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 .
DETAILED ACTION
RCE Final Rejection
Review of Claim Status
Claims 1, 3-5 and 12 were pending as of the prior Office Action.
Upon amendment entrance, Claims 2 and 11 remain cancelled.
Upon amendment entrance, Claims 6-10 remain withdrawn.
Claims 1, 3-5 and 12 are currently under examination.
Priority Status
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Receipt is acknowledged of certified foreign copies of papers required by 37 CFR 1.55.
Examiner Responses to Arguments/Amendments
The issues raised in the prior Office Action, are addressed below:
I. Review Response to Declaration Under 37 §1.132 of Joong Myung Cho– Rejection Stands
The declaration under 37 CFR 1.132 filed 06/26/2024 is insufficient to overcome the
rejection of the 103 rejections as set forth in the Office action mailed 02/06/2025 because:
according to MPEP 2143.I.E.
The claimed invention in Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 82 USPQ2d 1321 (Fed. Cir. 2007), was directed to the amlodipine besylate drug product, which was sold in tablet form in the United States under the trademark Norvasc®. Amlodipine and the use of besylate anions were both known at the time of the invention. Amlodipine was known to have the same therapeutic properties as were being claimed for the amlodipine besylate, but Pfizer discovered that the besylate form had better manufacturing properties (e.g., reduced "stickiness").
Pfizer argued that the results of forming amlodipine besylate would have been unpredictable and therefore nonobvious. The court rejected the notion that unpredictability could be equated with nonobviousness here, because there were only a finite number (53) of pharmaceutically acceptable salts to be tested for improved properties.
The court found that one of ordinary skill in the art having problems with the machinability of amlodipine would have looked to forming a salt of the compound and would have been able to narrow the group of potential salt-formers to a group of 53 anions known to form pharmaceutically acceptable salts, which would be an acceptable number to form "a reasonable expectation of success."
The Declaration insufficiency stands.
On its face, pharmaceutically acceptable salts of known active agents are generally obvious in the absence of unexpected results. In this case, the US 8,053,435 B2 (hereinafter “Patent’435”) teaches the base drug and suggests salt forms. While the act of creating a salt is routine, the specific physicochemical properties (solubility, stability, non-hygroscopicity) of a particular salt involves experimental screening, it is not deemed patentable because it requires effort. Identifying a specific salt form from a finite, known list of counterions (e.g., HCI, besylate, phosphate, tartrate) is routine optimization, especially when the resulting properties are predictable based on common pharmaceutical knowledge. Berge, a known prior art, teaches alternative salt forms including the salt of Instant Claim 1.
Also, as seen in the 103 rejections below, this is indicative of KSR Prong B – substitution of one salt form for another salt form. Given the presentation of the data, the combination of Patent’435 & Berge focused on the reasonable expectation of success and the predictability of the results, rather than the effort required.
While the process might involve some routine experimentation, the outcome was not unpredictably superior. In that, the prior art suggests salt formation for improving solubility or stability. The fact that experimentation is required does not make the result non-obvious if the prior art provided a reasonable expectation of success and suggested the pathway taken.
Though the Applicant claims superior stability, solubility, or bioavailability, these are the expected reasons for preparing a salt in the first place. The claimed properties (e.g., increased dissolution, reduced hygroscopicity) are the standard, predictable goals of salt screening. The results are not 'unexpected'—they are the desired and intended outcome of following established pharmaceutical practices.
In this, according to Pfizer Inc. v. Apotex Inc., 480 F.3d 1348 (Fed. Cir. 2007)) when the prior art teaches a method of creating salts and the resulting salt has characteristics expected from that salt type, the salt is obvious. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein).
In this, Examiner does have questions for the Applicant over this specific API with the listed salts.
Is the evidence, in the context of this specific API, less optimal? Depending on the salt, how is Applicants compound salt superior compared to other salts of this API? Applicant has failed to provide comparative evidence showing the claimed salt has unexpectedly superior properties relative to other closely related salt forms of the same drug API.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
II. Response to Non-Statutory Double Patenting Rejections (NSDP)–
Claims 1, 3-5 and 12 are rejected on the ground of NSDP for being unpatentable over Claims 1, 3, 5-6, and 10-13 of (U.S. 8,053,435 B2) in view of Berge.
Applicant argues “The Office has not carried the required obviousness-type showing that the pending claims are not patentably distinct from the claims of Lee I, even considering Berge…. Lee I expressly teaches that its compounds "may be used in the form of pharmaceutically acceptable addition salts formed with an acid or base," and then proceeds to list a broad spectrum of potential acids, including inorganic acids such as hydrochloric, hydrobromic, phosphoric, and sulfuric, as well as organic acids such as acetic, trifluoroacetic, citric, formic, maleic, oxalic, succinic, benzoic, tartaric, fumaric, mandelic, ascorbic, malic, methanesulfonic, and p-toluenesulfonic acids. Lee I, col. 4, lines 1-13.”
The Double Patent Rejection Applicant's arguments filed 02/06/2025 and 01/09/2026 have been fully considered but they are not persuasive for the following reasons stated above as well as the maintained rejections below.
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). As stated in Section I, the Applicant has not provided data that would exemplify a condition of unexpected results as seen by the prior arts disclosed in this Office Action as it being obvious to one in the art.
In view of Applicant’s amendment, the Double Patent Rejection Applicant's arguments filed 02/06/2025 have been fully considered but they are not persuasive; the rejection stands.
III. RCE Maintained Rejections –
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.
Claim 1-5 and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 1, 3, 5-6, and 10-13 of U.S. Patent No. US 8,053,435 B2 in view of Berge et al (for Claim 1: J. Pharmaceutical Sciences Vol. 66, pgs. 1-19; published 1977)(hereinafter “Berge”).
Although the claims at issue are not identical, they are not patentably distinct from each other because the methods and compounds used in the instant claims of [(E)-N1-(3-(dimethylamino)propyl)-N8-hydroxy-2-((naphthalen-1-yloxy)methyl)-2-octenediamide], are similar to the naphthalenyloxypropenyl derivative and contains comparable methods of use in US 8,053,435 B2.
Lee I expressly teaches that its compounds "may be used in the form of pharmaceutically acceptable addition salts formed with an acid or base," and then proceeds to list a broad spectrum of potential acids, including inorganic acids such as hydrochloric, hydrobromic, phosphoric, and sulfuric, as well as organic acids such as acetic, trifluoroacetic, citric, formic, maleic, oxalic, succinic, benzoic, tartaric, fumaric, mandelic, ascorbic, malic, methanesulfonic, and p-toluenesulfonic acids. Lee I, col. 4, lines 1-13.
The claims of the Patent’435 fails to disclose the phosphate salt as the pharmaceutically acceptable salt; though it is mentioned in the specification “the compounds of Formulae 1-4 may be used in the form of pharmaceutically acceptable addition salts formed with an acid or base”(col. 3, lns. 65-67 to col. 4, lns. 1-6); indicating motivation and suggestion for the salt.
However, Berg teaches there are a finite number common pharmaceutically acceptable salts to choose from. Berge teaches the list of FDA approved commercially marketed salts in Table 1 and that phosphoric acid salt forms is one of the FDA approved commercially marketed salt forms to formulate an active pharmaceutical ingredient. Berge additionally states several benefits are gained by formulating different active pharmaceutical ingredients into salt form, including chemical, biological, physical and economical properties of the active pharmaceutical agent (pg. 1, col. 1, para. 1; pg. 2, able 1).
Instant Case Claims
US 8,053,435 B2 Patent Claims
1 and 2– claims the pharmaceutical composition of a compound
[(E)-N1-(3-(dimethylamino)propyl)-N8-hydroxy-2-((naphthalen-1-yloxy)methyl)-2-octenediamide]
Claim 5: A pharmaceutical composition for an anticancer agent comprising the compound of Formula 1, the compound of Formula 2, or a combination thereof according to claim 1
Claim 11: The pharmaceutical composition according to claim 1, wherein Ri is CH2CH2CH2N(CH3)2
[AltContent: textbox (Formula 2)]
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Claim 1 - A naphthalenyloxypropenyl derivative of formula (2) or its pharmaceutically acceptable salt
Claim 3 - A naphthalenyloxypropenyl derivative of formula (2) or its pharmaceutically acceptable salt
Claim 5 - A naphthalenyloxypropenyl derivative of formula (2) or its pharmaceutically acceptable salt..
Claim 6 - The compound of claim 5, which is selected from the group consisting of (Z)-8-(3-(dimethylamino)propylamino)-N-hydroxy-7-((naphthalen-1-yloxy)methyl)oct-6-enamide
Claim 10. An anti-cancer composition comprising a naphthalenyloxypropenyl derivative of claim 3.
Claim 11. An anti-cancer composition comprising a naphthalenyloxypropenyl derivative of claim 5.
Claim 12. An anti-cancer composition comprising a naphthalenyloxypropenyl derivative of claim 7.
Claim 13. The compound of claim 3, wherein R is a C1-3 alkyl substituted with diC1-3 alkylamino group.
C1 - R1 is diC1-3alkylamino
C3 - R1 is diC1-3alkylamino
C5 – R1 is diC1-3alkylamino
C6 - (Z)-8-(3-(dimethylamino)propylamino)-N-hydroxy-7-((naphthalen-1-yloxy)methyl)oct-6-enamide
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It would have been prima facie obvious at the time of the invention to formulate the compound, a naphthalenyloxypropenyl derivative of Formula 1-4, in a phosphoric salt form (in view of the teachings of Lee and Berg) in order to arrive at the instantly claimed species. One of ordinary skill in the art would have utilized the pharmaceutically acceptable phosphoric salt to elicit the advantages disclosed by Lee and Berg.
In doing so, a reasonable expectation of success is likely because (1) Lee teaches that the claimed compound can be formulated as a pharmaceutically acceptable salt coupled with the knowledge that (2) the phosphoric acid salt form is one of the most preferred salt species for formulating medicinal compounds due to the corresponding physiological benefits and ease of synthesis as taught by Lee and Berg.
Claim Rejections - 35 USC § 103
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 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.
Joint Inventors
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, 3-5 and 12 are rejected under 35 U.S.C. 103 as being obvious by US 8,053,435 B2 (Made of Record; hereinafter “Lee”) in view of Berge et al (for Claim 1: hereinafter “Berge”).
a. First Rejection
With respect to Claims, Lee teaches the stereoisomer compound “(Z)-N1-(3-(dimethylamino)propyl)-N8-hydroxy-2-((naphthalen-1-yloxy)methyl)-2-octenediamide” (diC1-3alkylamino -CH2CH2CH2N(CH3)2: col. 2, lns. 52-67 to col. 3, lns. 1-35; Formula 2; claim 13); Lee discloses a diC1-3alkylamino -CH2CH2CH2N(CH3)2: and a general method to make the instant claimed salt species (col. 10, lns. 17-47; col. 28, lns. 20-31).
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With respect to Claims 3-5 and 12, Lee continues to teach “there is provided an anti-cancer composition comprising at least one of the compounds of formulae (1) to (4) or pharmaceutically acceptable salts thereof as an active ingredient” (col. 3, lns. 13-35) and the method of making the alkyl-carbamoyl-naphthalenyl oxyoctenoyl hydroxyamide (col. 3, lns. 65-67) derivatives.
This also includes a pharmaceutical salt step (Formula 2 & Formula 3; col. 4, lns. 1-13; col. 8, lns. 29-67 to col. 9, lns. 1-19; Step 2-5 and 2-7, col. 10, lns. 32-34 & 38-40), indicating the salt product (col. 28, lns. 20-24).
Lee continues to disclose (Claim 3) the composition is a tablet or capsule (col. 28, lns. 38-41) further comprising a coating layer (col. 28, lns. 58-59), and the coating layer coating layer is present in an amount of 1 to 10%, “at least one of the compounds of formulae 1 to 4 (Instant Case Claims Formula) as an active ingredient in an amount ranging from 0.1 to 75 wt%, preferably 1 to 50 wt% (col. 28, lns. 34-36), based on the total weight of the composition by weight based on weight of the tablet or capsule (col. 28, lns. 34-36).
With respect to the dose ranges of claim 3, Lee teaches overlapping ranges at 1 to 10%, (col. 28, lns. 32-36) in an amount ranging from “0.1 to 75 wt%, preferably 1 to 50 wt%, based on the total weight of the composition”, indicating the remaining percent left in the composition is 25-50% constitute “preservatives, stabilizers, wetting agents, emulsifying agents, osmotic pressure-adjusting agents, buffering agents and the like, and may be formulated through a conventional mixing, granulating or coating procedures” (col. 28, lns. 54-58).With Lee using the claimed species, the patent also teaches the free bases of compounds of instant claim 1 as well as compositions and tablet formulations.
Additionally, Lee discloses (Claims 4, 5 and 12) a pharmaceutical composition (col. 28, lns. 24-31) formulated for injection (sterile injectable formulations; col. 28, lns. 51-53) is in a liquid (isotonic solution and suspension; col. 28, lns. 51-53) and a pharmaceutical composition (col. 28, lns. 24-31; col. 28, lns. 51-53) and its use with histone deacetylases (HDACs) teaching “HDAC has been one of targets for the study of anticancer drugs as well as gene expression inhibitors and there have been attempts to develop HDAC inhibitors as anticancer drugs” (col. 10, lns. 17-47; col. 28, lns. 20-23; claims 10-12).
Lee fails to teach the explicit teaching of phosphate salt with the amine of R1; specifically the claimed species (E)-N1-(3-(dimethylamino)propyl)-N8-hydroxy-2-((naphthalen-1-yloxy)methyl)-2-octenediamide’s phosphoric salt form though Lee does teach the Z stereoisomer, (Z)-N1-(3-(dimethylamino)propyl)-N8-hydroxy-2-((naphthalen-1-yloxy)methyl)-2-octenediamide” (diC1-3alkylamino -CH2CH2CH2N(CH3)2: col. 2, lns. 52-67 to col. 3, lns. 1-35; Formula 2; claim 13).
Berge teaches the list of FDA approved commercially marketed salts in Table 1 and teaches that phosphoric acid salt forms as one of the finite number of FDA approved commercially marketed salt forms to formulate an active pharmaceutical ingredient, and the most preferred. Berge additionally states that several benefits are gained by formulating different active pharmaceutical ingredients into salt form, including chemical, biological, physical and economical properties of the active pharmaceutical agent (pg. 1, col. 1, para. 1; pg. 2, able 1).
Accordingly, one of ordinary skill in the art at the time of the invention would have found it prima facie obvious to formulate the compound (E)-N1-(3-(dimethylamino)propyl)-N8-hydroxy-2-((naphthalen-1-yloxy)methyl)-2-octenediamide, in a phosphoric salt form in view of the teachings of Lee and Berg in order to arrive at the instantly claimed species. One of ordinary skill in the art at the time of the invention would have found it prima facie obvious to employ the pharmaceutically acceptable phosphoric salt (pg. 7, lns. 7-13) to elicit the advantages disclosed by Lee and Berg with a reasonable expectation of success because (1) Lee teaches that the claimed compound can be formulated as a pharmaceutically acceptable salt coupled with the knowledge that (2) the phosphoric acid salt form is one of the most preferred salt species for formulating medicinal compounds due to the corresponding physiological benefits and ease of synthesis as taught by Lee and Berg.
b. Second Rejection
Claim(s) 1, 3-5 and 12 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2007/052938 A1 (Made of Record; hereinafter “Lee”) in view of Berge et al (for Claim 1: hereinafter “Berge”).
With respect to Claim 1, 3-5 and 12, Lee discloses the pharmaceutical composition of the instant claims. As seen on page 3, Formula 1 (pg. 3, lns. 8-23; pg. 8, Compound 1), Lee discloses the pharmaceutical compound of Claim 1. Lee continues to disclose “formulated for oral or parenteral administration. The formulation for oral administration may take various forms such as tablet, pill, soft and hard capsule, solution, suspension, emulsion, syrup, granule and the like…” (pg. 12, lns. 20-23).
And Lee continues to disclose the composition is a tablet or capsule (pg. 12, lns. 20-23) further comprising a coating layer (pg. 13, lns. 1-4), and the coating layer coating layer is present in an amount of 1 to 10%, “at least one of the compounds of formulae 1 to 4 (instant case claims Formula) as an active ingredient in an amount ranging from 0.1 to 75 wt%, preferably 1 to 50 wt% (pg. 12, lns. 17-19), based on the total weight of the composition by weight based on weight of the tablet or capsule (pg. 12, lns. 17-19).
Additionally, Lee discloses (Claims 4, 5 and 12) pharmaceutical composition formulated for injection (sterile injectable formulations; pg. 12, lns. 32-33) is in a liquid (isotonic solution and suspension; pg. 12, lns. 32-33) and a pharmaceutical composition (pg. 3, lns. 28-29 to pg. 4, lns. 1-2) and its use with histone deacetylases (HDACs) teaching “HDAC has been one of targets for the study of anticancer drugs as well as gene expression inhibitors and there have been attempts to develop HDAC inhibitors as anticancer drugs” (pg. 2, lns. 2-4).
Finally, Lee discloses a diC1-3alkylamino, -CH2CH2CH2N(CH3)2 (Example 14: 3-(dimethylamino)propylamine; pg. 48, lns. 27-33 to pg. 49, lns. 1-9) and a general method to make the instant claimed salt species (pg. 7, 14-33 to pg. 8, lns. 1-5).
With respect to the dose ranges of claim 3, Lee teaches overlapping doses at 1 to 10%, (pg. 12, lns. 17-19) in an amount ranging from “0.1 to 75 wt%, preferably 1 to 50 wt%, based on the total weight of the composition”, indicating the remaining percent left in the composition is 25-50% constitute “preservatives, stabilizers, wetting agents, emulsifying agents, osmotic pressure-adjusting agents, buffering agents and the like, and may be formulated through a conventional mixing, granulating or coating procedures” (pg. 12, lns. 23-31).
Even though Lee teaches a general method using the claimed species (pg. 7, 14-33 to pg. 8, lns. 1-5), Lee teaches the free bases of compounds of instant claim 1 as well as compositions and tablet formulations.
Lee fails to teach the phosphate salt with the amine of R1; specifically the claimed species (E)-N1-(3-(dimethylamino)propyl)-N8-hydroxy-2-((naphthalen-1-yloxy)methyl)-2-octenediamide’s phosphoric salt form.
Berge teaches the list of FDA approved commercially marketed salts in Table 1 and teaches that phosphoric acid salt forms as one of the finite number of FDA approved commercially marketed salt forms to formulate an active pharmaceutical ingredient, and the most preferred. Berge additionally states that several benefits are gained by formulating different active pharmaceutical ingredients into salt form, including chemical, biological, physical and economical properties of the active pharmaceutical agent (pg. 1, col. 1, para. 1; pg. 2, able 1).
Accordingly, one of ordinary skill in the art at the time of the invention would have found it obvious to formulate the compound (E)-N1-(3-(dimethylamino)propyl)-N8-hydroxy-2-((naphthalen-1-yloxy)methyl)-2-octenediamide, in a phosphoric salt form in view of the teachings of Lee and Berg in order to arrive at the instantly claimed species.
One of ordinary skill in the art at the time of the invention would have found it obvious to employ the pharmaceutically acceptable phosphoric salt (pg. 7, lns. 7-13) to elicit the advantages disclosed by Lee and Berg with a reasonable expectation of success because (1) Lee teaches that the claimed compound can be formulated as a pharmaceutically acceptable salt coupled with the knowledge that (2) the phosphoric acid salt form is one of the most preferred salt species for formulating medicinal compounds due to the corresponding physiological benefits and ease of synthesis as taught by Lee and Berg.
c. Third Rejection
Claim(s) 1, 3-5 and 12 are rejected under 35 U.S.C. 103 as being obvious by US 8,053,435 B2 (Made of Record; hereinafter “Lee”) in view of Na Y-S et al. (Oncology reports 2010 1509-1514) and Fasinu P et al. (Drug Dispos. 2011 32, 185-209).
Lee discloses an alkylcarbamoyl naphthalenyloxyoctenoyl hydroxyamide derivative of (E)-N1-(3-(dimethylamino)propyl)-N8-hydroxy-2-((naphthalen-1-yloxy)methyl)octenediamide (page 5), which is the compound of Instant Claim 1 (col. 156, ln. 35-36). Lee taught the alkylcarbamoyl naphthalenyloxyoctenoyl hydroxyamides may be used in the form of a pharmaceutically acceptable addition salt, wherein the salt is a phosphoric acid salt (col. 4, lns. 1-13; col. 8, lns. 48-56; col. 25, lns. 13-19).
Lee fails to disclose an embodiment of the phosphoric acid form of Ivaltinostat. The free-base form and salt form (Ivaltinostat phosphate) are equally referred to as Ivaltinostat (as referenced by Drug Bank).
Though the reasoning behind using the salt moiety is known in the art, Fasinu discloses phosphate salt moieties are a conventional approach to enhance solubility properties (page 188, left column, first bullet of last paragraph).
It would have been obvious for a person having ordinary skill in the art to take the method of Lee above – and: use the HDAC inhibitor as the pharmaceutically acceptable phosphoric acid salt form of (E)-N1-(3-( dimethylamino)propyl)-N8-hydroxy-2-((naphthalen-1-yloxy)methyl), which is (E)-Nl-(3-(dimethylamino)propyl)N8-hydroxy-2-((naphthalene-1-yloxy)methyl)-2-octenediamide phosphate as disclosed by Lee and combine it with Fasinu. This is obvious because: 1) Lee taught the alkylcarbamoyl naphthalenyloxyoctenoyl hydroxyamides may be used in the form of a pharmaceutically acceptable addition salt, wherein the salt is a phosphoric acid salt.
Further, a recitation of the intended use of the claimed invention must result in a structural between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
According to the MPEP § 2144.08, subsection II.A.4.(c):
The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein).
Conclusion
Claims 1, 3-5 and 12 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Josmalen M. Ramos-Lewis whose telephone number is (571)272-0084. The examiner can normally be reached M-F 9:30-5:30 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A. Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Josmalen M. Ramos-Lewis, Ph.D.
Patent Examiner
Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
Prosecution Insights