Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-20 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/21/26 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn rejections
Applicant's amendments and arguments filed 7/27/26 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below is herein withdrawn.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Claim Rejections - 35 USC § 103
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-4, 9-14, 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Buchman et al. (US5567736; of record) and Barranco Perez et al. (EP2859889).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, 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 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims, for example:
PNG
media_image1.png
176
1036
media_image1.png
Greyscale
Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a parenteral nutrition (PN) artisan who recognizes choline as an essential nutrient for long-term PN patients, which is essential for preventing hepatic steatosis (fatty liver) and liver dysfunction.1 They know that standard PN solutions are often choline-deficient, causing low plasma choline levels, and that supplementation is crucial for maintaining liver health, methyl metabolism, and membrane structure. Such an artisan will employ conventional ingredients and formulations known in the art.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1, 4 and 11, Buchman et al. teach methods of administering a choline salt to inhibit fatty liver in patients receiving total parenteral nutrition to maintain plasma free choline levels within normal limits (Title; Abstract; claim 1). Buchman et al. teach: “choline chloride or other choline salt is added to the nutrient solution in an amount sufficient to provide from 0.25 to about 8 grams of choline per liter of solution.” (Column 2, lines 20-26; claim 2). That overlaps the claimed range of from 0.01 g to 15.0 g per liter and renders the range obvious. See MPEP 2144.05(I): In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
Total daily dosage is about 0.5 to 8 grams of choline (Column 4, lines 33-37). Administration was done intravenously with lipid emulsions (Intralipid 20%) (Column 1, lines 42-51; column 4, lines 53-55; column 6, lines 24-25; column 7, lines 1-2). Intralipid 20% is within the claimed range of about 5 to about 35% by weight of an oil phase.
Regarding claims 9 and 19, Buchman et al. teach: “Administration of the nutrient solution is generally accomplished by way of a central venous catheter which is inserted in the superior vena cava.” (Column 1, lines 49-51). Hence, a centrally inserted catheter.
Regarding claims 10 and 20, Buchman et al. do not add eicosapentaenoic acid (EPA) and the limitation of the composition being essentially free of EPA is defined in the specification as being no more than 0.001% [0055], which means the range encompasses all values between 0 and 0.001. Thus, the composition of Buchman et al. is essentially free of EPA.
Regarding claims 1 and 11, Barranco Perez et al. teach a nutritional composition comprising a source of choline in an amount sufficient to provide 0.4 to 8 grams of choline per day (claim 1) where the choline is glycerophosphocholine (Claims 3-4). Barranoc Perez et al. teach aqueous emulsions, water-in-oil emulsions and oil-in-water emulsions [0055].
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and Buchman et al. is that Buchman et al. do not expressly teach glycerophosphocholine in an administered dose of from 15 mg/kg/day to 300 mg/kg/day or a dose of from 50 mg/kg/day to 150 mg/kg/day in a pediatric patient. This deficiency in Buchman et al. is cured by the teachings of Barranco Perez et al.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ glycerophosphocholine, as suggested by Barranco Perez et al., in an administered dose of from 15 mg/kg/day to 300 mg/kg/day or a dose of from 50 mg/kg/day to 150 mg/kg/day in a pediatric patient in the method of Buchman et al. and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because: 1) Buchman et al. is not limited to choline and contemplates other sources of choline: “other choline salts…may be used. In addition, choline precursors and choline metabolites such as phosphatidyl choline, CDP-choline, soy lecithin, etc., may be used.” (Column 3, lines 38-43); and 2) Barranco Perez et al. render obvious choline and glycerophosphocholine as familiar functional equivalents to provide a source for choline. "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007). Moreover, “Where two known alternatives are interchangeable for a desired function, an express suggestion to substitute one for the other is not needed to render a substitution obvious." In re Fout 675 F.2d 297, 301 (CCPA 1982). Thus, it would be obvious to use glycerophosphocholine in the method of Buchman et al. The method of Buchman et al. includes all patients (See column 7, lines 1-3: “also contemplates the administration of choline intravenously to treat a variety of patients who are suffering from choline deficiency.”), which includes adult and pediatric patients. The ordinary artisan would treat pediatric patients with a reasonable expectation of success. Regarding the claimed dosage ranges, not only does Buchman et al. teach dose adjustment (Column 5, line 67) but also it is merely routine optimization by the ordinary artisan to arrive at the claimed dosages of from 15 mg/kg/day to 300 mg/kg/day or a dose of from 50 mg/kg/day to 150 mg/kg/day with a reasonable expectation of success. Pharmaceutical dose has been recognized as a result-effective parameter susceptible to routine optimization. See, e.g., Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 809 (Fed. Cir. 1989). See also MPEP 2144.05 (II) (A): “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Thus, the ordinary artisan would adjust the dose based on the patient’s condition(s), where, for example, an adult would weigh more than a child, to achieve the desired result of obtaining at least a normal level of choline in the patient with a reasonable expectation of success. Especially when the prior art teaches an overlapping concentration of about 0.25 to about 8 grams of choline per liter of solution administered per day. Consequently, an administered dose of from 15 mg/kg/day to 300 mg/kg/day or a dose of from 50 mg/kg/day to 150 mg/kg/day in an adult or pediatric patient is obvious in view of the combined references. Furthermore, a peripheral or centrally inserted catheter would be at the discretion of the ordinary artisan practicing the method of Buchman et al.
Claims 5-8 and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over Buchman et al. (US5567736; of record) and Barranco Perez et al. (EP2859889), as applied to claims 1-4, 9-14, 19 and 20 above, in further view of Hoffman et al. (WO2011097273; of record) and Yoshio Shimizu (JPH05163142A; English translation provided by the Examiner).
Applicant claims, for example:
PNG
media_image2.png
522
1032
media_image2.png
Greyscale
The references of Buchman et al. and Barranco Perez et al. are discussed in detail above and that discussion is incorporated by reference.
Regarding claims 1, 5-8, 10-11, 15-18 and 20, Hoffman et al. teach methods of treating fatty liver disease/liver damage by administering to a subject a composition comprising about 200 mg to about 12 g of DHA and is substantially free of EPA (Abstract; [0002, 0013, 0017-0018, 0092, 0094]; claims 1, 58, 69-71) where EPA is less than 3%, 1%, 01% wt/wt of the dosage form (Claims 8-9). The dosage form can comprise from 0.01% to 0.5% wt/wt arachidonic acid [0058] or arachidonic acid can be present from less than about 2% wt/wt (Claims 13, 31, 62).
Regarding claims 1, 7-8, 11 and 17-18, Shimizu teaches an arachidonic containing composition for preventing and treating hepatic diseases/liver damage comprising ≥ 2 wt% arachidonic acid (Abstract; claim 1). Shimizu teaches compositions with 2% by weight or more, preferably 10% by weight arachidonic acid [0004] as well as parenteral administration [0010].
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and Buchman et al. as modified by Barranco Perez et al. is that Buchman et al. as modified by Barranco Perez et al. do not expressly teach adding from 0.1g to 50.0 g per 100 g of the oil phase DHA or adding from 0.1 g to 15.0 g per 100 g of the oil phase ARA. This deficiency in Buchman et al. as modified by Barranco Perez et al. is cured by the teachings of Hoffman et al. and Shimizu.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add from 0.1g to 50.0 g per 100 g of the oil phase DHA or adding from 0.1 g to 15.0 g per 100 g of the oil phase ARA, as suggested by Hoffman et al. and Shimizu, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because the references are directed to treating liver disease/damage and guide the artisan to using DHA and ARA where Hoffman et al. teach 200 mg to about 12 g of DHA and less than about 2% wt/wt ARA and Shimizu teach using more than 2 wt% ARA. Consequently, it is merely routine optimization to add from 0.1g to 50.0 g per 100 g of the oil phase DHA or adding from 0.1 g to 15.0 g per 100 g of the oil phase ARA to the oil phase of the lipid emulsion of Buchman et al. as modified by Barranco Perez et al. with a reasonable expectation of success. The Examiner points out that 0.1 g per 100 g of the oil is 0.1%.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Response to Arguments:
Applicant’s arguments filed 7/27/26 have been carefully considered but are not persuasive.
On page 6 of remarks, Applicant asserts: “Buchman also fails to disclose or suggest "a lipid emulsion" containing the alleged choline.” Applicant contends that Intralipid was a caloric supplement separately co-administered as part of the subject’s overall TPN regimen and was not a vehicle into which the choline was incorporated. Respectfully, the Examiner has a different perspective. As noted in the rejection, Buchman teaches the use of Intralipid 20% for intravenous injection (Column 4, lines 53-54) and notes early morning headaches associated with the lipid emulsion (Column 6, lines 23-25). The only reasonable conclusion is that Buchman teach and suggest lipid emulsion administration. Buchman teaches that the subjects received their TPN nightly as one dose (Column 4, lines 60-62) and not separate doses. Buchman does not teach a separate dose of Intralipid and a separate dose of TPN. Intralipid makes up the TPN and only one dose of TPN is administered. In other words, Intralipid is part of the TPN which is administered in a single dose with the choline/choline source. Buchman also teach that the choline is administered using a pharmaceutically suitable carrier (Column 7, lines 3-6) and Intralipid is a pharmaceutically suitable carrier. Thus, it is reasonable to conclude that the choline/choline source is incorporated into the lipid emulsion TPN solution as a single TPN dose for administration. Respectfully, Applicant’s arguments are not persuasive. As an additional comment, the Examiner notes that Intralipid 20% is intended for use in preparation of three-in-one total nutrient admixtures and not intended for direct infusion.2 The ordinary artisan utilizing Intralipid 20% would know this conventional knowledge and have it admixed with the TPN and the choline/choline source.
The secondary references are relied upon as applied in the rejection.
On page 7 of remarks, Applicant asserts that Buchman has no teaching regarding the stability, compatibility or behavior of any choline compound, let alone glycerophosphocholine, when incorporated into a lipid emulsion. Respectfully, there is no requirement that Buchman provide teachings regarding the stability, compatibility or behavior of any choline compound when incorporated into a lipid emulsion. It is sufficient that Buchman provides guidance on the combination. A prima facie case of obviousness is made by presenting evidence that the "reference teachings would appear to be sufficient for one of ordinary skill in the relevant art having the references before him to make the proposed substitution, combination or other modification." In re Lintner, 458 F.2d 1013, 1016 (CCPA 1972). The test for obviousness is "what the combined teachings of the references would have suggested to those of ordinary skill in the art." In re Keller, 642 F.2d 4I3, 425 (CCPA I98I) (MPEP 2145(III)). In the present case, the combined references render obvious a method of providing choline to a patient who requires parenteral nutrition by parenterally administering a lipid emulsion composition containing glycerophosphocholine with a reasonable expectation of success. (See MPEP 2143.02: The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).) “In the consideration of references, the question is, could one skilled in the art with the references before him make the combination of elements here claimed without exercise of the inventive faculty,” In re Goepfrich, 136 F.2d 918, 920 (C.C.P.A. 1943). In the Examiner’s reasoned analysis with evidentiary support that answer is yes. All that is required to show obviousness is that the applicant "make his claimed invention merely by applying knowledge clearly present in the prior art. Section 103 requires us to presume full knowledge by the inventor of the prior art in the field of his endeavor." In re Winslow, 365 F.2d 1017, 1020, 53 C.C.P.A. 1574, 1578 (1966). Application of Sheckler, 438 F.2d 999, 1001 (C.C.P.A. 1971). Thus, does Applicant make their claimed invention merely by applying knowledge clearly present in the prior art. Under that test, Applicant fails. No commercial success is claimed, nor is any other factor indicating non-obviousness shown to exist. The claims remain rejected.
MPEP 2141 III states: “The proper analysis is whether the claimed invention would have been obvious to one of ordinary skill in the art after consideration of all the facts.” Respectfully, after review of all the facts, Applicant’s arguments are not persuasive. The Examiner has reached a determination that the instant claims are not patentable in view of the preponderance of evidence and consideration of all the facts, which is more convincing than the evidence which has been offered in opposition to it.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-9, 16 and 19-22 of U.S. Patent No. 12171866. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent is directed to:
PNG
media_image3.png
354
566
media_image3.png
Greyscale
Where the composition according to claim 1 of the patent is a lipid emulsion for parenteral administration comprising from 0.1 to 15.0 g per liter of GPC, 0.1 g to 5.0 g per 100 g oil phase DHA and 0.1 g to 15.0 g of the oil phase ARA for use in the treatment of choline deficiency and liver damage and is essentially free of EPA. Claim 8 of the patent is directed to pediatric patients. Claim 16 of the patent teaches the lipid emulsion comprises an aqueous phase and between 5% to about 35% by weight of an oil phase and is used for treating liver damage.
The patent does not expressly teach a method of providing choline to a patient who requires parenteral nutrition for reducing ALT activity. However, that is implicit in the method of the patent because the same components are administered in the same amounts.
The ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the patented subject matter.
Response to Arguments:
Applicant requests that the rejection be withdrawn or held in abeyance. MPEP 804(I)(B)(1) states: “A complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional.” And MPEP 714.03 states: “Where an amendment substantially responds to the rejections, objections, or requirements in a non-final Office action (and is a bona fide attempt to advance the application to final action) but contains a minor deficiency (e.g., fails to treat every rejection, objection, or requirement), the examiner may simply act on the amendment and issue a new (non-final or final) Office action. The new Office action may simply reiterate the rejection”. Accordingly, the double patenting rejection is maintained at this time.
Conclusion
No claims are allowed.
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 ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
1 See Buchman, AL “The Addition of Choline to Parenteral Nutrition” Gastroenterology 2009;137:S119-S128.
2 As evidenced by Intraplipid® 20% [online] retrieved on 8/17/26 from: https:// dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=cbd3396e-6b85-41bf-82d2-940beba86686&type=display; revision 2006; Marketing start date 2004; 10 pages. See pages 1 and 4-5 Dosage and Administration; page 6, Mixing Guidelines and Limitations.
Prosecution Insights