Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/19/2025 has been entered.
Claim Status
Claims 3-14, 16-18, and 20 are pending.
Claims 1-2, 15 and 19 are cancelled.
Claims 11-12 are withdrawn as being directed to a non-elected species, the election having been made on 3/13/2023. The examiner found claim scope of claim 18 overlapping with claim 20; thus, claim 18 is rejoined.
Claims 1-10, 13-14, 16-18, and 20 have been examined.
Priority
This application is a CON of 16/133,185 09/17/2018 PAT 11135230
16/133,185 is a CON of 15/283,971 10/03/2016 PAT 10076530
15/283,971 is a CON of 14/498,548 09/26/2014 PAT 9458409
14/498,548 is a CON of 13/601,626 08/31/2012 PAT 8846604
13/601,626 has PRO 61/650,206 05/22/2012
13/601,626 has PRO 61/530,648 09/02/2011
The limitations of 1-lysophosphatidylcholine and 2-lysophosphatidylcholine is first disclosed in 13/601,626; thus, the prior art date of this application is the effective filing date of 13/601,626 on 08/31/2012.
Modified Rejection
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 3-10, 13-14, 16-18, and 20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The specification failed to provide a representative lipid composition to support the entire genus of a lipid composition comprising “an amount of 1-lysophosphatidylcholine in an amount of 1.7~6.9 mg/g and 15~25.5 mg/g of 2-lysophosphatidylcholine” to dry eye disease in claim 3 underlined sentence as follows.
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The specification of Table 4-1 disclosed 1.7~6.9 mg/g of 1-lysophosphatidylcholine and 15~25.5 mg/g of 2-lysophosphatidylcholine in three extracted phospholipid (PL) comprising minimal 50% phospholipid (PL) ranged from 51.4% to 58.1% by weight and a fish oil carrier; thus, the specification is insufficient to support the entire genus of the claims.
The specification failed to establish correlation of “an amount of 1 lysophosphatidyl-choline in an amount 1.7 mg/g to about 6.9 mg/g (w/w) and 2-lysophosphatidylcholine in an amount of about 15 mg/g to 25.5 mg/g (w/w)” to treat dry eye disease.
Because the specification failed to satisfy the written description requirements (i) and (ii) described above, claims 3-10, 13-14, 16-18, and 20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
Response to Arguments
Applicant's arguments filed 4/21/2025 have been fully considered but they are not persuasive because the arguments are not apply to the modified rejection.
Modified Rejection
Claim Rejections - 35 USC § 112
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 3-10, 13-14, 16-18, and 20 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.
Claims 3 is unclear with respect to (i) missing unit of the ratio DHA to EPA at 1.5:1 (claim 3, para 3) and (ii) the phrase “approximately daily” can be interpreted as administration frequency every 12 hours, every day (every 24 hours), or every 30 hours, rendering the metes and bounds of the phrase indefinite. MPEP 2173.02 (I) states “During examination, after applying the broadest reasonable interpretation to the claim, if the metes and bounds of the claimed invention are not clear, the claim is indefinite and should be rejected. Zletz, 893 F.2d at 322, 13 USPQ2d at 1322. For example, if the language of a claim, given its broadest reasonable interpretation, is such that a person of ordinary skill in the relevant art would read it with more than one reasonable interpretation, then a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph is appropriate.” Claims 4-10, 13-14, 16-18, and 20 are rejected as depending on claim 3.
With respect to claims 7-8 and 18, the units are missing from the ratio of claimed compounds rendering the metes and bounds of the claims indefinite.
Response to Arguments
Applicant's arguments filed 4/21/2025 have been fully considered but they are not persuasive because the arguments are not apply to the modified rejection.
New Ground of Rejection
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
1. Claims 3, 5-10, 13-14, and 16-17 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Sampalis et al. (US 2011/0160161 A1, previously cited 9/25/2023) and evidenced by (i) Monakhova et al. (Analytical Letters. 2018; 51(16): 2551–2562.) and evidenced by (ii) Hallaraker et al. (US 2013/0059768 A1).
Claim 1 is drawn to a method for treating dry eye or an inflammatory disease via oral administration of a composition comprising (A) phospholipids extracted from immature herring roe and (B) a carrier oil; wherein
(i) extracted phospholipids comprise at least about 75 wt.% phosphatidylcholine; at least about 40% of the total fatty acid moieties of the extracted phospholipids are docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), (ii) the ratio of DHA to EPA of the extracted phospholipids is at least about 1.5:1; (iii) an amount of the DHA is about 190 mg/g (w/w) and an amount of the EPA is about 70 mg/g (w/w) of the total amount of the lipid composition.
the lipid composition comprises about 20 wt.% to about 90 wt.% phospholipids and about 10 wt.% to about 80 wt.% carrier oil of fish oil triglyceride
wherein an amount of 1-lysophosphatidylcholine is present in an amount of about 1.7 mg/g to about 6.9 mg/g (w/w) and an amount of 2-lysophosphatidylcholine is present in an amount of about 15 mg/g to about 25.5 mg/g (w/w) of a total amount of phospholipids of the lipid composition; and
wherein administration is approximately daily for an effective amount of time to reduce the severity of the dry eye or the inflammatory disease of the eye.
Sampalis et al. teach administering an effective amount of a concentrated therapeutic phospholipid composition to treat inflammation (Abstract). Sampalis et al. teach the treated inflammatory diseases of the eye including corneal dystrophy, trachoma, onchocerciasis, uveitis, sympathetic ophthalmitis and endophthalmitis [0053]. Sampalis et al. suggest oral administration of the concentrated therapeutic phospholipid composition [0130]. Sampalis et al. teach the source of isolated phospholipids is not critical and can be obtained from various marine organisms such
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as squid, fish, krill, etc. [0014] as long as the isolated phospholipid comprising sufficient amount of the active ingredient omega-3 phospholipid formula I [0018] comprising DHA and EPA shown as follows [0018, 0025-0029]. Sampalis et al. further teach the phospholipid composition further comprising a pharmaceutically acceptable carrier of triglyceride [0132]. When R1 = H and R2=DHA or EPA reads on 1-lysophosphatidylcholine and R2 = H and R1=DHA or EPA reads on 2-lysophosphatidylcholine. Monakhova et al. is cited as evidence to show purified phospholipids from Krill comprising 1-Lysohosphatidylcholine and 2-Lysohosphatidylcholine shown as follows (p2553, Table 1).
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Hallaraker et al. is further cited as evidence to show phospholipid of DHA and EPA can be isolated from fish and immature fish roe of herring, salmon, mackerel, menhaden roe, or a combination thereof known in the art [Abstract; Fig 1-4; 0011], consistent with Sampalis’s teaching that the various sources of marine organisms can provide same DHA and EPA [0014] to treat a patient in need.
With respect to the limitation (a)(i), Sampalis et al. teach the concentrated therapeutic phospholipid composition are in a concentration of above 70% w/w (phospholipids/total composition) to about 99% w/w(phospholipids/total composition) of the compound formula I [0024, claim 7]. Sampalis et al. teach the therapeutic phospholipids comprising an omega-3 phospholipid of lysophosphatidylcholine shown in the compound formula (I) [0018-0021, 0026-0027], reading on 70%-99% of phosphatidylcholine.
With respect to the limitation (a)(ii), Sampalis et al. further suggest the ratio of DHA to EPA is between about 1:1 and 1:0.1 (10:1) [0032]. Although claim 3 has a limitation of “phospholipid extracted from immature herring roe”, there is no evidence that the active ingredients of phospholipids DHA and EPA extracted from krill shown in the structure above are different from phospholipids DHA and EPA extracted from immature herring roe.
With respect to the limitation (a)(iii), an effective amount of phospholipids DHA and EPA is NOT equal to the amount of extracted of phospholipids DHA and EPA with respect to a large amount of carrier oil up to 80% by weight. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See MPEP 2144.05. Obviousness of Similar and Overlapping Ranges, Amounts, and Proportions.
With respect to the limitation (b), Sampalis et al. the concentrated therapeutic phospholipid composition has a triglyceride concentration between about 0% (w/w) and about 30% (w/w) [0044], reading on 70%, 80%, or 90% phospholipids.
With respect to the limitation (c), Monakhova et al. is cited as evidence to show purified phospholipids from Krill comprising 1-Lysohosphatidylcholine and 2-Lysohosphatidylcholine (p2553, Table 1). There is no evidence that the little amount of 1.7 mg/g to about 6.9 mg/g (w/w) and an amount of 2-lysophosphatidylcholine is present in an amount of about 15 mg/g to about 25.5 mg/g (w/w) is critical to treat inflammatory disease or dry eye.
With respect to the limitation (d), Sampalis et al. teach the phospholipid composition can be administered in a single daily dose [0137].
One of ordinary skill in the art at the time the invention was made would have found it obvious to optimize the effective amount of phospholipids of the compound formula I comprising DHA and EPA to treat an inflammatory diseases of the eye including corneal dystrophy, trachoma, onchocerciasis, uveitis, sympathetic ophthalmitis and endophthalmitis [0053] with reasonable expectation of success described above not repeated here. Monakhova et al. is cited as evidence to show purified phospholipids from Krill comprising 1-Lysohosphatidylcholine and 2-Lysohosphatidylcholine (p2553, Table 1). Hallaraker et al. is further cited as evidence to show phospholipid of DHA and EPA can be isolated from fish and immature fish roe of herring, salmon, mackerel, menhaden roe, or a combination thereof known in the art [Abstract; Fig 1-4; 0011], consistent with Sampalis’s teaching that the various sources of marine organisms can provide same DHA and EPA [0014] to treat a patient in need.
With respect to claim 5, Sampalis et al. teach the treated inflammatory diseases of the eye including corneal dystrophy, trachoma, onchocerciasis, uveitis, sympathetic ophthalmitis and endophthalmitis [0053].
With respect to claim 6, Sampalis et al. suggest the phospholipids comprising an omega-3 phospholipid of lysophosphatidylcholine shown in the compound formula (I) above [0018-0021, 0026-0027].
With respect to claim 7-8, Sampalis et al. suggest the ratio of DHA to EPA is between about 1:1 and 1:0.1 (10:1), including about 2:1 (1:0.5) [0032].
With respect to claim 9, Sampalis et al. suggest the phospholipid composition in combination with zinc [0129].
With respect to claim 10, Sampalis et al. teach administering an effective amount of a concentrated therapeutic phospholipid composition to treat inflammatory and diseases (Abstract), reading on pharmaceutical product.
With respect to claims 13-14, Sampalis et al. teach the weight ratio of phospholipids in the composition between 45%(w/w) ~ 99%(w/w)[0022-0024]. Thus, the carrier oil is estimated to be between 1% to 55% by weight.
With respect to claim 16, Sampalis et al. show a process of making a concentrated phospholipid composition comprising a step of separating krill’s protein residues from DHA and EPA to remove proteins from the isolated phospholipid fraction [Fig 1A, 0142], reading on free of shellfish antigens.
With respect to claim 17, Sampalis et al. teach the concentrated phospholipids are essentially no free fatty acids [0031], reading on less than 1 wt% free fatty acid (if the absolute amount of free fatty acid in Sampalis’s phospholipid is not zero).
Response to Arguments
Applicant's arguments filed 4/21/2025 have been fully considered but they are not persuasive because the arguments are not apply to the new ground of rejection.
2. Claims 3-10, 13-14, 16-18, and 20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Sampalis et al. and evidenced by (i) Monakhova et al. and (ii) Hallaraker et al. as applied to claims 3, 5-10, 13-17 and further in view of Dana et al. (US 2007/0265341 A1) and Harris (Cleve Clin J Med. 2004 Mar;71(3):208-10, 212, 215-8; previously cited 9/25/2023).
Claim 4 is drawn to the treated disease as dry eye and claim 18 is drawn to the composition comprises less than about 0.5% arachidonic acid.
Similarly, Dana et al. teach a method of administering a composition comprising at least one omega-3 fatty acid to treat dry eye [0013, claim 26]. Data et al. teach the omega-3 composition comprising eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or a combination thereof [0054-0055, claim 28]. Data et al. teach arachidonic acid can cause or promote inflammation [0066]; thus, the composition is substantially free of arachidonic acid or linoleic acid [0042, claim 3 and 15]. Because Data et al. teach arachidonic acid can cause or promote inflammation, one of ordinary skill in the art would have found it obvious to beneficially remove the inflammatory mediator of arachidonic acid from Sampalis’s phospholipid composition comprising EPA and DHA for treat inflammatory diseases of eyes, such as dry eye, reading on claims 4 and 18.
Sampalis et al. and evidenced by (i) Monakhova et al. and (ii) Hallaraker et al. in view of Dana et al. do not teach a maximum mercury concentration of about 0.01 mg/kg mercury concentration of about 0.01 mg/kg.
Harris teaches fish oil supplementation (Title). Harris suggests fish oil capsules or other omega-3 oil of animals (p210, Table 1) containing no mercury can be made by oil extraction processes because the toxic methyl mercury is water-soluble not oil-soluble (p217, col 2, Fish oil capsules). Because Harris teaches the beneficial use of oil extraction processes to remove toxic mercury and make an oil composition free of mercury, one of ordinary skill in the art would have found it obvious to use Harris’s oil extraction processes to remove the toxic mercury and produce phospholipid composition containing no mercury, reading on the limitation of a maximum mercury concentration of about 0.01 mg/kg, reading on claim 20.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (A) Sampalis et al. and evidenced by (i) Monakhova et al. and (ii) Hallaraker et al. and (B) Dana et al. because (1) Sampalis et al. teach administration of omega-3 fatty acid as an anti-inflammatory agent [0012] comprising phospholipids compound formula I of EPA and DHA [0018, 0025-0029] to treat inflammatory diseases of the eye [0053] and (2) Data et al. teach arachidonic acid can cause or promote inflammation [0066]; thus, the composition is substantially free of arachidonic acid or linoleic acid [0042, claim 3 and 15]. The combination would have reasonable expectation of success because both Sampalis et al. and Dana et al. teach administration of a composition comprising EPA and DHA to treat inflammatory diseases of the eye.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (A) Sampalis et al. and evidenced by (i) Monakhova et al. and (ii) Hallaraker et al. in view of Dana et al. and (B) Harris because (1) Sampalis et al. and evidenced by (i) Monakhova et al. and (ii) Hallaraker et al. in view of Dana et al. teach administration of a phospholipid composition comprising EPA and DHA substantially free of arachidonic acid to treat inflammatory diseases of the eye including dry eye and (2) Harris teaches omega-3 oil (p210, Table 1) containing no mercury can be made by oil extraction processes because the toxic methyl mercury is water-soluble not oil-soluble (p217, col 2, Fish oil capsules). The combination would have reasonable expectation of success because both Sampalis et al. (Fig 1A step 4) and Harris teach the use of water in a process of isolating omega-3 phospholipid comprising EPA and DHA.
Response to Arguments
Applicant's arguments filed 4/21/2025 have been fully considered but they are not persuasive because the arguments are not apply to the new ground of rejection.
Conclusion
No claim is allowed.
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/J.L/Examiner, Art Unit 1658
28-November-2025
/LI N KOMATSU/ Primary Examiner, Art Unit 1658