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
This office action is a response to applicant’s communication submitted July 2, 2026, wherein claims 4-6, 20, and 21 are canceled. This application is a continuation of US application 16/289288, now US patent 11234992, filed February 28, 2019, which claims benefit of provisional application 62/636708, filed February 28, 2018.
Claims 1, 8-16, and 22-29 are pending in this application.
Claims 1, 8-16, and 22-29 as amended are examined on the merits herein.
Response to Arguments
Applicant’s amendment, submitted July 2 2026, with respect to the rejection of claims 20 and 21 under 35 USC 103 for being obvious over Vigsnaes et al. as evidenced by Li et al., has been fully considered and found to be persuasive to remove the rejection as claims 20 and 21 have been canceled. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted July 2 2026, with respect to the rejection of claim 5 under 35 USC 103 for being obvious over Vigsnaes et al. in view of Reiche et al., has been fully considered and found to be persuasive to remove the rejection as claim 5 has been canceled. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted July 2 2026, with respect to the rejection of claim 5 under 35 USC 103 for being obvious over Kang et al. in view of Wang et al., has been fully considered and found to be persuasive to remove the rejection as claim 5 has been canceled. Therefore the rejection is withdrawn.
The following new grounds of rejection are introduced:
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 8-13, and 16 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Vigsnaes et al. (PCT international publication WO2019/106620, Reference of record in previous action) as evidenced by Li et al. (Reference of record in previous action)
Independent claims 1 and 8 are directed to a method comprising administering two or three oligosaccharides to a subject, wherein these oligosaccharides are described as being selected from a group including a first listing of neutral oligosaccharides including 2’-fucosyllactose and a second group which is 6’- sialyllactose. Furthermore claim 1 describes the method as a method of treating or attenuating atherosclerosis while claim 8 describes the method as a method of treating or attenuating complications associated with atherosclerosis. Still further the claims require that the effective amount of the active ingredients significantly reduces inflammation caused by macrophages.
Vigsnaes et al. discloses a human milk oligosaccharide for use in increasing the abundance of Akkermansia in the gastrointestinal tract of a human, preferably for treating or preventing one of a number of conditions including metabolic disorders associated with obesity, diabetes, and liver disease. (p. 4 lines 9-14) Human milk oligosaccharides include, for example, a combination of 2’-fucosyllactose and 6’-sialyllactose. (p. 5 lines 8-9) Specific conditions treatable by this method include atherosclerosis. (p. 13 lines 3-16) While Vigsnaes et al. does not specifically state that the therapeutic benefits described in the reference are accomplished by a mechanism involving suppressing inflammation caused by macrophages, Li et al. discloses a study of the effects of Akkermansia muciniphila in a mouse model of atherosclerosis. (p. 2435 left column last paragraph – right column third paragraph) A. muciniphila is specifically mentioned as a beneficial species of Akkermansia in the disclosure of Vigsnaes et al. (p. 2 lines 8-23) Treatment with A. muciniphila probiotic reduced atherosclerotic lesion size. (p. 2436 left column last paragraph – right column third paragraph) Li further discloses that the progression of atherosclerosis is promoted by macrophage-induced inflammation, and that this macrophage induced inflammation was reduced by treatment with A. muciniphila. (p. 2437 right column last paragraph – p. 2438 right column first paragraph) Therefore based on the disclosure of Li et al., it can reasonably be concluded that the beneficial effect of the human milk oligosaccharides described by Vigsnaes et al. for treating atherosclerosis is inherently produced at least in part by the reduction of inflammation caused by macrophages, in view of the fact that Li indicates that the effect of Akkermansia on atherosclerotic lesions is driven at least in part by suppression of macrophage inflammation.
Regarding claim 16, Vigsnaes et al. discloses that the composition can be a nutritional product. (p. 5 line 3) Regarding claim 9, p. 13 lines 3-16 of Vigsnaes further describes treating complications such as stroke and cardiac pathology. Regarding claim 10, as discussed previously, Li indicates that increasing the population of Akkermansia in a subject suffering from atherosclerosis would reasonably be expected to reduce the size of aortic plaques. Regarding claim 11, Vigsnaes describes a pharmaceutical composition comprising one or more excipients. (p. 17 lines 19-22) Regarding claims 12 and 13, Vigsnaes describes orally administering the composition, for example as a tablet. (p. 17 line 29)
For these reasons Vigsnaes et al. anticipates the present claims.
Response to Arguments: Applicant’s arguments, submitted July 2, 2026, with respect to the above ground of rejection, have been fully considered and not found to be persuasive to remove the rejection. Firstly, Applicant argues that Vigsnaes et al. is not prior art against the present claims. Applicant states that the present claims have an effective filing date of February 28, 2018, in accordance with the filing date of provisional application 62/636708. The examiner agrees with this statement. However, Applicant further argues that the priority documents PA201700690 and PA201700680, which Vigsnaes claims priority to, do not provide support for the rejection because they do not teach or suggest reducing atherosclerotic lesions or aortic plaque size, as recited in claim 1 or treating atherosclerosis as recited in claim 8. The priority document PA201700690, filed on December 5, 2017, is included with the present PTO-892. A review of this disclosure indicates that it includes the same statements about the treatment of atherosclerosis cited in the disclosure of Vigsnaes et al. above. Therefore no separate issues are raised by any alleged difference between the disclosure of the published document WO2019/106620 and its foreign priority document PA201700690.
Regarding the disclosure of Vigsnaes et al., Applicant argues that the examiner’s conclusion that administration of HMO as a probiotic to a subject suffering from atherosclerosis so as to increase the abondance of A. muciniphila, is countered by the disclosures of two publications of Pessentheiner et al. As an initial matter, A review of all forms PTO-1449 and PTO-892 of record suggests that these publications are not of record in the present application. it is improper for Applicant to rely upon a published item of non-patent literature as an evidentiary basis for their arguments without making said document of record in the application. In order to correct this, the examiner has located the cited documents and made them of record with the accompanying form PRO-892.
Looking at the actual disclosures of these documents, both documents describe experiments which establish that human milk oligosaccharides attenuate macrophage inflammation, both in cell cultures and when administered subcutaneously to a mouse model of atherosclerosis. Applicant argues that because these results cannot possibly be mediated by a probiotic action on A. muciniphila in the gut, the evidence does not support a conclusion of inherency based on Vigsnaes’ disclosure.
Regarding Applicant’s arguments, the examiner first notes that the above rejection is based on anticipation under 35 USC 102, and not on obviousness under 35 USC 103. Therefore evidence of unexpected results cannot be taken as a basis for overcoming the rejection. Rather, in order to overcome a finding of inherency, proffered evidence must establish that the allegedly inherent feature of the claim was not necessarily present in the prior art method. Considering that Vigsnaes et al. discloses both the administration of HMO to a subject, administration to a subject suffering from atherosclerosis, and a mechanism by which the result is obtained, namely encouraging the growth of the probiotic microorganism A. muciniphila, the relevant question is whether increasing the growth of A. muciniphila would be expected to reduce inflammation caused by macrophages and reduce the size of atherosclerotic plaques, which is reasonably established by Li et al. The two publications of Pessentheiner et al. do not dispute this fact but merely establish that there exists a further direct action of human milk oligosaccharides such as 3’-SL on macrophages and atherosclerotic plaques in the absence of a probiotic microorganism. Discovery of a new mechanism for the functioning of a previously anticipated process does not render the known process novel. It is additionally noted that all of the claims which are rejected over this reference include within their scope oral administration of the human milk oligosaccharides and thus an effect on the intestinal microbiome. Claims such as claim 14 which is directed to parenteral administration, are not included in the rejection.
Therefore the rejection is deemed proper and maintained.
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.
Claims 1, 8, 10-16, 22, 23, and 25-29 are rejected under 35 U.S.C. 103 as being unpatentable over Kang et al. (US pre-grant publication 2019/0030053, of record in previous action) in view of Wang et al. (Reference of record in previous action)
Independent claims 1, 8, and 22 are directed to a method comprising administering two or three oligosaccharides to a subject, wherein these oligosaccharides are described as being selected from a group including a first listing of neutral oligosaccharides including 3’-sialyllactose and a second group which is 6’- sialyllactose. Furthermore claim 1 describes the method as a method of treating or attenuating atherosclerosis while claim 8 describes the method as a method of treating or attenuating complications associated with atherosclerosis. Still further the claims require that the effective amount of the active ingredients significantly reduces inflammation caused by macrophages.
Kang discloses a composition comprising a sialic acid containing oligosaccharide which can be used for treating ore preventing various diseases caused by mitochondrial dysfunction associated with a decrease in PGC-1α (peroxisome proliferator-activated receptor coactivator 1-alpha) expression. (p. 3 paragraphs 23-25) Preferred oligosaccharides include 3’- sialyllactose or 6’- sialyllactose. (p. 4 paragraph 41) In one example administration of 3’-SL or 6’-SL was to treat vascular aging, and atherosclerosis. (p. 20 paragraph 273 – p. 21 paragraph 285) The treatment was described as reducing mitochondrial superoxide production. Kang does not specifically disclose treating or attenuating atherosclerosis. Kang additionally does not specifically disclose administering a combination of both 3’-SL and 6’-SL.
Wang et al. discloses that oxidative DNA damage in atherosclerotic lesions correlates with lesion progression. (p. 423 left column) Furthermore suppression of mitochondrial oxidative stress was seen to protect against atherosclerosis, and decrease inflammation in atherosclerotic lesions. (p. 423 left column last paragraph – p. 425 right column last paragraph) These findings are interpreted as suggesting that treatments to reduce mitochondrial oxidative stress would be useful for treating atherosclerosis. (p. 431 right column third paragraph)
It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to administer a combination of 3’-SL and 6’-SL to a subject in need of treatment for atherosclerosis. One of ordinary skill in the art would have been motivated to do so because Wang indicates that reducing oxidative stress in a subject suffering from atherosclerosis, as would be expected from inducing PGC-1α as described by Kang, would lead to treatment of the condition. Furthermore regarding the combination of two of these active agents, one of ordinary skill in the art would have found it to be obvious to combine two therapeutic agents known to be useful for treating the same patient population. As described in MPEP 2144.06(I), combining equivalents usable for the same purpose, such as the two structurally and functionally similar oligosaccharides described by Kang, is prima facie obvious. Furthermore, the effects of co-administering these oligosaccharides would be expected to be predictable as they work by the same mechanism.
Additionally, while the disclosures of Kang and Wang do not specifically describe their therapeutic method as functioning by suppressing inflammation caused by macrophages, it is reasonably concluded from the art that such an effect is part of the mechanism by which treating atherosclerosis by PGC-1α induction would work. In particular, Kadlec et al. (Reference of record in previous action) describes the role of PGC-1α in vascular biology. (p. 1468 left column second and third paragraph) Kadlec et al. Specifically describes PGC-1α as seen as reducing inflammation and atherosclerotic disease burden. (p. 1470 left column second paragraph) This effect is mediated by macrophages. (p. 1470 left column) Therefore it is reasonably expected that the inflammation being decreased by treatment with 3’-SL and 6’-SL is at least in part caused by macrophages, thereby infringing the present claims.
Regarding claims 16 and 23, Kang describes preparing the composition as a food composition. (p. 8 paragraph 96) Regarding claim 25, Wang describes the therapeutic methods being studied as relevant for human disease. (p. 421 right column last paragraph) Regarding claim 10, this claim recites decreasing incidence or severity of the disease, which would be expected to be an effect of any successful treatment of atherosclerosis. Regarding claim 11, Kang describes pharmaceutical compositions comprising a carrier or excipient. (p. 5 paragraph 61) Regarding claims 12-14, Kang describes oral and parenteral administration, as well as dosage forms such as powders, tablets, and capsules. (p. 5 paragraphs 52-54)
Regarding claim 29, Kang discloses that the dose of the pharmaceutical composition can be a broad range of 0.001-600 mg/kg. (p. 5 paragraph 60) This range indicates that the dose administered is a result-effective variable and thereby suggests determining the appropriate dosage to administer. Since a total dosage of 2g in an adult human would fall within this range, the specific dosage recited in claim 29 is prima facie obvious.
Therefore the invention taken as a whole is prima facie obvious.
Response to Arguments: Applicant’s arguments, submitted July 2, 2026, with respect to the above ground of rejection, have been fully considered and not found to be persuasive to remove the rejection. Applicant argues that Kang does not teach administering a combination of 3’-SIalyllactose and 6’-sialyllactose, and teaches away from using 3’-SL as 6’-SL is disclosed as being superior. However, as discussed in MPEP 2123(II), “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments,” and ”A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." Therefore the fact that 6’SL is disclosed as superior to 3’-SL is not a teaching away from a combination of the two.
Applicant further argues that Kang does not teach or suggest reducing aortic plaques or atherosclerotic lesions as recited in claims 1, 8, and 22, because Kang describes their treatment as increasing expression of PGC-1α, which is known to polarize M2 macrophages, rather than the M1 macrophages which promote plaque development.
Firstly, as described by Wang and acknowledged by Applicant, the cited references disclose a connection between mitochondrial oxidative stress and progression of atherosclerotic lesions. Based on the disclosure of Wang, suppression of mitochondrial oxidative stress itself results in a reduction of atherosclerotic lesions. Therefore it is reasonable to conclude that this effect is present in the treatment methods described by Kang, regardless of the specific effects of PGC-1α on macrophages.
Regarding the disclosure of Kadlec, which is cited as an evidentiary reference, Applicant argues that Kadlec et al. suggests that PGC-1α does not contribute to atherosclerosis. However, the cited passage (p. 1470 right column first paragraph) describes the results of several conflicting studies regarding the effect of PGC-1α. While one study described seems to suggest that deficiency of PGC-1α is not protective against atherosclerosis, other suggested that it is, and the authors concluded that evidence from a later study suggests that the effect of PGC-1α is evident specifically in older subjects. Therefore the preponderance of the evidence suggests that the therapeutic intervention described by Kang does produce the claimed therapeutic outcomes.
For these reasons the rejections are deemed proper and maintained.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Kang et al. in view of Wang et al. as applied to claims 1, 8, 10-16, 22, 23, and 25-29 above, and further in view of Reiche et al. (US pre-grant publication 2015/0164856, of record in previous action)
The disclosure of Vigsnaes is discussed above. Kang et al. in view of Wang et al. does not describe a method wherein the subject is a non-human companion animal. However, Reiche et al. discloses methods of treating metabolic disorders in a feline animal, which is a companion animal or pet according to claim 1. Atherosclerosis is recited as part of a list of metabolic disorders that feline animals can suffer from. (p. 1 paragraph 2, p. 8 paragraph 103) It would have been obvious to one of ordinary skill in the art at the time of the invention to apply the therapeutic method described by Kang et al. to a feline animal suffering from atherosclerosis, in view of the fact that Reiche et al. suggests that feline animals can suffer from this condition and therefore be in need of treatment.
Therefore the invention taken as a whole is prima facie obvious.
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, 8-10, and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 11234992. (of record in previous action, herein referred to as ‘992) Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘992 anticipate the present claims.
Independent claim 1 of ‘992 claims a method of decreasing the size of aortic plaques or atherosclerotic lesions in a subject comprising administering to the subject a composition comprising 3’ – sialyllactose and 6’-sialyllactose, and furthermore indicate that the therapeutic method works by suppressing inflammation caused by macrophages. Dependent claim 3 specifies that the subject suffers from one or more complications which are the same as those recited in present claim 9. Therefore the claims of ‘992 anticipate the present claims.
Claims 11-16, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 11234992. (of record in previous action, herein referred to as ‘992) in view of Kang et al. 2019. (US pre-grant publication 2019/0030053, of record in previous action)
Claims 1 and 3 of ‘992 are as discussed previously. While the claims of ‘992 do not describe the specific dosage forms recited in present claims 11-16, as discussed previously under 35 USC 103, Kang et al. ‘2019 describes these dosage forms as appropriate for administering sialyllactose and similar oligosaccharides for the treatment of atherosclerosis. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to administer the oligosaccharides recited in the claims of ‘992 as one of these pharmaceutical compositions. Furthermore as discussed previously Kang et al. 2019 also describes these compositions as useful for administering to a human, as recited in present claims 6 and 18, and provides a rationale for considering the dosage of oligosaccharide to be a result-effective variable.
Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to administer the therapy claims by ‘992 in the manner defined by the present claims.
Applicant does not separately traverse the above rejections on the ground of nonstatutory double patenting, but rather indicates a willingness to file a terminal disclaimer if the claims are otherwise allowable. As no terminal disclaimer has been filed, the rejections are maintained.
Conclusion
No claims are allowed in this action. 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 ANDREA OLSON whose telephone number is (571)272-9051. The examiner can normally be reached M-F 6am-3:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Y Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANDREA OLSON/Primary Examiner, Art Unit 1693 8/6/2026
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