DETAILED ACTION
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 .
Application Status
2. Claims 1 and 9 are amended. Claims 19 and 20 are newly added.
3. Claims 11-18 (drawn to Group II) remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
4. Applicant previously elected the following species: (a) naltrexone, (b) calcitriol, and (d) simultaneous administration. The non-elected species remain withdrawn from further consideration as drawn to nonelected subject matter.
5. Claims 1-4, 9, 19 and 20 are under examination with the elected species and are the subject of this office action.
Information Disclosure Statement
6. The information disclosure statement (IDS) submitted on January 20, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner, please refer to the signed copy of Applicant’s PTO-1449 form, attached herewith.
Priority
7. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 365(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
8. The disclosure of the prior-filed foreign application, Application No. GB 1805207.6, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application, as follows:
Applicant’s claims, as amended, require the limitation of the daily dose of Vitamin D product, i.e., “wherein the vitamin D product is administered at a daily dose in the range of about 2,000 IU to 8,000 IU per dosage form.” However, in foreign priority document GB 1805207.6, the only mention of dose amount of the vitamin D product is:
“[i]n another embodiment, the vitamin D or analogue thereof of pharmaceutically acceptable salt of either is administered at a dose in the range of about 400 IU to about 10,000 IU per dosage form,” (page 7, lines 23-25 and see page 9, lines 1-2).
Thus foreign application GB 1805207.6 fails to provide support for the daily dose amount or daily dose range of the Vitamin D product, and the instant claims are afforded benefit of priority to U.S. Application 17/042,904, filed September 28, 2020.
New Claim Rejections - 35 USC § 112
9. 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.
10. Claims 1-4, 9, 19 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.
This rejection is necessitated as a result of Applicant’s amendment to the claims.
11. Claim 1, as amended, recites the limitation of the dose amount of Vitamin D product: “wherein the vitamin D product is administered at a daily dose in the range of about 2,000 IU to 8,000 IU per dosage form,” [emphasis added] which is confusing, because it is not clear from the claim if the recited amount of “about 2,000 IU to 8,000 IU” is the total daily dose amount, or if said recited amount is the amount contained in each dosage form. Clarification is requested.
The Specification, paragraph [0031], fails to clarify whether the total daily dose amount or the amount per dosage form is intended:
“the vitamin D or analogue thereof, or pharmaceutically acceptable salt of either is administered at a daily dose in the range of about 400 IU to about 10,000 IU per dosage form, preferably in the range of about 2,000 to about 8,000, more preferably in the range of about 3,000 to 7,000,” however, in Examples 1-3, each patient is started on a total dose of Vitamin D3 of 5,000 units per day (pages 11-13).
In view of a broadest reasonable interpretation for the purpose of applying prior art, the limitation of “wherein the vitamin D product is administered at a daily dose in the range of about 2,000 IU to 8,000 IU per dosage form” is construed to mean:
“wherein the vitamin D product is administered at a dose in the range of about 2,000 IU to 8,000 IU per day.”
12. Claim 19 recites the limitation of the dose amount of Vitamin D product: “wherein the vitamin D product is administered at a daily dose in the range of about 3,000 IU to 7,000 IU per dosage form,” [emphasis added] which is confusing, because it is not clear from the claim if the recited amount of “about 3,000 IU to 7,000 IU” is the total daily dose amount, or if said recited amount is the amount contained in each dosage form. Clarification is requested.
In view of a broadest reasonable interpretation for the purpose of applying prior art, the limitation of “wherein the vitamin D product is administered at a daily dose in the range of about 3,000 IU to 7,000 IU per dosage form” is construed to mean:
“wherein the vitamin D product is administered at a dose in the range of about 3,000 IU to 7,000 IU per day.”
13. Claim 20 recites the limitation of the dose amount of Vitamin D product: “wherein the vitamin D product is administered at a daily dose of about 5,000 IU per dosage form,” [emphasis added] which is confusing, because it is not clear from the claim if the recited amount of “about 5,000 IU” is the total daily dose amount, or if said recited amount is the amount contained in each dosage form. Clarification is requested.
In view of a broadest reasonable interpretation for the purpose of applying prior art, the limitation of “wherein the vitamin D product is administered at a daily dose of about 5,000 IU per dosage form” is construed to mean:
“wherein the vitamin D product is administered at a dose in the range of about 5,000 IU per day.”
14. Claims 2-4 and 9 are rejected as being dependent upon and including all of the limitations of claim 1.
Previous Claim Rejections - 35 USC § 103
15. Claims 1-4 and 9 were previously rejected under 35 U.S.C. 103 as being unpatentable over Sherman and Atkinson, U.S. Pat. No. 4,857,533 A, in view of Lurong and Nguyen, Clinical Rheumatology 2012.
16. In view of Applicant’s amendments to the claims, the previous rejection is withdrawn and the following rejection is newly applied.
New Claim Rejections - 35 USC § 103
17. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
18. Claims 1-4, 9, 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Sherman and Atkinson, U.S. Pat. No. 4,857,533 A, and further in view of Lima et al., (Arthritis Care and Research 2016), as evidenced by Patel et al., (Practical Gastroenterology 2021).
This rejection is newly applied as necessitated by Applicant’s amendment to the claims.
Claim 1, as amended, is drawn to a method of treating an autoimmune disease (more specifically, Systemic Lupus Erythematosus (SLE)), comprising administering separately, sequentially or simultaneously (more specifically, simultaneously (claim 3)) to a subject in need thereof,
(i) a naltrexone product or an analogue thereof, (more specifically, naltrexone (claim 9)), at a dose of from 1 to 5 mg, and
(ii) the vitamin D product calcitriol, administered at a daily dose in the range of about 2,000 IU to 8,000 IU per dosage form.
In view of a broadest reasonable interpretation for the purpose of applying prior art, the limitation of :
“wherein the vitamin D product is administered at a daily dose in the range of about 2,000 IU to 8,000 IU per dosage form” is construed to mean:
“wherein the vitamin D product is administered at a dose in the range of about 2,000 IU to 8,000 IU per day.”
Claim 19 is drawn to claim 1 and limits wherein the vitamin D product is administered at a daily dose in the range of about 3,000 IU to 7,000 IU per dosage form.
In view of a broadest reasonable interpretation, the limitation of “wherein the vitamin D product is administered at a daily dose in the range of about 3,000 IU to 7,000 IU per dosage form” is construed to mean:
“wherein the vitamin D product is administered at a dose in the range of about 3,000 IU to 7,000 IU per day.”
Claim 4 is drawn to claim 1, and limits wherein the naltrexone product and the vitamin D product are administered as a combined preparation.
19. Sherman teaches a method of treating systemic lupus erythematosus in a patient in need thereof, comprising administering nalmefene orally in 1.0 mg tablets twice daily, (see Example, column 5). Sherman additionally recites a method of treating systemic lupus erythematosus in a patient in need thereof comprising administering nalmefene or naltrexone in an oral dosage form comprising a tablet, capsule, caplet or liquid containing from about 0.5 to about 50.0 mg nalmefene or naltrexone, which meets the limitation of from 1 to 5 mg required by instant Claim 1 (see Sherman claims 1-5). Considering that the genus of narcotic antagonists disclosed by Sherman comprises only two compounds, i.e., nalmefene and naltrexone, one skilled in the art before the effective filing date of the claimed invention would have immediately envisaged selecting naltrexone for the treatment of systemic lupus erythematosus in a patient in need thereof, and would have a reasonable expectation of success.
20. Sherman is silent to the administration of calcitriol.
21. Yet, Lima et al. teaches that vitamin D supplementation in patients with systemic lupus erythematosus (SLE) resulted in decreased disease activity and improved fatigue in SLE patients (See abstract). Lima et al. teach the administration of vitamin D in the form of oral cholecalciferol tablets at a dose of 50,000 IU/week (page 92, right column, under “Randomization and blinding”), equivalent to a dose of 7,142.86 IU/day, which meets the limitation of about 2,000 IU to 8,000 IU per day required by claim 1 and about 3,000 IU to about 7,000 IU per day required by claim 19. And, as evidenced by Patel et al., both cholecalciferol and calcitriol are formulations in the Vitamin D family: cholecalciferol is Vitamin D3, while calcitriol is the active form of cholecalciferol (page 22, Table 1). Considering that the genus of Vitamin D analogs in Table 1 comprises only four compounds, i.e., ergocalciferol, cholecalciferol, calcidiol, and calcitriol, one skilled in the art would have immediately envisaged substituting the active metabolite calcitriol for cholecalciferol in the treatment of systemic lupus erythematosus in a patient in need thereof.
22. As such, one skilled in the art before the effective filing date of the claimed invention would have been motivated to administer calcitriol at a dose of about 7,000 IU/day to a patient suffering from SLE, with a reasonable expectation of success.
23. Thus, nothing unobvious is seen in combining the teachings of Sherman and Lima et al. in a method of simultaneously administering a combination of naltrexone and calcitriol to treat SLE in a patient in need thereof. The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law, please see In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings). Furthermore, MPEP 2144 teaches that the strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination.
24. In the instant case, two known compounds which individually demonstrate activity against SLE when administered orally in the form of tablets could be combined for simultaneous administration (or in a combined preparation as recited in claim 4) in order to achieve an additive effect, with the expected result of an effective treatment for the autoimmune disease SLE.
25. Please refer to MPEP 2144.06 “I. COMBINING EQUIVALENTS KNOWN FOR THE SAME PURPOSE” wherein Kerkhoven is specifically referenced:
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious).
26. As stated by the Court in KSR International Co., v. Teleflex Inc., 127 US 1727 (2007), “when a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious” (quoting Sakraida v. AG Pro, Inc., 425 US 273 (1976); see also: Merck v. Biocraft (874 F.2d 804, 807 (Fed. Cir. 1989), indicating that it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands; Sundance, Inc. v. DeMonte Fabricated, Ltd., 550 F.3d 1356 (Fed. Cir. 2008): a claimed invention is obvious is it is a combination of known prior art elements that would reasonably have been expected to maintain their respective properties or functions after they had been combined.
As such, claims 1, 3, 4, and 19 are prima facie obvious.
Claim 2 is drawn to claim 1, and limits wherein the vitamin D product is administered to the subject in an amount sufficient to bring the subject's blood vitamin D concentration to within a range of from 40 to 120 ng/ml.
27. Claim 2 depends from claim 1 and is drafted in terms of the intended outcome of the administration of the Vitamin D: “...wherein the vitamin D product is to be administered to the subject in an amount sufficient to bring the subject's blood vitamin D concentration to within a range of from 40 to 120 ng/ml.” However, a claimed composition maybe obvious because it was suggested by, or structurally similar to, a prior art composition even though a particular benefit of the claimed composition 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 nonobviousness. If the prior art composition does in fact possess a particular benefit, even though the benefit is not recognized in the prior art, Applicant's recognition of the benefit is not in itself sufficient to distinguish the claimed composition from the prior art, In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1991). In this case, the increase in blood vitamin D concentration is considered a latent property of the administration of calcitriol, as previously disclosed by Lima et al., and the alleged unexpected result does not confer patentability.
As such, claim 2 is prima facie obvious.
Claim 20 is drawn to claim 1 and limits wherein the vitamin D product is administered at a daily dose of about 5,000 IU per dosage form.
In view of a broadest reasonable interpretation, the limitation of “wherein the vitamin D product is administered at a daily dose of about 5,000 IU per dosage form” is construed to mean:
“wherein the vitamin D product is administered at a dose in the range of about 5,000 IU per day.”
28. Lima et al. suggest the treatment of SLE comprising administering vitamin D in the form of calcitriol tablets at a dose of 50,000 IU/week equivalent to a dose of 7,142.86 IU/day ((page 92, right column, under “Randomization and blinding”). It would have been obvious to one of skill in the art before the effective filing date of the claimed invention to use the starting dose of about 7000 IU/day and optimize said dose in order to achieve a beneficial effect in a method of treating SLE.
Moreover, the determination of known effective amounts of known active agents to be administered to treat the same disease is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art. And, discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art. See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980), thus resulting in the practice of claim 20, with a reasonable expectation of success.
As such, claim 20 is prima facie obvious.
Response to Arguments
29. Applicant argues that that the treatment of both SLE and thyroiditis is demonstrated in the Examples in the Specification, and that based upon said Examples, there has been a showing that the therapeutic pathways of naltrexone and vitamin D interact in such a way that significantly enhances the therapeutic effect when used in combination. Applicant alleges that based on the data, Vitamin D products such as calcitriol support the function of dendritic cells and so combining it with naltrexone, which has surprisingly been found to have its own dendritic cell supporting effects, creates a synergistic effect that enhances immune function further, amounting to a significantly greater than what would be expected through simple additive effects observed when both agents are administered in isolation (e.g., when vitamin D products are administered without naltrexone).
30. Applicant's arguments have been fully considered but they are not persuasive. Regarding Applicant’s assertion of synergism, even if it was agreed upon that the claimed method provided synergistic results, more would be required to show nonobviousness, as synergism is not per se unexpected. See In re Diamond, 360 F. 2d 214, 218 ( CCPA 1966). (“What section 103 requires is ‘unexpected synergism’ ... “ (pg. 216, n.7); “we attribute no magic status to synergism per se since it may be expected or unexpected"” (pg. 218)(emphasis added)). In the instant case, the combination of familiar elements, (i.e., naltrexone and calcitriol, each previously taught for the treatment or supplemental treatment of SLE in the same dose amounts), according to known methods is likely to be obvious when it does no more than yield predictable results, i.e., successful treatment of SLE in a patient in need thereof.
31. Sherman in view of Lima et al. as evidenced by Patel suggest the combined administration of naltrexone and calcitriol in the form of oral tablets at dosage amounts that are within the dose ranges recited by the instant claims, for the treatment of SLE in a patient in need thereof. As such, one skilled in the art before the effective filing date of the claimed invention would have been motivated to combine the teachings of the prior art for an improved treatment of SLE in a patient in need thereof, with a reasonable expectation of success.
Conclusion
32. In conclusion, claims 1-4, 9 and 11-20 are present in the application. Claims 11-18 are withdrawn from consideration. Claims 1-4, 9, 19 and 20 are rejected. No claim is currently allowable.
33. 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.
34. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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