounds and one or more pharmaceutically acceptable excipients or carriers; which can be a delayed release composition.
Regarding claims 7-8, Jonas (page 3) teaches polymorphs of various triethylenetetramine salts, including triethylenetetramine disuccinate, triethylenetetramine tetrahydrochloride, and triethylenetetramine Dihydrochloride, and also discloses the crystalline forms of triethylenetetramine disuccinate anhydrate.
Regarding claim 9, Jonas teaches about Alzheimer’s but does not explicitly use the term subject ‘shows signs of cerebral degeneration.’
However, Cooper at page 1309 discloses that diabetic patients with cerebrovascular disorders might exhibit signs of cerebral degeneration. This is because, Cooper at page 1309 discloses that defective copper regulation and oxidative stress in cerebral vessels in Alzheimer and vascular dementia patients with type 2 diabetes show copper overload, suggesting a shared pathological mechanism involving cerebrovascular damage. Given the association of diabetes with vascular complication, particularly in the brain, it is reasonable for one of ordinary skill in the art to consider diabetic patients with affected cerebral vessels could potentially experience degeneration as a result of these vascular and metabolic disorder. Given this, it would have been obvious to one of ordinary skill in the art to consider combining the teachings of Jonas and Cooper and could expect triethylenetetramine compounds to similarly improve signs of cerebral degeneration by reducing copper levels, as also observed with patients with Wilson’s disease.
Regarding claim 10, Jonas (page 14) teaches that the pharmaceutical composition is applicable for cognitive impairment like Alzheimer’s disease. Therefore, a method of treating Alzheimer’s inherently includes cognitive decline and dementia.
Regarding claim 11, Jonas does not explicitly teach diminished spatial memory or ability to remember directions, locations, and orientation.
However, Gold (page 712) teaches that type 2 diabetes is associated with cognitive impairment, including reduction in cognitive functioning and brain damage or atrophy. Gold (page 712 and 716) teaches type 2 diabetes causes brain damage and lowers memory performance, which may result in a decline of spatial memory and orientation. Given that improvement in diabetes control is linked to better cognitive function, it would be obvious to one of ordinary skill in the art to consider combining the teachings of Jonas and Gold in treating diminished spatial memory in patient with diabetes with triethylenetetramine compounds, and arrive at the claim invention.
Regarding claim 12- 13, Jonas teaches (page 15) teaches the use of triethylenetetramine disuccinate anhydrate with an additional hypoglycemic agent, such as metformin, a biguanide, to treat type 2 diabetes.
Regarding claim 15, Jonas (page 15) teaches pharmaceutical compositions, including tablets, capsules and other oral delivery forms and formulations.
Regarding claims 16-17 and 19, Jonas (page 13-14) teaches that triethylenetetramine compounds, including salts like triethylenetetramine dihydrochloride and triethylenetetramine disuccinate, may be administered within the range of about 1 mg to about 2400 mg per day (in single or divided doses). While Jonas does not explicitly mention BID, TID or QID, however, it is known in the that art that “divided dose prescription” refers to splitting a medication’s total daily amount into multiple, smaller doses to be taken throughout the day, which commonly means BID, TID or QID administration.
Regarding claim 18 and 20, Jonas at page 13- 14 teaches that triethylenetetramine compounds, including salts like triethylenetetramine disuccinate, may be administered within the range of 1 mg to 2400 mg per day (in single or divided doses). Jonas does not teach triethylenetetramine disuccinate in an amount of about 2800 mg daily or divided dose. However, an increase from 2400 to 2800 mg is a routine optimization effort to enhance therapeutic effectiveness. Therefore, such adjustment falls within standard pharmaceutical practice and do not reflect inventive step. In addition, “[W]here 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 2141(11).
Regarding claim 21, The instruction for use of the compound is not considered a limitation as it is not functionally related. Therefore, the subject matter in this claim is treated the same as claim 1 and rejected for the same reason. See MPEP 2112.01
Regarding claim 22, The instruction for use of the compound is not considered a limitation as it is not functionally related. Therefore, the subject matter in this claim is treated the same as claim 5 and rejected for the same reason. See MPEP 2112.01
Regarding claim 23, The instruction for use of the compound is not considered a limitation as it is not functionally related. Therefore, the subject matter in this claim is treated the same as claim 8 and rejected for the same reason. See MPEP 2112.01
However, nonetheless, Jonas (page 32) teaches crystalline form of diethylene tetramine disuccinate.
Subject Matter Free of the Art of Record
The subject matter of claim 2 is free of the art of record. The closest prior art Jonas et al. (US20100173994) teaches a pharmaceutical composition comprising triethylenetetramine compounds, including but not limited triethylenetetramine disuccinate, to treat a human subject with undesired copper levels, including those with type 2 diabetes. However, there is no motivation for a POSITA to modify the teaching of Jonas to arrive at the claimed invention of hippocampal copper normalization. However, the claim is not allowed because of its dependency on a rejected claim. As a result, until this issue is remedied or resolved; the claim cannot be subject of allowance.
Maintained Rejection
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.
Claims 1, 3, 7- 8, 10, 14- 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 26, 29, 40, 44-46 of U.S. Patent No. 7,928,094 in view of Jonas (US 20100173994), Gold et al. (Diabetologia) 2007 Apr;50(4):711-9 and Squitti et. al., J Alzheimers Dis. 2017;56(3):1055-1064.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims pharmaceutical salts of the same compound:
Claims 1-6, 26, 29, 40, 44-46 of the US patent ‘094 are drawn to a method of treating a human for one or more conditions associated with long-term complications of diabetes such as, with a triene or triethylenetetramine that chelates copper, reading on instant claim 1, 3, 7-8, 10, 14- 20. For example, US patent ‘094 discloses methods of treating diabetes and long-term diabetic complications by administering a triene, including triethylenetetramine, that binds copper 9-200 mg/kg per day, in oral dosage to treat various complications of diabetes, including neuropathy and microvasculature which can affect cognitive function, read on the instant claim 1, 3, 7-8, 10, 14- 20. While the instant claims are directed to treating impaired cognitive function in subjects with type 2 diabetes by administering triethylenetetramine disuccinate, lowering copper level systemic would inherently include the brain and hippocampus region. The fact that both the instant claims and US patent ‘094 rely on the same active chelating moiety, the same copper-chelating mechanism, overlapping dosage ranges, and the same therapeutic approach of treating diabetes related pathology; therefore, it is then apparent that additional limitations directed to hippocampal copper sole represent an obvious narrowing and inherent properties of the previous claimed method of US patent ‘094 in view of Jonas, Gold, and Squitti. It is important to note that US patent ‘094 recites “a long-acting release form of a triene salt is administered.” Thus, a POSITA would recognize that triethylenetetramine as the triene which may be administered as triene salts. It would also have been obvious to a POSITA, in view of Jonas, that triethylenetetramine disuccinate is known in the art to treat diabetic complication, which falls within the scope of the disclosed triene salts. Thus, US patent ‘094 does not need to explicitly discloses all triene salts, because a POSITA would readily recognize that triethylenetetramine disuccinate as merely an obvious species within the disclosed genus of triene salts. Therefore, it would have been obvious that a POSITA to modify the disease state and apply the same active compound to treat different diabetes complication, including cognitive function. Therefore, the instant claims are an obvious variation of US patent ‘094 because both teaches a triene compound, a copper chelator, and utility, diabetes.
Claims 1, 3- 8, 10, 14- 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1- 2, 4- 9 of U.S. Patent No. 11,419,831 in view of Jonas (US 20100173994), Gold et al. (Diabetologia) 2007 Apr;50(4):711-9 and Squitti et. al., J Alzheimers Dis. 2017;56(3):1055-1064.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims pharmaceutical salts of the same compound:
Claims 1- 2, 4- 9 of the US patent ‘831 are to a method of treating a subject with but not limited to diabetic heart diseases with a therapeutic effective amount of a succinic acid addition salt of triethylenetetramine, and a daily dose to about 5 mg to about 1,100 mg/day, reading on claims 1, 3, 7- 8, 10, 14- 20. The instant claims similarly also recite methods of treating subjects with type 2 diabetes by administering triethylenetetramine disuccinate, and a daily dose to about 1050 mg to about 5600 mg/day in a subject diabetic patient with an elevated hippocampal copper. Although the instant claims differ in targeted tissue (hippocampus vs heart/vasculature), therapeutic endpoint (reduction of copper level) and dose range are not patentably distinct; because the instant claims are clearly an obvious variation of the US patent ‘831, which is to treat a diabetic patient with a capper chelator, triethylenetetramine disuccinate, which is a is essentially a triethylenetetramine complexed with succinic acid to form a stable salt complex. Therefore, the overlap in therapeutic targets and the utilization of the same compound indicates that the instant claims essentially repeat the teachings of the US patent ‘831 without presenting any distinct inventive concept. Therefore, it is obvious that a POSITA recognize that both patents target the same underlying issue of copper accumulation and employ the same therapeutic compound. Therefore, the instant claims merely represent an attempt to claim an additional use of an already known treatment without presenting any patentably distinguishing or significant differences warranting of an allowance.
Response to Arguments
Applicant argues that Gold studies mainly focus on the association that exists between cognitive changes and type 2 diabetes. It was also disclose that glycemic control (HbA1c) was found to be the main factor and predictor of changes in in hippocampal volume, and there is no mention of association between copper level and hippocampal damage. Applicant’s argument is not persuasive because Gold (page 712) clearly teaches
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This clearly establishes hippocampus as the primary, predictable type 2 diabetes brain target regardless of the mechanism. In fact, Gold does identify the exclusive biochemical mechanism responsible the brain damage in that region. The finding that HbA1c correlates with hippocampal volume loss does not negate the role of other pathogenic contributor, including metal dysregulation. As evidence by Squitti, demonstrating, systemic free copper drives type 2 diabetes progression via insulin resistance, leading to poor glycemic control or elevated HbA1c. Thus, glycemic dysregulation and copper overload are not mutually exclusive explanation; instead, copper dysregulation is a known upstream factor that can contribute to worsened glycemic control, according to Squitti. Therefore, the combined teachings of Gold and Squitti clearly point to copper overload contributes to diabetes progression, thus, hippocampus region would be affected in diabetic patient. This creates a motivation for a POSITA to target hippocampus region to reverse diabetic copper overload in neural tissue and improve insulin sensitivity.
Applicant argues that reliance on the combined teachings of Jonas and Cooper, disclosing the use of triethylenetetramine disuccinate to treat Alzheimer’s disease is inaccurate and inapplicable because Alzheimer’s disease is known to being associated with copper deficiency. Applicant’s argument is not persuasive,because Applicant significantly oversimplifies the prior art regarding copper homeostatic in Alzheimer’s disease and fails to recite the prior art actually teachings. For example, Cooper discloses that triethylenetetramine disuccinate as a useful therapeutic agent for both diabetes and neurodegenerative disorders, including Alzheiemer’s disease, and further characterizes these conditions as involving copper-related tissue damage and dysregulated copper metabolism rather than uniform copper deficiency. In addition, Cooper points to the complexity of Alzheimer’s disease involving redox-active copper level contribute to oxidative stress and amyloids pathology, even where total or tightly bound copper levels may be reduced. Thus, a POSITA would understand that selective chelation of harmful copper species, rather than global copper depletion, is therapeutically desirable. Therefore, contrary to Applicant’s assertion, the explicit inclusion of Alzheimer’s disease among condition treatable with triethylenetetramine disuccinate, according to Cooper’s disclosure, clearly demonstrates that a POSITA would not view copper chelation as undesirable, but rather as a viable strategy for addressing copper-mediated neurogenerative mechanisms.
In response to applicant's arguments against the references individually, 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, it is important to highlight that that the combined teachings of Jonas, Gold and Squitti clearly establish hippocampus as the primary, predictable type 2 diabetes brain target and lack of glycemic control significantly affects this process. Given that copper dysregulation is a hallmark of various conditions such as Alzheimer and diabetes, for example, the therapeutic effect of copper antagonists would logically extend to any disease where copper plays a role, even if the prior art does not disclose each affected tissue.
Double patenting
Applicant argues US patent ‘831 is limited to administration of about 5 mg to about 1100 mg of a succinic acid addition salt of triethylenetetramine but does not explicitly teach triethylenetetramine disuccinate, or elevated hippocampal copper levels. Applicant’s argument is not persuasive because US patent ‘831 discloses succinic acid addition salt of triethylenetetramine, which is recognized in the art as the same type of salt as triethylenetetramine disuccinate. Thus, US patent ‘831 teaches both the salt and diabetic patient, contrary to Applicant’s assertion. Furthermore, US patent ‘831 explicitly discloses copper-associated pathology, including but not limited to cerebrovascular arteries, which a POSITA would recognize to indicate application of the same copper-lowering therapy to central nervous system region affected by copper dysregulation, which inherently includes hippocampus region. Regarding dosage, Applicant fails to note that US patent ‘831 dosage ranges overlap with that of the instant claims; which in itself represent an optimization of the dosing taught by US patent ‘831.
Applicant also argues that US patent ‘094 does not teach triethylenetetramine disuccinate, thus double patenting is not valid. Applicant’s argument is not persuasive, as US patent ‘094 explicitly discloses a method of treating diabetic complications by administering triethylenetetramine, including demonstration “a long-acting release form of a triene salt is administered.” Thus, a POSITA would recognize that triethylenetetramine as the triene which may be administered as triene salts. It would also been obvious to a POSITA, in view of Jonas, that triethylenetetramine disuccinate is known in the art to treat diabetic complication, which falls within the scope of the disclosed triene salts. Thus, US patent ‘094 does not need to explicitly discloses all triene salts, because a POSITA would readily recognize that triethylenetetramine disuccinate as merely an obvious species within the disclosed genus of triene salts.
Conclusion
Therefore, claims 1, 3 and 7-23 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PIERRE PAUL ELENISTE whose telephone number is (571)270-0589. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm (EST).
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/P.P.E./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622