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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/3/2025 has been entered.
Status
Claims 26-27 are pending. Claim 27 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species. Therefore, Claim 26 is under examination.
Election/Restrictions
Applicant elected without traverse Group 1 (compounds) and
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as the elected compound in the reply filed on 10/26/2023.
Therefore, Claim 26 is presented for examination.
Claim Rejections - 35 USC § 103
Rejection Maintained
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 26 is rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (US 2016/0326126 A1) in view of Jornada et al. (Molecules. 2016 Jan; 21(1): 42. Published online 2015 Dec 29. doi: 10.3390/molecules21010042).
Claimed Invention
The claims are drawn to a pharmaceutical composition suitable for intravenous injection, the pharmaceutical composition comprising a liquid carrier and an effective amount of a compounds of formula I
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such as
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Prior art
Yang teaches compounds of formula (I)
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, wherein EDG is an electron donor group, EWG is electron withdrawing group; and WSG is a water-soluble group. See 0004-0005. An example taught by Yang is Compound 1 identified in Figure 1.
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See Fig. 1B; see also 0939. The water-soluble group (WSG) of the compound is represented by the tail containing the polyethylene glycol group:
“In some compounds of Formula I, WSG is polyethylene glycol, polypropylene glycol, co-polymer of polyethylene glycol and polypropylene glycol, or alkoxy derivatives thereof.
In some compounds of Formula I, WSG is
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”
See 0020.
The disclosure provides novel compounds that are employed in the detection, diagnosis, treatment, and monitoring of diseases or conditions associated with protein aggregation or protein misfolding. See 0228. The compositions may be employed via intravenous administration using pharmaceutically acceptable liquid carriers See 0539, 0566, and 0588.
While Yang teaches compounds including Compound 1 can be used in pharmaceutical compositions that may further comprising a liquid carrier and may be suitable for intravenous administration, Compound 1 differs from the claimed compound because reference Compound 1 has a methoxy (-OCH3) group within the water-soluble group at the right end of the reference structure instead of
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such as
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at the right end of the claimed structure:
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However, it was already known that phosphate groups are added to pharmaceutical compounds to increase the water solubility of same. For example, Jornada teaches phosphate ester compounds are relatively stable when free in metabolic surroundings and that combining a phosphate with a drug (phosphate-prodrug approach) has been successfully used to enhance the solubility and availability of the drug. See p. 17, section ‘8. Phosphate Prodrugs’, first par. Several examples are provided by Jornada demonstrating increased solubility of pharmaceutical compounds using the addition of a phosphate group to the pharmaceutical compounds. See section ‘8. Phosphate Prodrugs’ at pp. 17-20. One example, in Figure 25 shows that the addition of a phosphate to a pharmaceutical agent increased the solubility of the agent by >700-fold and another at >1600-fold. See Figure 25. Another example shows that the addition of phosphate to a pharmaceutical agent increased the solubility by >50,000 fold. See Figure 26. Increasing solubility enables formulation of injectable solutions. See p. 25, 1st full para.
One of ordinary skill in the art would have found it obvious to incorporate a phosphate group in the water-soluble group of a compound of formula (I) such as Compound 1 because Yang exemplifies
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as a compound of Formula 1 wherein the water-soluble group includes polyethylene glycol or alkoxy derivatives thereof such as including the structure
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while Jornada teaches that phosphate can be added to pharmaceutical compounds in order to enhance water solubility. The artisan would have added the phosphate group to Compound 1 to arrive at the instant compound in order to enhance the water solubility of the compound. The artisan would have had a reasonable expectation of success that the addition of a phosphate group at the end of the water-soluble group would impart its water solubility enhancing effects given that the prior art recognized that phosphate ester added to the pharmaceutical compounds increases their water solubility.
The suggested compound
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meets the limitations of Claims 26.
Response to arguments
Applicant argues that the phosphate group is not cleaved in the body which is unexpected. This is not persuasive because there is no evidence that it is unexpected.
Applicant states that the present invention is directed to a pharmaceutical composition suitable for intravenous injection comprising a liquid carrier and an effective amount of a compound represented by the instant formula
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. Applicant further states that although Jornada discloses phosphate-containing compounds, Jornada concerns forming phosphate prodrugs for the oral delivery of poorly soluble drugs. Thus, Applicant argues that a POSA would recognize the significance of intestinal alkaline phosphatases in the context of phosphate prodrugs and would consider this approach suitable for orally administered drugs. Applicant's arguments have been fully considered but have not been found persuasive because the Jornada reference is not as limiting as suggested by Applicant’s argument. For instance, Jornada teaches increasing solubility enables formulation of injectable solutions. See p. 25, 1st full para. Jornada further teaches to “overcome the poor solubility in water of SNS-314 (78), an aurora kinase inhibitor, a prodrug was designed with several moieties attached to the parent drug, such as acyl-oxymethylene, amine-containing acyl-oxymethylene and phosphate group. Prodrug 79, a phosphate-ester derivative, was 335-fold more water soluble than the parent drug (Figure 30). Moreover, although the acyl-oxymethylene derivatives showed increased solubility (8–20-fold), they were much less effective than the phosphate-ester prodrug [108].” In support of this, Jornada references Oslob et al. (“Water-soluble prodrugs of an Aurora kinase inhibitor.” Bioorg. Med. Chem. Lett. 2009;19:1409–1412. doi: 10.1016/j.bmcl.2009.01.043 - attached) which teaches the phosphate ester prodrug was more effective than the drug in intravenous administration. Oslob studied the effectiveness of Compound 1,
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, as compared to prodrugs thereof:
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Oslob described the prodrugs having improved aqueous solubility profiles. In particular, phosphonooxymethyl-derived prodrug 2g has significantly enhanced solubility and is converted to the biologically active parent (1) following iv, i.e., intravenous, as well as po, i.e., oral, administration to rodents. See Oslob at abstract; see also Figure 1 at p. 1409 and Figure 2 at p. 1410. Thus, Jornada is not limited to the use of phosphate esters for oral administration only. As such, the POSA would have understood that phosphate ester prodrug can be used to increase solubility of the drug as disclosed by Jornada including for intravenous use. Given that Yang and Jornada teach intravenous administration, there is no need for the references to explain how the technologies described can be modified to avoid oral administration as argued by Applicant in the paragraph bridging pages 5 and 6 of the remarks.
Applicant further makes unsubstantiated conclusory statements about calcium in the body binding to phosphate leading to reduced amounts of free calcium. This is not persuasive because the record does not support the position that the occurrence of this alleged phenomenon would dissuade one from making an intravenous formulation of the phosphate ester prodrug instantly claimed.
Double Patenting
Rejection maintained
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.
Response to arguments against ODP rejections
Applicant relies on the above arguments to assert that the double patenting rejections should be removed. However, for the reasons set forth above, the rejections are maintained.
A. Claim 26 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 10,005,745 (“reference” or “Yang”– specification published in 2016 and is available as prior art) in view of Jornada et al (cited above).
Claimed Invention
The claims are drawn to a pharmaceutical composition suitable for intravenous injection, the pharmaceutical composition comprising a liquid carrier and an effective amount of a compounds of formula I
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Reference art
The reference claims are drawn to compounds of formula (Ic)
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(see reference Claim 1) and pharmaceutical compositions containing them and liquid carriers such as DMSO, ethanol, aqueous phosphate buffer, and others (see Claim 19). EDG is defined as an electron donor group (see reference col. 1), EWG as an electron withdrawing group (see reference col. 3), and WSG as a water-soluble group (see reference col. 3). An example taught by the reference is Compound 1 identified in Figure 1.
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See Fig. 1B; see also col. 299. The water-soluble group (WSG) of the compound is represented by the tail containing the polyethylene glycol group:
“In some compounds of Formula I, WSG is polyethylene glycol, polypropylene glycol, co-polymer of polyethylene glycol and polypropylene glycol, or alkoxy derivatives thereof.
In some compounds of Formula I, WSG is
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”
See col. 4.
The disclosure provides novel compounds that are employed in the detection, diagnosis, treatment, and monitoring of diseases or conditions associated with protein aggregation or protein misfolding. See col. 43. The compositions may be employed via intravenous administration using pharmaceutically acceptable liquid carriers. See col. 43, particularly the paragraph starting at line 23; see also col. 203, line 39, 43; see also col. 213, line 40.
While the Yang reference claims compounds including Compound 1 can be used in pharmaceutical compositions that may further comprising a liquid carrier and may be suitable for intravenous administration, the Yang reference Compound 1 differs from the claimed compound because Compound 1 has a methoxy group instead of Formula I wherein R1 is
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, wherein X = O and R11 = H, in the claimed compound within the water-soluble group:
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vs
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However, it was already known that phosphate groups are added to pharmaceutical compounds to increase the water solubility of same. For example, Jornada teaches phosphate ester compounds are relatively stable when free in metabolic surroundings and that combining a phosphate with a drug (phosphate-prodrug approach) has been successfully used to enhance the solubility and availability of the drug. See p. 17, section ‘8. Phosphate Prodrugs’, first par. Several examples are provided by Jornada demonstrating increased solubility of pharmaceutical compounds using the addition of a phosphate group to the pharmaceutical compounds. See section ‘8. Phosphate Prodrugs’ at pp. 17-20. One example, in Figure 25 shows that the addition of a phosphate to a pharmaceutical agent increased the solubility of the agent by >700-fold and another at >1600-fold. See Figure 25. Another example shows that the addition of phosphate to a pharmaceutical agent increased the solubility by >50,000 fold. See Figure 26. Increasing solubility enables formulation of injectable solutions. See p. 25, 1st full para.
One of ordinary skill in the art would have found it obvious to incorporate a phosphate group in the water-soluble group of a compound of formula (I) such as Compound 1 to form the compound
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because the reference exemplifies
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as a compound of Formula 1 wherein the water-soluble group includes polyethylene glycol or alkoxy derivatives thereof such as including the structure
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while Jornada teaches that phosphate can be added to pharmaceutical compounds in order to enhance water solubility. The artisan would have added the phosphate group to Compound 1 to arrive at the instant compound in order to enhance the water solubility of the compound. The artisan would have had a reasonable expectation of success that the addition of a phosphate group at the end of the water-soluble group would impart its water solubility enhancing effects given that the reference art recognized that phosphate ester added to the pharmaceutical compounds increases their water solubility.
The Compound
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meets the limitations of Claims 26.
B. Claim 26 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,370,345 in view of Yang et al. (US 2016/0326126 A1) and Jornada et al (cited above).
Claimed Invention
The claims are drawn to a pharmaceutical composition suitable for intravenous injection, the pharmaceutical composition comprising a liquid carrier and an effective amount of a compounds of formula I
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such as
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Reference art
The reference claims are drawn to methods of using compounds of formula (Ic)
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to monitor response to a treatment of a patient having a disease or condition characterized by amyloid deposit in a body part or a body area of the patient, comprising: (i) forming a detectable complex in the body part or the body area following the treatment by contacting an effective amount of a compound of Formula Ic with the amyloid deposit; and (ii) detecting the detectable complex, wherein a decrease of detectable complex as compared to before the treatment indicates that the patient is responsive to the treatment. See reference Claim 1. An example of the compound is
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wherein n is an integer from 2 to 10. See Claim 12. Claim 18 specifically identifies
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. See Claim 18.
The reference compound differs from the claimed compound because the reference claims do not teach a liquid carrier in the pharmaceutical suitable for intravenous use and the reference compound has a methoxy group instead of Formula I wherein R1 is
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, wherein X = O and R11 = H, in the claimed compound within the water-soluble group:
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The compound is similar to the compounds disclosed by Yang and have similar utility. Yang teaches compounds of formula (I)
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, wherein EDG is an electron donor group, EWG is electron withdrawing group; and WSG is a water-soluble group. See 0004-0005. An example taught by Yang is Compound 1 identified in Figure 1.
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See Fig. 1B; see also 0939.
The water-soluble group (WSG) of the compound is represented by the tail containing the polyethylene glycol group:
“In some compounds of Formula I, WSG is polyethylene glycol, polypropylene glycol, co-polymer of polyethylene glycol and polypropylene glycol, or alkoxy derivatives thereof.
In some compounds of Formula I, WSG is
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”
See 0020.
The disclosure provides novel compounds that are employed in the detection, diagnosis, treatment, and monitoring of diseases or conditions associated with protein aggregation or protein misfolding. See 0228. The compositions may be employed via intravenous administration using pharmaceutically acceptable liquid carriers See 0539, 0566, and 0588.
It was already known that phosphate groups are added to pharmaceutical compounds to increase the water solubility of same. For example, Jornada teaches phosphate ester compounds are relatively stable when free in metabolic surroundings and that combining a phosphate with a drug (phosphate-prodrug approach) has been successfully used to enhance the solubility and availability of the drug. See p. 17, section ‘8. Phosphate Prodrugs’, first par. Several examples are provided by Jornada demonstrating increased solubility of pharmaceutical compounds using the addition of a phosphate group to the pharmaceutical compounds. See section ‘8. Phosphate Prodrugs’ at pp. 17-20. One example, in Figure 25 shows that the addition of a phosphate to a pharmaceutical agent increased the solubility of the agent by >700-fold and another at >1600-fold. See Figure 25. Another example shows that the addition of phosphate to a pharmaceutical agent increased the solubility by >50,000 fold. See Figure 26. Increasing solubility enables formulation of injectable solutions. See p. 25, 1st full para.
One of ordinary skill in the art would have found it obvious to incorporate a phosphate group in the water-soluble group of a reference compound such as
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to form the instant compound
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because the reference discloses
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which is similar to the compounds of Yang having similar utility and wherein Yang teaches the water-soluble group includes polyethylene glycol or alkoxy derivatives thereof such as including the structure
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while Jornada teaches that phosphate can be added to pharmaceutical compounds in order to enhance water solubility. The artisan would have added the phosphate group to reference compound to arrive at the instant compound in order to enhance the water solubility of the reference compound. The artisan would have had a reasonable expectation of success that the addition of a phosphate group at the end of the water-soluble group would impart its water solubility enhancing effects given that the reference art recognized that phosphate ester added to the pharmaceutical compounds increases their water solubility.
One of ordinary skill in the art would have found it obvious to incorporate the suggested compound in an formulation with a liquid carrier for intravenous employment because Yang teaches that the reference compound is one of several structurally similar compound that can be combined with a liquid carrier and employed intravenously. The artisan would have had a reasonable expectation of success that the suggested compound can be combined with a liquid to provide an intravenous formulation.
The Compound
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meets the limitations of Claims 26.
C. Claim 26 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,934,264 (“reference”) in view of Yang et al. (US 2016/0326126 A1) and Jornada et al (cited above).
Claimed Invention
The claims are drawn to a pharmaceutical composition suitable for intravenous injection, the pharmaceutical composition comprising a liquid carrier and an effective amount of a compounds of formula I
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such as
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Reference art
The reference claims are drawn to compounds of formula Ic and the methods of using compounds of formula (Ic)
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to detect amyloid or amyloid like protein and monitor response to a treatment of a patient having a disease or condition characterized by amyloid deposit in a body part or a body area of the patient. The reference claims teach pharmaceutical compositions containing the compounds and liquid carriers such as DMSO, ethanol, aqueous phosphate buffer, and others (see Claim 11). The methods comprising contacting an effective amount of a compound of Formula Ic with the amyloid deposit and detecting the detectable complex. See reference Claims 1, 18 and 19. Claim 18 specifically identifies
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. See Claim 18.
The reference compound differs from the claimed compound because the reference claims do not teach a liquid carrier in the pharmaceutical suitable for intravenous use and the reference compound has a methoxy group instead of Formula I wherein R1 is
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, wherein X = O and R11 = H, in the claimed compound within the water-soluble group:
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The compound is similar to the compounds disclosed by Yang and have similar utility. Yang teaches compounds of formula (I)
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, wherein EDG is an electron donor group, EWG is electron withdrawing group; and WSG is a water-soluble group. See 0004-0005. An example taught by Yang is Compound 1 identified in Figure 1.
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See Fig. 1B; see also 0939.
The water-soluble group (WSG) of the compound is represented by the tail containing the polyethylene glycol group:
“In some compounds of Formula I, WSG is polyethylene glycol, polypropylene glycol, co-polymer of polyethylene glycol and polypropylene glycol, or alkoxy derivatives thereof.
In some compounds of Formula I, WSG is
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”
See 0020.
The disclosure provides novel compounds that are employed in the detection, diagnosis, treatment, and monitoring of diseases or conditions associated with protein aggregation or protein misfolding. See 0228. The compositions may be employed via intravenous administration using pharmaceutically acceptable liquid carriers See 0539, 0566, and 0588.
It was already known that phosphate groups are added to pharmaceutical compounds to increase the water solubility of same. For example, Jornada teaches phosphate ester compounds are relatively stable when free in metabolic surroundings and that combining a phosphate with a drug (phosphate-prodrug approach) has been successfully used to enhance the solubility and availability of the drug. See p. 17, section ‘8. Phosphate Prodrugs’, first par. Several examples are provided by Jornada demonstrating increased solubility of pharmaceutical compounds using the addition of a phosphate group to the pharmaceutical compounds. See section ‘8. Phosphate Prodrugs’ at pp. 17-20. One example, in Figure 25 shows that the addition of a phosphate to a pharmaceutical agent increased the solubility of the agent by >700-fold and another at >1600-fold. See Figure 25. Another example shows that the addition of phosphate to a pharmaceutical agent increased the solubility by >50,000 fold. See Figure 26. Increasing solubility enables formulation of injectable solutions. See p. 25, 1st full para.
One of ordinary skill in the art would have found it obvious to incorporate a phosphate group in the water-soluble group of a reference compound such as
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to form the instant compound
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because the reference discloses
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which is similar to the compounds of Yang having similar utility and wherein Yang teaches the water-soluble group includes polyethylene glycol or alkoxy derivatives thereof such as including the structure
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while Jornada teaches that phosphate can be added to pharmaceutical compounds in order to enhance water solubility. The artisan would have added the phosphate group to reference compound to arrive at the instant compound in order to enhance the water solubility of the reference compound. The artisan would have had a reasonable expectation of success that the addition of a phosphate group at the end of the water-soluble group would impart its water solubility enhancing effects given that the reference art recognized that phosphate ester added to the pharmaceutical compounds increases their water solubility.
One of ordinary skill in the art would have found it obvious to incorporate the suggested compound in an formulation with a liquid carrier for intravenous employment because Yang teaches that the reference compound is one of several structurally similar compound that can be combined with a liquid carrier and employed intravenously. The artisan would have had a reasonable expectation of success that the suggested compound can be combined with a liquid to provide an intravenous formulation.
The Compound
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meets the limitations of Claims 26.
D. Claim 26 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,718,596 (“reference”) in view of Yang et al. (US 2016/0326126 A1) and Jornada et al (cited above).
Claimed Invention
The claims are drawn to a pharmaceutical composition suitable for intravenous injection, the pharmaceutical composition comprising a liquid carrier and an effective amount of a compounds of formula I
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such as
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Reference art
The reference claims are drawn to compounds of formula Ie
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. See Claim 1. The utility of the compounds include detection of amyloid or amyloid like proteins. They are designed to exhibit enhanced fluorescence emission upon associating with amyloid or amyloid like proteins as compared to unbound compound. The compounds are included in pharmaceutical compositions containing a pharmaceutically acceptable carrier (see Claim 20) and are useful in methods for treating diseases associated with amyloid or amyloid like proteins. See abstract.
Claim 1 defines the R84 as H and EWG as -CN. Claim 2 defines Ar as
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. Claim 3 defines EDG as
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. Claim 8 specifically identifies the WSG portion as
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. See Claim 8. This reads on the compound
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.
The reference compound differs from the claimed compound because the reference claims do not teach a liquid carrier in the pharmaceutical suitable for intravenous use and the reference compound has a methoxy group instead of Formula I wherein R1 is
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, wherein X = O and R11 = H, in the claimed compound within the water-soluble group:
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vs
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.
The compound is similar to the compounds disclosed by Yang and have similar utility. Yang teaches compounds of formula (I)
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, wherein EDG is an electron donor group, EWG is electron withdrawing group; and WSG is a water-soluble group. See 0004-0005. An example taught by Yang is Compound 1 identified in Figure 1.
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See Fig. 1B; see also 0939.
The water-soluble group (WSG) of the compound is represented by the tail containing the polyethylene glycol group:
“In some compounds of Formula I, WSG is polyethylene glycol, polypropylene glycol, co-polymer of polyethylene glycol and polypropylene glycol, or alkoxy derivatives thereof.
In some compounds of Formula I, WSG is
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”
See 0020.
The disclosure provides novel compounds that are employed in the detection, diagnosis, treatment, and monitoring of diseases or conditions associated with protein aggregation or protein misfolding. See 0228. The compositions may be employed via intravenous administration using pharmaceutically acceptable liquid carriers See 0539, 0566, and 0588.
It was already known that phosphate groups are added to pharmaceutical compounds to increase the water solubility of same. For example, Jornada teaches phosphate ester compounds are relatively stable when free in metabolic surroundings and that combining a phosphate with a drug (phosphate-prodrug approach) has been successfully used to enhance the solubility and availability of the drug. See p. 17, section ‘8. Phosphate Prodrugs’, first par. Several examples are provided by Jornada demonstrating increased solubility of pharmaceutical compounds using the addition of a phosphate group to the pharmaceutical compounds. See section ‘8. Phosphate Prodrugs’ at pp. 17-20. One example, in Figure 25 shows that the addition of a phosphate to a pharmaceutical agent increased the solubility of the agent by >700-fold and another at >1600-fold. See Figure 25. Another example shows that the addition of phosphate to a pharmaceutical agent increased the solubility by >50,000 fold. See Figure 26. Increasing solubility enables formulation of injectable solutions. See p. 25, 1st full para.
One of ordinary skill in the art would have found it obvious to incorporate a phosphate group in the water-soluble group of a reference compound such as
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to form the instant compound
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because the reference discloses
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which is similar to the compounds of Yang having similar utility and wherein Yang teaches the water-soluble group includes polyethylene glycol or alkoxy derivatives thereof such as including the structure
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while Jornada teaches that phosphate can be added to pharmaceutical compounds in order to enhance water solubility. The artisan would have added the phosphate group to reference compound to arrive at the instant compound in order to enhance the water solubility of the reference compound. The artisan would have had a reasonable expectation of success that the addition of a phosphate group at the end of the water-soluble group would impart its water solubility enhancing effects given that the reference art recognized that phosphate ester added to the pharmaceutical compounds increases their water solubility.
One of ordinary skill in the art would have found it obvious to incorporate the suggested compound in an formulation with a liquid carrier for intravenous employment because Yang teaches that the reference compound is one of several structurally similar compound that can be combined with a liquid carrier and employed intravenously. The artisan would have had a reasonable expectation of success that the suggested compound can be combined with a liquid to provide an intravenous formulation.
The Compound
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meets the limitations of Claims 26.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H. Alstrum-Acevedo can be reached on (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRIS E SIMMONS/ Examiner, Art Unit 1629
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622