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
Response to Amendment
Acknowledgment is made of the receipt and entry of the amendment filed on 03/18/2026, wherein claim 22 is cancelled, claim 21 is amended to recite compound of formula IIA without definition of R5 and R7, and claim 23 is amended to recite a specific structure,
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. Instant specification does not explicitly disclose compound of claim 23 with the specific geometric stereochemistry. As necessitated by amendment, claims 21, 23 and 24 are newly rejected under 35 USC 112.
Election/Restriction
Applicant elected without traverse of Group I, claims 21-24 and species of synaptamide phosphonate on 09/12/2024.
Instant specification does not disclose IUPAC name of synaptamide phosphonate or specify the position(s) of double bonds of docosahexaenoic acid and geometric stereochemistry thereof. It’s noted docosahexaenoic acid (22:6) might comprise various regional and cis/trans(Z/E) isomers of the six double bonds. Different DHA isomer(s) comprising different cis or trans double bonds at different locations would have different steric conformation that impact on the activity of its aminoethyl phosphonate derivative with biomarkers. The most common DHA is all-cis-docosa-4,7,10,13,16,19-hexaenoic acid with six cis-double bonds at positions 4, 7, 10, 13, 16 and 19. According to STN structure search, compound of Formula IIA comprising all Z isomers 4Z,7Z,10Z,13Z,16Z,19Z as drawn in claim 23 was not entered into STN database.
Status of Claims
Claims 21 and 23-32 are pending in the instant application.
Claims 25-32 remain withdrawn.
Claims 21 and 23-24 are currently under examination.
Response to Arguments
Applicant's Remarks filed 03/18/2026 have been fully considered. Any objection and rejection found in the previous Office Action and not repeated herein has been withdrawn in view of amendment and Applicant’s remarks. The text of those sections of Title 35 U.S. Code not included in this action can be found in a prior Office action.
Applicant's argument have been fully considered, but NOT persuasive to overcome rejections of claims 21, 23 and 24 as being unpatentable over Lynch in view of Strelchenok under 35 USC 113.
Applicant argues different design rationale of Lynch, and there is no suggestion in Lynch to shorten the chain connecting the nitrogen to the phosphorus... (Remarks, page 10-11/13).
RESPONSE: Please note instant claims are compound claims wherein the biological activity is the property of the compound which does not necessarily further contribute to the structural limitation of the compound. A claimed compound may be obvious because it was suggested by, or structurally similar to, a prior art compound even though a particular benefit of the claimed compound asserted by patentee is not expressly disclosed in the prior art. It is the differences in fact in their respective properties which are determinative of non-obviousness. Lynch’ 001 does not only teach phosphonate target at LPA receptor, Lynch’ 001 also teaches LPA receptor agonists can improve neuronal function or enhance immune response for treating Alzheimer disease , Parkinson's disease. (See page 31, lines 30-32; page 34, line 13-15).
Lynch’ 001 collectively teaches phosphonates comprising various fatty acid acyl amide , preferably R1 is 15:0, 17:0, 17:1, 19:4 or 21:6 hydrocarbon, that are homolog of instant claimed compound formula IIA, Please note 21:6 acyl read on instantly claimed docosahexaenoic acid (22:6, DHA). Lynch’ 001 explicitly teaches wls-b8L, homolog of instant compound of Formula IIA wherein R5 is oleic acid and activity thereof. Please note prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979).
Applicant argues phosphonate moieties can change the activity of LPAs when replacing the phosphate in a negative direction... Applicants' invention where synaptamide phosphonate had markedly better activity than synaptamide phosphate (Remarks, page 11/13).
RESPONSE: Please note Lynch’ 001 already teaches phosphonate embodiment comprising docosahexaenoic acid (22:6) moiety which is only one carbon shorter than instant claimed synaptamide phosphonate. The modification is based on Lynch’ 001 phosphonate embodiment comprising docosahexaenoic acid (22:6) moiety, not to replace the Strelchenok's phosphate . Strelchenok's teaching is to show that N-docosahexaenoyl-O-phospho-2-aminoethanol (C6) is already known compound. Lynch’ 001 teaches the purpose of phosphonate is resistant to hydrolysis by phosphohydrolases than a phosphate group (See page 31, line 15-16; page 24, line 10). A POSA would have known to keep the phosphonate group to prevent hydrolysis by phosphohydrolases based on Lynch’ 001 teaching and general knowledge of fatty acid/phospholipid. Further, instant specification does not explicitly disclose the structure of synaptamide phosphonate or synaptamide phosphate with specified position(s) of double bonds and geometric stereochemistry thereof that are associated with the alleged activity.
Priority
This application 17/432,510 filed on 08/20/2021, is a 371 of PCT/EP2020/054662 filed 02/21/2020 which claims benefit of EP 19305212.3 filed 02/21/2019 and EP 19306376.5 filed 10/23/2019.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy of foreign Application No. 19305212.3 and EP 19306376.5 were filed on 08/20/2021 according to the record.
Claim Rejections - 35 USC § 112
Necessitated by Amendment
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 21, 23 and 24 are rejected under 35 U.S.C. 112(a), 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 21 is amended to recite Formula IIA without definition of R5 and R7 groups, “which is synaptamide phosphonate” and the hydrates, the diastereomers, or salt thereof. Please note “synaptamide phosphonate” is NOT IUPAC name or a widely-used common name. Instant specification does not explicitly disclose the structure of synaptamide phosphonate is a compound of Formula IIA with specific definition of isomers. It’s noted docosahexaenoic acid (22:6 n-3 ) might comprise various regional and cis/trans(Z/E) isomers of the six double bonds. Different DHA isomer(s) comprising different cis or trans double bonds at different locations would have different steric conformation that impact on the activity of its aminoethyl phosphonate derivative with biomarkers. An ordinary skilled in the art would not know what’s the exact structure of instant claimed synaptamide phosphonate as one isomer or as a mixture of different isomers that’s associated with the activity . As such, claim 21 reciting Formula IIA in absence of definition of R5 and R7 and synaptamide phosphonate lacks sufficient support by instant disclosure. More importantly, instant specification(See [0328]-[0332]) disclosed synaptamide phosphonate, synaptamide phosphate and synaptamide are metabolic derivatives of docosahexaenoic acid (DHA). Although instant specification ([0419]) disclosed synaptamide phosphonate as synaptamide derivative has never been characterized, an ordinary skilled in the art would not know if instantly synthesized synaptamide phosphonate without specified structure is the same or different from naturally occurred metabolic synaptamide phosphonate which would not be patentable subject matter under 35 USC 101. Applicant is required to provide evidence that instantly claimed/synthesized synaptamide phosphonate and compound of claim 23 is different from naturally occurred metabolic synaptamide phosphonate.
Claim 23 is amended to recite a specific structure with defined geometric all-cis Z isomer,
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Instant specification discloses ethanolamine-phosphonate derivatives compound of Formula IIA(See [0270]-[0274]), wherein R5 represents a saturated or unsaturated fatty acyl comprising from 2 to 30 carbon atoms and preferred embodiments chosen from capric acid, eicosapentaenoic acid, and docosahexaenoic acid. Instant specification (See [0364]) disclosed synthesis of synaptamide phosphonate starting from docosahexaenoic acid/DHA characterized by mass spectrometry. Although natural form of docosahexaenoic acid/DHA comprises primarily all-cis (4Z,7Z,10Z,13Z,16Z,19Z)-DHA, docosahexaenoic acid/DHA also comprise various regio-isomers and geometrical isomers and might generate more trans isomers during the process of preparing synaptamide phosphonate. Please note cis-isomer and trans-isomer have different biological activity. Instant specification does not explicitly disclose the specific chemical structure comprising all Z isomers as recited in claim 23. Instant specification does not disclose IUPAC name of synaptamide phosphonate or specify the position(s) of double bonds and geometric stereochemistry thereof as the specific structure in claim 23. As such, instantly claimed compound of claim 23 with the specific geometric stereochemistry lacks sufficient support by instant specification.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 21 and 24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 21 is amended to recite Formula IIA “which is synaptamide phosphonate” and the hydrates, the diastereoisomers, or salt thereof, without definition of R5 and R7 groups. Please note “synaptamide phosphonate” is NOT IUPAC name or a widely-used common name. Instant specification does not explicitly disclose synaptamide phosphonate is a compound of Formula IIA. An ordinary skilled in the art would not know how synaptamide phosphonate is related to compound of IIA and what R5 and R7 are defined in synaptamide phosphonate.
Claim 24 is also rejected due to dependency on claim 21.
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 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 non-obviousness.
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 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 21, and 23- 24 are rejected under 35 U.S.C. 103 as being unpatentable over Lynch et al. (WO 02/29001, hereafter Lynch ‘001), in view of Strelchenok et al (WO 02/04467 A1, Applicant’s IDS dated 01/05/2022).
Lynch’ 001 discloses lysophosphatidic acid (LPA) analogs, wherein glycerol is replaced with ethanolamine, as agonist or antagonists of LPA receptor which can be used to inhibit LPA mediated activities and thus treat disorders of abnormal cell growth and differentiation as well as inflammatory diseases (e.g. Alzheimer’s disease, etc. )(See abstract; page 12, lines 1-8, 16-17, 29-31; page 40, lines 5-12; claims 1-3, 10-12, 21-22).
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Lynch ’001 teaches LPA analogs embodiments comprising phosphonate, compound of Formula IV, V, etc. (See page 27, 28, lines 5-30; page 29, lines 5-31; page 34, lines 1-9; claims 21, 22, 29)
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Lynch ‘001 teaches preferably R1 is a 15:0, 17:0, 17:1, 19:4 or 21:6 hydrocarbon, wherein 21:6 acyl read on instantly claimed docosahexaenoic acid (22:6 n-3, DHA), 15:0 acyl is palmitic acid, 17:1 acyl is oleic acid, etc.(See page 12, lines 29-31; page 13, lines 4; page 28, line 24-25). Lynch’ 150 explicitly teaches compound species comprising oleoyl amide(18:1), e.g. wls-b8L ( See page 31, lines 10-20; claim 11; page 37, lines 15-21; page 31, lines 6-16; Example 5).
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Lynch’ 001 collectively teaches phosphonates comprising various fatty acid acyl amide , preferably R1 is 15:0, 17:0, 17:1, 19:4 or 21:6 hydrocarbon, that are homolog of instant claimed compound formula IIA. According to M.P.E.P. § 2144.09, A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." “Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious”. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979). (Claimed and prior art compounds were both directed to heterocyclic carbamoyloximino compounds having pesticidal activity. The only structural difference between the claimed and prior art compounds was that the ring structures of the claimed compounds had two carbon atoms between two sulfur atoms whereas the prior art ring structures had either one or three carbon atoms between two sulfur atoms. The court held that although the prior art compounds were not true homologs or isomers of the claimed compounds, the similarity between the chemical structures and properties is sufficiently close that one of ordinary skill in the art would have been motivated to make the claimed compounds in searching for new pesticides).
Strelchenok teaches phosphate comprising amides of polyunsaturated fatty acids which exhibit
cell-growth inhibiting effect and anti-tumour activity, wherein polyunsaturated fatty acids (PUFAs) may sensitize tumour cells to anti-cancer drugs in cell and interfere with tumour cell proliferation in vitro and in vivo due to the formation of oxidation products (See abstract, page 1, lines 12-26).
Strelchenok explicitly teaches N-docosahexaenoyl-O-phospho-2-aminoethanol (C6), N- eicosapentaenoyl-O-phospho-2-aminoethanol(C7), N-arachidonoyl-O-phospho-2-aminoethanol, N- a- linolenoyl O-phospho-2-aminoethanol, and N- γ-linolenoyl O-phospho-2-aminoethanol( See abstract, page 3, lines 15-28; page 4, lines 25-29, compounds C6-C10; Example 7 and 8 on page 12). It’s noted N-docosahexaenoyl-O-phospho-2-aminoethanol (C6) where acyl is cis-4,7,10,13,16,19-docosahexaenoyl (CAS # 286431-52-5) having following structure is very similar to instantly claimed formula IIA, except phosphate vs phosphonate.
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It would be obvious for an ordinary skilled in the art before the effective filing date of instant invention to incorporate polyunsaturated fatty acyl amides (e.g. docosahexaenoyl ethanolamide) taught by Strelchenok as the C8-C22 alkenyl/alkyl of R1 acyl group in phosphonate LPA analogs taught by Lynch ’001, together with experimentation/optimization based on general knowledge of fatty acid/phospholipid, and arrive at instantly claimed invention with reasonable expectation of success. A skilled artisan would be motivated to combine the teachings of Lynch ’001 and Strelchenok because both are directed to phospholipids (phosphate and phosphonate) comprising long chain fatty acyl amide . According to M.P.E.P. § 2144.09, A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art, together with exploration/ optimization based general knowledge of fatty acid and phospholipids. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
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 21, and 23-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of copending Application No. 19/638,374 (reference application). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Although the claims at issue are not identical, they are not patentably distinct from each other.
Reference claims are directed to a compound of formula (IIA) which reads on instant claimed formula (IIA).
Reference claim 2 and 3 recite R5 has 22 carbon atom and/or docosahexaenoic acid.
Reference claim 4 recites the compound, diastereomer of all- trans isomer of instant claim 23.
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Reference claim 5 recites synaptamide phosphonate
Reference claims anticipate or essentially overlap with instant claims.
According to M.P.E.P. § 2144.09, A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
Reference application is continuation of instant application and no 35 USC 121 shield exists.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/L.M./Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
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