DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 January 2, 2026 has been entered.
Priority
The present application a continuation of 16/307,404 filed on 12/05/2018 which is a 371 of PCT/US2017/036011 filed on June 05, 2017, which claims benefit of PCT/US2017/036011 and PRO 62/345,857 filed on June 05, 2016.
Status of the Claims
Claims 1-2, 5, 11, 13-17, 19, 28-31, 33, 38, 40 are currently pending and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statement(s) (IDS) filed on 1/2/26 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being considered by the Examiner.
Response to Arguments
Applicant’s arguments over the 35 U.S.C. 103 rejection of claims 1-2, 5, 9, 11, 13, 15-17, 28-31, 33, and 44 over Jimenez et al (US 5,486,509, cited in the IDS filed January 31, 2020) in view of Pitre et al (EP 1,952,808 A2, cited in the IDS filed January 31, 2020) is persuasive in part. The rejection is herewith modified to address the amendments. Applicant argues Ohigashi et al. discusses life-threatening hypercalcemia in topical treatment with vitamin D analogues. Applicant argues the Declaration states the amounts of the claimed calcitriol did not result in adverse events nor toxicities. Applicant further argues the prior art references, Jimenez, Pitre, Breastcancer.org fail to teach the particular dosage range having safety and efficacy.
In response, the Examiner points out, the reference relied on as support against use of topical vitamin D, relates to 22-oxacalcitriol (OCT), in treating psoriasis. The Examiner is unclear what the amounts Ohigashi uses and whether those ranges used to treat psoriasis of the skin overlap with the amounts of 6-500 μg used on the scalp taught in Jimenez et al. The Applicant provides no evidence that the amounts taught in Jimenez et al. would result in adverse events or toxicities. It would have been prima facie obvious to one of ordinary skill in the art to utilize the amount of vitamin D taught by Jimenez as a starting point for optimizing the amount of Jimenez utilized to formulate a topical composition comprising Jimenez. Moreover, dosage amount is a result-effective variable, i.e., a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. The Examiner suggests providing a side by side comparison with the closest art of record, showing unexpected or surprising results.
Applicant’s arguments over the 35 U.S.C. 103 rejection of claims 10, 14, 38, 40 over Jimenez et al (US 5,486,509, cited in the IDS filed January 31, 2020) in view of Pitre et al (EP 1,952,808 A2, cited in the IDS filed January 31, 2020) as applied to claims 1-2, 5, 9, 11, 13, 15-17, 28-31, 33, and 44 above, and further in view of Dr. Mercola® Premium Supplements (http://products.mercola.com/vitamin-d-spray/, Internet Archive Wayback Machine date, March 3, 2011) as evidenced by and Sunshine Mist™ Vitamin D Spray product label obtained from the archived webpage: (https://web.archive.org/web/20110303080308/http://mercola.fileburst.com/PDF/product-labels/vitaminD-spray-label-v100.pdf, cited in the IDS filed January 31, 2020) is not persuasive. The rejection is herewith maintained. Applicant’s argument over claims 10, 14, 38, 40 rejections depends on the validity of the previous arguments which were not found persuasive.
Applicant’s arguments over the 35 U.S.C. 103 rejection of claim 19 over Jimenez et al (US 5,486,509, cited in the IDS filed January 31, 2020) in view of Pitre et al (EP 1,952,808 A2, cited in the IDS filed January 31, 2020) as applied to claims 1-2, 5, 9, 11, 13, 15-17, 28-31, 33, and 44 above, and further in view of Breastcancer.org https://www.breastcancer.org/research-news/20100602b, published online June 2, 2010) is not persuasive. The rejection is herewith maintained. Applicant argues Breastcancer.org does not mention a vitamin D compound.
The Examiner points out Jimenez teaches breast cancer cell lines and vitamin D compounds, but does not teach the subject has breast cancer. Jimenez does teach pretreatment with vitamin D3 provided protection from chemotherapy induced alopecia from Adriamycin and cytoxan combination (Table II). Breastcancer.org was incorporated for the teaching that a study suggests that treating early-stage breast cancer with two common chemotherapy medicines followed by a third (doctors call this a sequential approach) has some advantages compared to giving two or three chemotherapy medicines at the same time; the women were treated with two or three common chemotherapy medicines which included adriamycin and Cytoxan.
Applicant’s arguments over the 35 U.S.C. 103 rejection of claims 1-2, 5, 9, 11, 13, 15-17, 28-31, 33, and 44 over Jimenez et al (US 2011/0059917 A1, hereinafter referred to as Jimenez ‘917) in view of Pitre et al (EP 1,952,808 A2, cited in the IDS filed January 31, 2020) is not persuasive. The rejection is herewith maintained. Applicant’s argument over Jimenez et al rejections depends on the validity of the previous arguments which were not found persuasive.
Applicant’s arguments over the 35 U.S.C. 103 rejection of claims 10, 14, 38, 40 over Jimenez et al (US 2011/0059917 A1, hereinafter referred to as Jimenez ‘917) in view of Pitre et al (EP 1,952,808 A2, cited in the IDS filed January 31, 2020) as applied to claims 1-2, 5, 9, 11, 13, 15-17, 28-31, 33, and 44 above, and further in view of Dr. Mercola® Premium Supplements (http://products.mercola.com/vitamin-d-spray/, Internet Archive Wayback Machine date, March 3, 2011) as evidenced by and Sunshine Mist™ Vitamin D Spray product label obtained from the archived webpage: (https://web.archive.org/web/20110303080308/http://mercola.fileburst.com/PDF/product-labels/vitaminD-spray-label-v100.pdf, cited in the IDS filed January 31, 2020) is not persuasive. The rejection is herewith maintained. Applicant’s argument over claims 10, 14, 38, 40 rejections depends on the validity of the previous arguments which were not found persuasive.
Applicant’s arguments over the 35 U.S.C. 103 rejection of claim 19 over Jimenez et al (US 2011/0059917 A1, hereinafter referred to as Jimenez ‘917) in view of Pitre et al (EP 1,952,808 A2, cited in the IDS filed January 31, 2020) as applied to claims 1-2, 5, 9, 11, 13, 15-17, 28-31, 33, and 44 above, and further in view of Breastcancer.org https://www.breastcancer.org/research-news/20100602b, published online June 2, 2010) is not persuasive. The rejection is herewith maintained. Applicant’s argument over claim 19 rejections depends on the validity of the previous arguments which were not found persuasive.
Applicant’s state that the provisional ODP rejection be held in abeyance until patentable subject matter is determined. The rejection is herewith maintained.
The rejections are as below:
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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 1-2, 5, 11, 13-17, 28-31, 33, 38, 40 are rejected under 35 U.S.C. 103 as being unpatentable over Jimenez et al (US 5,486,509, cited in the IDS filed January 31, 2020) in view of Pitre et al (EP 1,952,808 A2, cited in the IDS filed January 31, 2020) and Dr. Mercola® Premium Supplements (http://products.mercola.com/vitamin-d-spray/, Internet Archive Wayback Machine date, March 3, 2011) as evidenced by and Sunshine Mist™ Vitamin D Spray product label obtained from the archived webpage: (https://web.archive.org/web/20110303080308/http://mercola.fileburst.com/PDF/product-labels/vitaminD-spray-label-v100.pdf, cited in the IDS filed January 31, 2020).
Jimenez teaches a method of reducing chemotherapy-induced alopecia comprising administering to a patient undergoing chemotherapy with at least one chemotherapeutic agent 1,25-dihydroxyvitamin D3 in an effective amount; wherein said 1,25-dihydroxyvitamin D3 is administered topically (abstract, claims 1 and 2).The reference teaches 1,25-Dihydroxyvitamin D3, an active metabolite of Vitamin D3, has been shown to increase EGF receptors on breast cancer cells and on a cell line established from rat calvaria (reads on cancers that are solid) (abstract, col 1 lines 55-60). Jimenez teaches a solution of 2-100 μg/ml of 1,25-dihydroxyvitamin D3 in absolute ethanol can be prepared and 3-5 ml of that solution (reads on 6-500 μg) applied directly to the scalp at various points with a dropper followed by scalp massage for 3-5 min to ensure even distribution (col 4 line 19-25). Jimenez further teaches when chemotherapy is involved, this treatment is, advantageously, administered once or twice daily (reads on up to a 24 hour separation) beginning 5-8 days prior to initiation of chemotherapy and continued through the course of chemotherapy, (col 4 line 26) reads on the limitation “wherein step (2) is performed for a sufficient time prior to the commencement of chemotherapy such that the catagen stage of hair follicles is induced in the treated area of the subject”. Administering to a patient undergoing chemotherapy with at least one chemotherapeutic agent, reads on selecting a human subject having cancer who is receiving chemotherapy. Jimenez teaches a topical solution comprising 0.0002-0.1% 1,25-dihyroxyvitamin D3, propylene glycol 10%,30% propylene glycol dicaprylate/dicaprate, 0.05% butylated hydroxytoluene (BHT), 0.05% butylated hydroxyanisole, and ethyl alcohol, absolute q.s. to 100% (see Example VIII, col 9). Thus, the composition taught by Jimenez comprises 10 % propylene glycol and 60% absolute ethanol (see Example VIII, cols 9 and 10). With respect to claims 28, and 32 the wherein limitations of these claims, are considered to simply express the intended result of a process step positively recited, which is not given patentable weight (See MPEP 9111.o4: [T]he court noted (quoting Minton v. Nat'lAss'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQgd 1614, 169o (Fed. Cir. 9oo3)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.'" Hoffer v. Microsoft Corp., 405 F.3d 1396, 1399, 74 USPQgd 1481, 1483 (Fed. Cir. 9oo5)).
Jimenez does not explicitly teach the composition in 105-180 μg or is topically administered using a metered spray unit. Jimenez do not teach the pharmaceutical composition is administered in about 1.0 mL dose and wherein the composition is administered at 0.25 mL to each of the four quadrants of the scalp.
However, Pitre teaches a composition comprising calcitriol that is sprayable (claim 1) wherein the calcitriol is in an amount of between 0.0001 and 20% (claim 2). Pitre teaches the composition is preferably in a dosing spray bottle, for which the application area and dose characteristics are controlled and reproducible; the spray device used consists of a bottle equipped with a 25µl dosing valve [0044]. This reads on a metered spray unit. Pitre further teaches that the composition is suitable for producing a medicinal product intended for treating alopecia, in particular alopecia caused by chemotherapy or radiation [0045].
Moreover, Dr. Mercola Premium Supplements Sunshine Mist™ Vitamin D Spray product label teaches serving size is 6 sprays (approximately 0.78 mL) and that the container contains approximately 32 servings. Thus, Dr. Mercola Premium Supplements teaches a metered pump designed to dispense 0.13-ml, 6 times, and that the container contains about 192 sprays.
It would have been prima facie obvious for a person of ordinary skill in the art at the time of filing of the claimed invention to use the amount of vitamin D as claimed, separate the doses by 10-14 hours and utilize a metered spray unit to deliver composition taught by Jimenez topically to the scalp for treating alopecia induced by chemotherapeutic agents since the prior art teaches this as a method of administration for administering calcitriol for treating alopecia induced by chemotherapeutic agents. The motivation comes from the teaching that vitamin D derivatives are useful in treatment at 2-100 μg/ml and are applied on scalp in 3-5mL, are administered twice a day and have been used in metered spray unit to treat alopecia. Hence a skilled artisan would have had reasonable expectation of successfully achieving similar efficacy and results. Furthermore, 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003). Although, Jimenez does not explicitly teach the composition is anhydrous. However, as set forth above, Pitre teaches a composition comprising calcitriol formulated in a spray composition for use in a metered spray bottle which is useful for treating alopecia of various origins, in particular alopecia caused by chemotherapy, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize a metered spray unit to deliver composition taught by Jimenez topically to the scalp for treating alopecia induced by chemotherapeutic agents since the prior art teaches this as a method of administration for administering calcitriol for treating alopecia induced by chemotherapeutic agents. Pitre further teaches the topical-application composition may be provided in anhydrous form [0041]. It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to formulate the topical spray composition comprising vitamin D in an anhydrous form as taught by Pitre with a reasonable expectation of success since the prior art teaches this is a suitable form for formulating a topical-application composition comprising vitamin D.
It would have been prima facie obvious for a person of ordinary skill in the art at the time filing to utilize the dispense dose, number of spray doses, and amount of dispenses (sprays) the container holds taught by Dr. Mercola Premium Supplements as a starting point for optimizing the spray dispenser to deliver the optimum dose of the vitamin D derivative calcitriol for supplementing the subject without overdosing. Regarding the limitation directed to administering the composition to each of the four quadrants of the scalp, it would have been prima facie obvious to one of ordinary skill in the art to evenly distribute the composition across the scalp in order to evenly treat the scalp to reduce chemotherapy induced alopecia evenly throughout the scalp. The motivation comes from the teaching that a metered pump designed to dispense 0.13-ml, 6 times. Hence, a skilled artisan would have had reasonable expectation of successfully achieving similar efficacy and results.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Jimenez et al (US 5,486,509, cited in the IDS filed January 31, 2020) in view of Pitre et al (EP 1,952,808 A2, cited in the IDS filed January 31, 2020) and Dr. Mercola® Premium Supplements (http://products.mercola.com/vitamin-d-spray/, Internet Archive Wayback Machine date, March 3, 2011) as evidenced by and Sunshine Mist™ Vitamin D Spray product label obtained from the archived webpage: (https://web.archive.org/web/20110303080308/http://mercola.fileburst.com/PDF/product-labels/vitaminD-spray-label-v100.pdf, cited in the IDS filed January 31, 2020) as applied to claims 1-2, 5, 11, 13-17, 28-31, 33, 38, 40 above, and further in view of Breastcancer.org https://www.breastcancer.org/research-news/20100602b, published online June 2, 2010).
Jimenez Pitre and Dr. Mercola® Premium Supplements are discussed above.
Jimenez teaches breast cancer cell lines but does not teach the subject has breast cancer. Jimenez does teach pretreatment with vitamin D3 provided protection from chemotherapy induced alopecia from Adriamycin and cytoxan combination (Table II).
Moreover, Breastcancer.org teaches a study suggests that treating early-stage breast cancer with two common chemotherapy medicines followed by a third (doctors call this a sequential approach) has some advantages compared to giving two or three chemotherapy medicines at the same time; the women were treated with two or three common chemotherapy medicines which included adriamycin and Cytoxan.
It would have been obvious to one of ordinary skill in the art to utilize the method of reducing chemotherapy-induced alopecia suggested by Jimenez and Pitre in a subject having breast cancer treated with Adriamycin and Cytoxan since the prior art teaches pretreatment with vitamin D3 provided protection from chemotherapy induced alopecia from Adriamycin and cytoxan combination and Adriamycin and cytoxan combination is a common chemotherapy for breast cancer, resulting in the practice of the method of claim 19 with a reasonable expectation of success.
Claims 1-2, 5, 11, 13-17, 28-31, 33, 38, 40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jimenez et al (US 2011/0059917 A1, hereinafter referred to as Jimenez ‘917) in view of Pitre et al (EP 1,952,808 A2, cited in the IDS filed January 31, 2020) and Dr. Mercola® Premium Supplements (http://products.mercola.com/vitamin-d-spray/, Internet Archive Wayback Machine date, March 3, 2011) as evidenced by and Sunshine Mist™ Vitamin D Spray product label obtained from the archived webpage: (https://web.archive.org/web/20110303080308/http://mercola.fileburst.com/PDF/product-labels/vitaminD-spray-label-v100.pdf, cited in the IDS filed January 31, 2020).
Jimenez ‘917 teaches a method of preventing or treating alopecia in an individual, comprising topically administering to the individual a pharmaceutical composition comprising a therapeutically effective amount of a vitamin D compound formulated to be delivered to epidermis while substantially avoiding dermis delivery (claim 1) wherein the pharmaceutical composition (abstract, [0024]) comprises about 40% (w/w) propylene glycol and about 60% (w/w) anhydrous absolute ethanol (200 proof, U.S.) (claim 2); wherein the vitamin D compound is 1,25-dihydroxyvitamin D3 (claim 5); wherein the alopecia is chemotherapy-induced alopecia (CIA) (claim 15); wherein alopecia has not commenced in the individual (claim 20), wherein the individual is undergoing or about to undergo chemotherapy (claim 21); wherein the pharmaceutical composition is administered to the individual prior to chemotherapy or concurrent with chemotherapy (claim 22); wherein the pharmaceutical composition does not substantially reduce the efficacy of chemotherapy (claim 24). Jimenez ‘917 teaches the composition can be formulated for topical administration in a spray [0269].
Jimenez ‘917 Jimenez does not explicitly teach the composition in 105-180 μg or is topically administered using a metered spray unit. Jimenez does not teach the pharmaceutical composition is administered in about 1.0 mL dose and wherein the composition is administered at 0.25 mL to each of the four quadrants of the scalp. As set forth above, Jimenez teaches a solution of 2-100 μg/ml of 1,25-dihydroxyvitamin D3. Pitre teaches the spray formula was applied using a spray bottle equipped with a 25 µl dosing valve [0058].
However, Pitre teaches a composition comprising calcitriol that is sprayable (claim 1) wherein the calcitriol is in an amount of between 0.0001 and 20%. Pitre teaches the composition is preferably in a dosing spray bottle, for which the application area and dose characteristics are controlled and reproducible; the spray device used consists of a bottle equipped with a 25µl dosing valve [0044]. This reads on a metered spray unit. Pitre further teaches that the composition is suitable for producing a medicinal product intended for treating alopecia, in particular alopecia caused by chemotherapy or radiation [0045].
Moreover, Dr. Mercola Premium Supplements Sunshine Mist™ Vitamin D Spray product label teaches serving size is 6 sprays (approximately 0.78 mL) and that the container contains approximately 32 servings. Thus, Dr. Mercola Premium Supplements teaches a metered pump designed to dispense 0.13-ml, 6 times, and that the container contains about 192 sprays.
It would have been prima facie obvious for a person of ordinary skill in the art at the time of filing of the claimed invention to use the amount of vitamin D as claimed, separate the doses by 12 hours and utilize a metered spray unit to deliver composition taught by Jimenez topically to the scalp for treating alopecia induced by chemotherapeutic agents since the prior art teaches this as a method of administration for administering calcitriol for treating alopecia induced by chemotherapeutic agents. The motivation comes from the teaching that vitamin D derivatives are useful in treatment at 2-100 μg/ml and are applied on scalp in 3-5mL, are administered twice a day and have been used in metered spray unit to treat alopecia. Hence a skilled artisan would have had reasonable expectation of successfully achieving similar efficacy and results. Furthermore, 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003). Although, Jimenez does not explicitly teach the composition is anhydrous. However, as set forth above, Pitre teaches a composition comprising calcitriol formulated in a spray composition for use in a metered spray bottle which is useful for treating alopecia of various origins, in particular alopecia caused by chemotherapy, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize a metered spray unit to deliver composition taught by Jimenez topically to the scalp for treating alopecia induced by chemotherapeutic agents since the prior art teaches this as a method of administration for administering calcitriol for treating alopecia induced by chemotherapeutic agents. Pitre further teaches the topical-application composition may be provided in anhydrous form [0041]. It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to formulate the topical spray composition comprising vitamin D in an anhydrous form as taught by Pitre with a reasonable expectation of success since the prior art teaches this is a suitable form for formulating a topical-application composition comprising vitamin D.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the dispense dose, number of spray doses, and amount of dispenses (sprays) the container holds taught by Dr. Mercola Premium Supplements as a starting point for optimizing the spray dispenser to deliver the optimum dose of the vitamin D derivative calcitriol for supplementing the subject without overdosing. Regarding the limitation directed to administering the composition to each of the four quadrants of the scalp, it would have been prima facie obvious to one of ordinary skill in the art to evenly distribute the composition across the scalp in order to evenly treat the scalp to reduce chemotherapy induced alopecia evenly throughout the scalp. The motivation comes from the teaching that a metered pump designed to dispense 0.13-ml, 6 times. Hence, a skilled artisan would have had reasonable expectation of successfully achieving similar efficacy and results.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Jimenez et al (US 2011/0059917 A1, hereinafter referred to as Jimenez ‘917) in view of Pitre et al (EP 1,952,808 A2, cited in the IDS filed January 31, 2020) and Dr. Mercola® Premium Supplements (http://products.mercola.com/vitamin-d-spray/, Internet Archive Wayback Machine date, March 3, 2011) as evidenced by and Sunshine Mist™ Vitamin D Spray product label obtained from the archived webpage: (https://web.archive.org/web/20110303080308/http://mercola.fileburst.com/PDF/product-labels/vitaminD-spray-label-v100.pdf, cited in the IDS filed January 31, 2020) as applied to claims 1-2, 5, 11, 13-17, 28-31, 33, 38, 40 above, and further in view of Breastcancer.org https://www.breastcancer.org/research-news/20100602b, published online June 2, 2010).
Jimenez Pitre and Dr. Mercola® Premium Supplements are discussed above.
Jimenez teaches breast cancer cell lines but does not teach the subject has breast cancer. Jimenez does teach pretreatment with vitamin D3 provided protection from chemotherapy induced alopecia from Adriamycin and cytoxan combination (Table II).
Moreover, Breastcancer.org teaches a study suggests that treating early-stage breast cancer with two common chemotherapy medicines followed by a third (doctors call this a sequential approach) has some advantages compared to giving two or three chemotherapy medicines at the same time; the women were treated with two or three common chemotherapy medicines which included adriamycin and Cytoxan.
It would have been obvious to one of ordinary skill in the art to utilize the method of reducing chemotherapy-induced alopecia suggested by Jimenez and Pitre in a subject having breast cancer treated with Adriamycin and Cytoxan since the prior art teaches pretreatment with vitamin D3 provided protection from chemotherapy induced alopecia from Adriamycin and cytoxan combination and Adriamycin and cytoxan combination is a common chemotherapy for breast cancer, resulting in the practice of the method of claim 19 with a reasonable expectation of success.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2, 5, 11, 13-17, 19, 28-31, 33, 38, 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 5,486,509 in view of Pitre et al (EP 1,952,808 A2, cited in the IDS filed January 31, 2020).
The instant claims are directed to a method of preventing or mitigating chemotherapy-induced alopecia in a human subject comprising the steps of:(1) selecting a human subject having a cancer and who is scheduled to receive, or is receiving, a chemotherapy; and (2) topically administering a pharmaceutical composition comprising a vitamin D compound in a total daily dose of 105 µg to 180 µg of the vitamin D compound to the scalp of the subject, wherein step (2) is performed prior to and/or concurrently with the chemotherapy, thereby preventing or mitigating chemotherapy-induced alopecia in the subject (claim 1), wherein the pharmaceutical composition is administered using a metered spray unit (claim 13).
The previously allowed claims are directed to a method of reducing chemotherapy-induced alopecia comprising administering an effective amount of vitamin D3 or derivative thereof (claim 1) wherein said derivative is 1,25-dihydroxyvitamin D3 (claim 2) wherein said vitamin D3 is administered topically (claim 3), wherein the composition is administered prior to the initiation of said chemotherapy (claim 9). The previously allowed claims do not specifically recite topically is administered using a metered spray unit.
However, Pitre teaches a composition comprising calcitriol that is sprayable (claim 1) wherein the calcitriol is in an amount of between 0.0001 and 20% (claim 2). Pitre teaches the composition is preferably in a dosing spray bottle, for which the application area and dose characteristics are controlled and reproducible; the spray device used consists of a bottle equipped with a 25µl dosing valve [0044]. This reads on a metered spray unit. Pitre further teaches that the composition is suitable for producing a medicinal product intended for treating alopecia, in particular alopecia caused by chemotherapy or radiation [0045]. The Examiner notes that 1,25-dihydroxyvitamin D3 is equivalent to calcitriol.
As such, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize a metered spray unit to deliver the composition recited by the previously allowed claims topically to the scalp for treating alopecia induced by chemotherapeutic agents since the prior art teaches this as a method of administration for administering calcitriol for treating alopecia induced by chemotherapeutic agents.
Claims 1-2, 5, 11, 13-17, 19, 28-31, 33, 38, 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of U.S. Patent No. 6,291,443 B1 in view of Pitre et al (EP 1,952,808 A2, cited in the IDS filed January 31, 2020).
The instant claims are directed to a method of preventing or mitigating chemotherapy-induced alopecia in a human subject comprising administering a pharmaceutical composition comprising a therapeutically effective amount of a vitamin D compound to the scalp of the subject using a metered spray unit.
The previously allowed claims are directed to a method of reducing chemotherapy-induced alopecia comprising administering an effective amount of vitamin D3 or derivative thereof (claim 1) wherein said derivative is 1,25-dihydroxyvitamin D3 (claim 2) wherein said vitamin D3 is administered topically (claim 3), wherein the composition is administered prior to the initiation of said chemotherapy (claim 9). The previously allowed claims do not specifically recite topically is administered using a metered spray unit.
However, Pitre teaches a composition comprising calcitriol that is sprayable (claim 1) wherein the calcitriol is in an amount of between 0.0001 and 20% (claim 2). Pitre teaches the composition is preferably in a dosing spray bottle, for which the application area and dose characteristics are controlled and reproducible; the spray device used consists of a bottle equipped with a 25µl dosing valve [0044]. This reads on a metered spray unit. Pitre further teaches that the composition is suitable for producing a medicinal product intended for treating alopecia, in particular alopecia caused by chemotherapy or radiation [0045]. The Examiner notes that 1,25-dihydroxyvitamin D3 is equivalent to calcitriol.
As such, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize a metered spray unit to deliver the composition recited by the previously allowed claims topically to the scalp for treating alopecia induced by chemotherapeutic agents since the prior art teaches this as a method of administration for administering calcitriol for treating alopecia induced by chemotherapeutic agents.
Claims 1-2, 5, 11, 13-17, 19, 28-31, 33, 38, 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-57 of U.S. Patent No. 9,901,637 B2 in view of Pitre et al (EP 1,952,808 A2, cited in the IDS filed January 31, 2020).
The instant claims are directed to a method of preventing or mitigating chemotherapy-induced alopecia in a human subject comprising the steps of:(1) selecting a human subject having a cancer and who is scheduled to receive, or is receiving, a chemotherapy; and (2) topically administering a pharmaceutical composition comprising a vitamin D compound in a total daily dose of 105 µg to 180 µg of the vitamin D compound to the scalp of the subject, wherein step (2) is performed prior to and/or concurrently with the chemotherapy, thereby preventing or mitigating chemotherapy-induced alopecia in the subject (claim 1), wherein the pharmaceutical composition is administered using a metered spray unit (claim 13).
The previously allowed claims are directed to a method of treating chemotherapy-induced alopecia comprising topically administering to the individual a pharmaceutical composition comprising a therapeutically effective amount of a vitamin D compound and a carrier, wherein the carrier consists of propylene glycol and anhydrous absolute ethanol at a % (w/w) ratio of propylene glycol to ethanol range which includes 40:60 (claim 1) (which is the same or similar to the carrier and ratio of instant claims 23 and 24); wherein the vitamin D compound is 1,25-dihydroxyvitamin D3 (claim 2); wherein alopecia has not commenced in the individual (claim 5), wherein the composition is administered to the individual prior to administration of chemotherapy or concurrent with administration of chemotherapy to the individual (claim 11); wherein the pharmaceutical composition does not substantially reduce the efficacy of the chemotherapy (claim 7). The previously allowed claims do not specifically recite that the topically administered composition is administered using a metered spray unit.
However, Pitre teaches a composition comprising calcitriol that is sprayable (claim 1) wherein the calcitriol is in an amount of between 0.0001 and 20% (claim 2). Pitre teaches the composition is preferably in a dosing spray bottle, for which the application area and dose characteristics are controlled and reproducible; the spray device used consists of a bottle equipped with a 25µl dosing valve [0044]. This reads on a metered spray unit. Pitre further teaches that the composition is suitable for producing a medicinal product intended for treating alopecia, in particular alopecia caused by chemotherapy or radiation [0045]. The Examiner notes that 1,25-dihydroxyvitamin D3 is equivalent to calcitriol.
As such, since the instant claims are directed to a method of preventing chemotherapy-induced alopecia comprising administering a therapeutically effective amount of a vitamin D compound to a patient undergoing or about to undergo chemotherapy, and since Pitre teaches a composition comprising calcitriol formulated in a spray composition for use in a metered spray bottle which is useful for treating alopecia of various origins, in particular alopecia caused by chemotherapy, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize a metered spray unit to deliver composition taught by Jimenez topically to the scalp for treating alopecia induced by chemotherapeutic agents since the prior art teaches this as a method of administration for administering calcitriol for treating alopecia induced by chemotherapeutic agents.
Regarding the amounts of vitamin D of instant claims 6-8 and 10, the previously allowed claims are directed to wherein the pharmaceutical composition comprises 3-100 μg/mL of 1,25-dihydroxyvitamin D3; and wherein the pharmaceutical composition comprises about 5, 10 or 20 μg/mL of 1,25-dihydroxyvitamin D3. It would have prima facie obvious to utilize the amounts of the previously granted claims to arrive at the doses and amounts of the sprayable composition of the instant claims. Similarly, it would have been well with the skill of the skilled artisan to optimize the treatment regimen recited in the previously granted claims to arrive at the treatment regimen of instant claims 3, 4, 9, 11 and 12, Jimenez ‘917 teaches the vitamin D compounds of the invention is topically administered to the scalp twice daily each day for two consecutive weeks prior to the commencement of chemotherapy in order to prevention or reduce the severity of any CIA that may occur upon commencement of chemotherapy [0172]. Two weeks prior to commencement of chemotherapy reads on the limitation “wherein step (2) is performed for a sufficient time prior to the commencement of chemotherapy such that the catagen stage of hair follicles is induced in the treated area of the subject” as evidenced by instant claim 4.
Regarding previously allowed claims 49-58 which are directed to a pharmaceutical composition comprising vitamin D compounds, the composition of the previously allowed claims would anticipate the instantly claimed composition.
In Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co., 95 USPQ2d 1797 (Fed. Cir. 2010), the Court determined that Claims of a later patent were held invalid for obviousness-type double patenting when the earlier patent claimed a compound and disclosed its utility in specification, and later patent claimed a method of using compound for use described in specification of earlier patent.
Claims 1-2, 5, 11, 13-17, 19, 28-31, 33, 38, 40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 41, 43-49, 51, 52, 54-56, and 58-63 of copending Application No. 15/872,669 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because: The copending claims are directed to a pharmaceutical composition comprising a vitamin D compound, propylene glycol and ethanol which would anticipate the instantly claimed composition. The specification of the copending claims discloses the composition can be formulated in a spray formulation, and the compositions are useful for preventing or treating alopecia in an individual by topically administering the composition (page 2, lines 3-4) wherein the alopecia is chemotherapy induced alopecia (page 4, lines 21-22).
In Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co., 95 USPQ2d 1797 (Fed. Cir. 2010), the Court determined that Claims of a later patent were held invalid for obviousness-type double patenting when the earlier patent claimed a compound and disclosed its utility in specification, and later patent claimed a method of using compound for use described in specification of earlier patent.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reference of relevance:
Gamady A, Koren R, Ron D, Liberman UA, Ravid A. Vitamin D enhances mitogenesis mediated by keratinocyte growth factor receptor in keratinocytes. J Cell Biochem. 2003 Jun 1;89(3):440-9. doi: 10.1002/jcb.10508. PMID: 12761878.
Schilli MB, Paus R, Menrad A. Reduction of intrafollicular apoptosis in chemotherapy-induced alopecia by topical calcitriol-analogs. J Invest Dermatol. 1998 Oct;111(4):598-604. doi: 10.1046/j.1523-1747.1998.00350.x. PMID: 9764839.
Amy Han, Georgann Anetakis Poulos & Paradi Mirmirani (2006) Expanding research and development of novel agents for the treatment and prevention of chemotherapy-induced alopecia, Expert Opinion on Therapeutic Patents, 16:6, 773-781
Holick MF. Noncalcemic actions of 1,25-dihydroxyvitamin D3 and clinical applications. Bone. 1995 Aug;17(2 Suppl):107S-111S. doi: 10.1016/8756-3282(95)00195-j. PMID
Conclusion
No claims allowed.
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/LAYLA SOROUSH/ Primary Examiner, Art Unit 1622