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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 23, 2026, has been entered.
Information Disclosure Statement
If Applicant wishes for the list of references in the Declaration to be considered, they should be provided to the Office in the form of an IDS and a copy of the references should be provided to the examiner. A size fee assertion may be applicable.
Response to Arguments
The Double Patenting Rejections are held in abeyance, as requested, and are maintained.
Applicant’s arguments and unexpected results have been considered by the examiner in their entirety. A response to both is set forth below.
Applicant notes that it did not file the Declaration previously as an inadvertent omission.
The examiner notes that all arguments and reference therein to Applicant’s Declaration have been considered to date.
Applicant argues that Davis teaches a large genus and only one of which is colchicine-salicylate. Applicant argues that such does not provide a suggestion to elect colchicine-salicylate and there is no motivation to select colchicine salicylate.
The examiner notes that this is exactly why the secondary reference Unsinn is used. Unsinn teaches treating Familial Mediterranean Fever (FMF) with a single form of colchicine salt being colchicine-salicylate. Davis also teaches colchicine forms to treat FMF. Unsinn uses the claimed salt being colchicine-salicylate to treat FMF and in view of Unsinn there is a specific motivation to use the form that was taught to successfully treat FMF, e.g.
Applicant argues that neither Davis nor Unsinn considered that there would be any functional difference in colchicine salts.
The examiner notes that Unsinn established that colchicine-salicylate will treat FMF. This would provide a motivation and reasonable expectation of success in arriving at colchicine-salicylate from the list of salts provided by David.
Applicant argues that colchicine salicylate haves a higher serum level and “potentially” higher efficacy compared to a same dose of colchicine.
The examiner notes that Unsinn uses colchicine salicylate. This is already selected by Unsinn among the many salt forms known in the art, as explained by Davis.
Applicant argues that opinion cannot take the place of an expert declaration. The expert concludes that the use of salicylate salt cannot be regarded as predictable.
The examiner notes that the Office does not disagree with the expert nor does the Office substitute opinion for expert statements of fact. In assessing the probative value of an expert opinion, the examiner must consider the nature of the matter sought to be established, the strength of any opposing evidence, the interest of the expert in the outcome of the case, and the presence or absence of factual support for the expert’s opinion. Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 227 USPQ 657 (Fed. Cir. 1985), cert. denied, 475 U.S. 1017 (1986). In this instance, the unexpected result is the property of colchicine-salicylate. However, Unsinn teaches and uses colchicine-salicylate. One requirement of unexpected results is that is be unexpectedly advantageous as compared to the closest prior art. In this case, the limitation that gives rise to the unexpected result is the API-salicylate salt, which is taught by the prior art. It is not clear how the unexpectedly advantageous form of colchicine-salicylate salt is unexpectedly superior as compared to Unsinn which treats FMF with colchicine-salicylate.
Applicant argues and states the following the Declaration:
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The examiner notes that Unsinn teaches colchicine-salicylate. The chemical, pharmacokinetic or medical properties would appear absent evidence to the contrary part of the salt form as alleged- even when Unsinn used this single salt form.
Moreover, one of ordinary skill would not need to embark on a survey. Unsinn selected and used colchicine-salicylate and it worked. Further, the standard for establishing a prima facie showing of obviousness is not, as intimated by Applicant’s representative, to find a POSA that would not undertake selecting a claimed limitation. The inquiry is more properly whether a person of ordinary skill in the art would select colchicine-salicylate. Unsinn already did so.
With more particular regard to the claimed allegations of unexpected results, the examiner responds:
Declarant indicates that the use of colchicine salicylate improves chemical and pharmacological properties of colchicine. The examiner does not disagree.
Declarant indicates that his/her opinion is based on relevant resources, scientific literature screening, and inquiring as to the known impact of salicylates on colchicine bioavailability.
Declaration indicates that research he/she conducted does not provide a motivation select colchicine-salicylate nor does the literature provide a hint that it would alter PK.
Declarant argues that there was a negative finding in the literature and thus, hindsight would be required to arrive at the colchicine-salicylate salt form.
Declarant screened literature for colchicine salicylate but found no relevant sources regarding the chemical, PK or medical properties of colchicine salicylate.
The examiner responds to the statements by Declaration with only a portion of those statements mentioned above. The examiner notes that the Unsinn reference does not appear to be cited in an IDS in the instants application. The examiner has established a prima facie showing because Davis teaches/renders obvious the claimed API with claimed excipients, e.g. Davis mentions colchicine salicylate as one of many salts. The examiner agrees that this alone with data would not establish a prima facie showing. Unsinn teaches uses a single salt form for treating FMF, which is also taught to be treated by Davis, and that single form is colchicine-salicylate. It is not refuted at this time that colchicine-salicylate has advantageous properties as compared to other salt forms. However, the closest prior art is to show that colchicine-salicylate is unexpectedly advantageous as compared Unsinn.
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
To overcome this rejection, Applicant should explain how the administration and use of colchicine-salicylate as described by Unsinn to reduce the severity and attacks a patient with FMF does not impart the unexpectedly advantageous chemical, PK, and medical properties associated with the salicylate form and attributed to the salicylate form.
The examiner is more than willing to conduct an interview with Applicant at any time if the examiner’s position is not clear. The examiner also notes that he reversed the order of the same references below to highlight the fact that Unsinn did not need to select colchicine-salicylate. From Unsinn’s perspective, colchicine salicylate is the starting point of his/her analysis and he/she is a POSA.
Status of the Claims
Claims 1, 5, 6, 9-14, 16-21, 23, 27, 28, 30, 31, 45, 71, and 72 are pending. Claims 1, 5, 6, 9-14, 16-21 are withdrawn. Claims 23, 27, 28, 30, 31, 45, 71, and 72 are examined.
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 23, 27, 28, 30, 31, 45, 71, and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Unsinn et al., “Familial Mediterranean fever- a case report,” Paiatr Padol 1992;27(4):105-107 Abstract, in view of Davis et al., (US2009/0170952).
Unsinn teaches that colchicine-salicylate is a known salt form of colchicine used as a pharmaceutically active agent, including for chest pain. See Abstract. Unsinn teaches treating Familial Mediterranean Fever (FMF) with a single form of colchicine salt being colchicine-salicylate.
Unsinn does not teach the excipient combination with colchicine-salicylate.
Davis teaches a composition comprising colchicine, waxes, natural and synthetic gums as binders, including hydroxypropylmethyl cellulose (i.e., “hypromellose”) (par. 107), and lactose monohydrate (par. 115). Salts of colchicine are contemplated. See par. 42. The composition can be used to treat Familial Mediterranean Fever as a preferred condition as it is used in an example/embodiment. See par. 160. Further, the colchicine is present in an amount that comprises 0.6 mgA colchicine, wherein mgA means mg of active colchicine (par. 52). Dosage forms can also include 1/2 of the form for administration more times daily, wherein each dosage contains anywhere from 0.3 to 2.4 mgA daily (par. 160). Further, sustained release tablets are created by a coating process if desired (par. 138). One example of a tablet includes colchicine comprising about 0.6 mgA, lactose monohydrate, microcrystalline cellulose, magnesium stearate, and other excipients (par. 16). The blends are compressed to obtain a tablet (par. 23). Advantages to the composition taught by Davis include a low level of impurities, as well as minimizing the need for toxicity testing. Pregelatinized starch and sodium starch glycolate can be used (par. 16). Lubricants including PEG, magnesium stearate, polyethylene oxide, talc and others are taught (par. 111). They can be included in a concentration of 0.01 to 10 wt% (par. 112). Tableting process includes using granules that are wet, dry, milled, mixed with a disintegrant, and more. See par. 23. Davis also teaches salicylic salts forms to be acceptable. See par. 56. Stearic acid is taught as a lubricant. See par. 111.
One embodiment teaches 0.6 mg colchicine (API) 0.6%, pregelatinized starch (disintegrant and filler) 12-16%, microcrystalline cellulose (disintegrant and filler) 20-24%, sodium starch glycolate (disintegrant and filler) 3.9-4.7%, magnesium stearate (lubricant) 0.5-0.7%, and lactose monohydrate (filler). See par. 16. PVP is also an acceptable agent, described by the instant application as a granulating agent.
The examiner acknowledges that some picking and choosing of well-known excipients is required to arrive at the claimed excipient combinations. However, “[w]hen 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.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” Id. Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is…a person of ordinary creativity, not an automaton.” Id. at 1742.
Davis teaches colchicine wherein a single dose provides a Cmax of 1.3 ng/mL and 4 ng/mL (par. 20). Further, peak concentrations generally occur in 0.5 to 2 hours (par. 11). David also teaches an immediate release formulation that releases an amount of at least 75% of the active ingredient within one hour of administration (par. 41). Further, AUC0-T occurs between 4.4 ng-hr/mL and 30.8 ng-hr/mL (par. 20). As such, a person having ordinary skill in the art could easily optimize a concentration of colchicine, which would result in the claimed Cmax, AUC0-T, and blood plasma concentrations that are claimed. According to M.P.E.P. § 2144.05, “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 if the ranges do not overlap- “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.’” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). This is particularly the case because each of the claimed agents are taught and known to be result-effective variables for a particular purpose.
It would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the instant application to arrive at the claimed products in view of Unsinn and Davis. One would be motivated to do so because Davis teaches each of the claimed excipients with the claimed API, and includes teachings that describe the known and result-effective nature and function of each excipient. Further, Davis teaches known salt forms to be unlimited and include the salicylate form while Unsinn teaches colchicine-salicylate as a known salt form of colchicine. Each reference teaches treating Familial Mediterranean Fever. As such, there is a reasonable and predictable expectation of success in arriving at the claimed products in view of the cited prior art and optimizing the concentrations of known result effective variables as well as using functional equivalents to obtain the taught and readily modifiable release profile.
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 23, 27, 28, 30, 31, 45, 71, and 72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,105,319. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘319 patent are directed to a sustained release formulation of colchicine with the claimed excipients. There is a blend of different viscosity HPMC, which would be expected to provide a weighted average of viscosity/properties to the composition. The distinction appears to be optimization of result-effective variables and narrower concentrations with specificity with regard to functionally equivalent components.
Claim 23, 27, 28, 30, 31, 45, 71, and 72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 10,130,585. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘585 patent are directed to a sustained release formulation of colchicine with the claimed excipients. There is a blend of different viscosity HPMC, which would be expected to provide a weighted average of viscosity/properties to the composition. The distinction appears to be optimization of result-effective variables and narrower concentrations with specificity with regard to functionally equivalent components. Further, Davis is directed to treating the claimed subject population including those with cardiovascular disease. This application is not protected from DP rejection under safe harbor provisions because it was filed in a different family.
Claims 23, 27, 28, 30, 31, 45, 71, and 72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 10,610,488. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘488 patent are directed to a sustained release formulation of colchicine with the claimed excipients. There is a blend of different viscosity HPMC, which would be expected to provide a weighted average of viscosity/properties to the composition. The distinction appears to be optimization of result-effective variables and narrower concentrations with specificity with regard to functionally equivalent components.
Claims 23, 27, 28, 30, 31, 45, 71, and 72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No.11,648,206. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘206 patent are directed to a sustained release formulation of colchicine with the claimed excipients. There is a blend of different viscosity HPMC, which would be expected to provide a weighted average of viscosity/properties to the composition. The distinction appears to be optimization of result-effective variables and narrower concentrations with specificity with regard to functionally equivalent components.
As such, no claim is allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D BARSKY whose telephone number is (571)272-2795. The examiner can normally be reached on 9-5 M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy 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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/JARED BARSKY/Primary Examiner, Art Unit 1628