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 .
Amendments
Claims 1-4 have been amended to require co-administration monthly for at least six months.
Claim 13 has been canceled.
Claim 72 has been amended to replace “concomitant administration” with sequential co-administration.
Election/Restrictions
The present application remains examined per applicant’s election of the species “chronic refractory gout” as the specific type of “gout” in the reply filed on 02/21/2023.
Claim 31 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1-5, 7, 20, 24, 28, 35, 39, 53, 58, 68-69, and 72 are directed to the elected invention and have been examined per the species election.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/07/2026 is in compliance with the provisions of 37 C.F.R. 1.97. All references cited in this IDS have been fully considered.
Claim Rejections - 35 USC § 112
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.
Previous rejection under 35 U.S.C. § 112(b)
RE: Rejection of claim 72 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 72 was rejected as being indefinite. Applicant disagrees with the rejection of record but, in the interest of advancing prosecution, has amended the claim to recite “sequential co-administration”.
Because it is now clear that the administration occurs in sequence (i.e., not in the same administration), the claim is no longer considered to be indefinite and the rejection is withdrawn.
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 (i.e., changing from AIA to pre-AIA ) 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.
The factual inquiries 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.
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.
Previous rejections under 35 U.S.C. § 103
Response to applicant’s arguments
Applicant disagrees with the rejection of record but has instead amended claims 1-4 to now require sequential co-administration monthly for at least six months. Applicant maintains that examiner has not met any of the requirements of establishing obviousness (Remarks, p. 10, par. 2). Specifically, applicant asserts that the teachings of Selecta and Guttman do not provide the methods of the claims nor establish that their result would be predictable (Id.).
First, applicant argues that Selecta fails to teach the claimed subject population (subjects having symptomatic chronic gout inadequately controlled with a xanthine oxidase inhibitor (XOI) and a serum uric acid level of > 7 mg/dL and (a) three or more gout flares within the past 18 months; and/or (b) a history of inter-flare intervals of one week or less). Instead, applicant argues that Selecta’s population are patients having “symptomatic gout and elevated uric acid levels ≥ 6 mg/dL, with established or symptomatic gout” (Remarks, p. 10, par. 3). Applicant states that the range of ≥ 6 mg/dL does not necessarily mean that a serum uric acid at higher than > 7 mg/Dl.
Second, applicant argues that Selecta fails to teach “sequential co-administration that is monthly for at least six months” and it has not been established that such sequential co-administration would be predictably efficacious in any subject let alone the subject of the claims. Applicant continues by arguing that it is the inventors’ surprising discovery that subjects can be effectively treated with these methods and without the guidance of this instant application, one of ordinary skill in the art would have had no reason to single out the subjects of the claims for treatment with the recited compositions and for the claimed time period. Applicant supports this assertion by arguing that this unexpected benefit has been demonstrated in several articles and posters (summarized in p. 11, par. 3 through p. 13, par. 1).
Third, applicant argues that the examiner has used impermissible hindsight to arrive at the instant rejections.
Applicant’s arguments have been fully considered but are not sufficient to overcome a rejection over the claims, as amended, for the reasons discussed below.
With respect to the first argument, the examiner strongly disagrees with applicant’s assertion that a teaching of treating a patient population having a sUA of ≥ 6 mg/dL is not probative of success for treating a patient population having a sUA of > 7 mg/dL. By nature, the range taught by Selecta encompasses the exact range recited in the instant claims. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP § 2144.05(I)). Applicant’s range clearly overlaps with the prior art range because it encompasses every value of sUA except 6.00-6.99 mg/dL. As discussed in the previous response to applicant’s arguments, a therapy which has been suggested to be effective in treating a patient having an sUA of ≥ 6 mg/dL would have also been reasonably expected to successfully treat a patient having an sUA of > 7 because both patient populations have elevated sUA and because the instantly claimed patient population falls entirely within the patient population described by Selecta. In fact, in order to adopt applicant’s theory of unpredictability, a person having ordinary skill in the art would have to set aside the explicit teachings of Selecta (≥ 6 mg/dL ) and instead determine that Selecta merely included patients having sUA levels of 6.00-6.99 and not ≥ 6 mg/dL. Additionally, it is noted that applicant’s own disclosure states that “elevated serum uric acid level” refers to any level of uric acid in a subject’s serum and “the subject of any one of the methods provided herein can have a serum uric acid level of ≥ 5 mg/dL” (Specification, p. 20, lines 19-25). Thus, applicant is prophetically asserting that their composition would be effective at serum uric acid levels lower than what is described in Selecta while also arguing that the patient’s serum uric acid level causes a degree of unpredictability.
With respect to the second argument, the examiner acknowledges that neither Selecta nor Guttman teach sequential co-administration “monthly for at least six months”. Nonetheless, a person having ordinary skill in the art could have arrived at this range through routine optimization of Selecta’s methods. For the reasons discussed in the rejection of record, Selecta in view of Guttman renders obvious sequential co-administration of 1) a composition comprising synthetic nanocarriers comprising an immunosuppressant and 2) a composition comprising pegadricase. The claims differ from the prior art only in that applicant has now narrowed the method to involve monthly co-administration for at least six months. It was known that SEL-212 could be administered monthly in repeated dosing form and that such administration “did not result in adverse findings” (Selecta, p. 45, par. 2). Thus, a person having ordinary skill in the art could have easily arrived at a modification of Selecta’s methods such that the administration period is extended to “monthly for at least six months”. This modification would have predictably improved the treatment regimen and would have been guided by factors such as the pharmacokinetics of the administered compositions.
And to the extent that applicant has argued unexpected results, it is noted that claims 1, 3 and 4 are generic methods which do not require any particular effect. Claim 2 requires “preventing gout flare” (in this case, chronic refractory gout) and therefore it would have been particularly advantageous to maintain a therapy such as by administering monthly for at least six months because Selecta’s patients include patients having gout flares in the last six months (p. 69, 7.1(4)(b)). Additionally, applicant must show that “the differences in results are in fact unexpected and unobvious and of both statistical and practical significance” (MPEP § 716.02(b)). With respect to the cited COMPARE study, both the Examiner and Applicant have agreed previously in prosecution that pegloticase and pegadricase are distinct enzymes (see the previous Non-Final Rejection at p. 5, par. 5 and p. 7, par. 2). The obviousness analysis does not depend on whether pegloticase is unexpectedly superior to an unrelated enzyme (pegadricase). Instead, the question is whether applicant’s findings are unexpected based on Selecta in view of Guttman (and, more broadly, the art as a whole). And to the extent that such a comparison is relevant, applicant’s arguments demonstrate that the allegedly unexpected result is not of statistical significance by stating “[i]n month 6, a numerical difference in responders treated with SEL-212 (54.2%) versus pegloticase (47.1%) was observed (p=0.179)” (Remarks, p. 11, par. 4). This is further shown by applicant’s statements that the claimed methods “may offer a substantial reduction in treatment burden”, “[achieved] similar or improved efficacy outcomes compared with pegloticase, despite reduced glucocorticoid use”, and “there was a trend towards better achievement of SU <6 mg/dl” (Remarks, p. 12, par. 1). Thus, applicant’s arguments contradict the assertion of unexpected results because they have not met the burden of establishing statistical significance or practical significance and, at best, show that Selecta’s composition is comparable or slightly superior over the recite time frame.
In fact, the only statistical difference demonstrated by applicant is during month 3 (Remarks, p. 11, par. 4) and when comparing the administered compound to placebo (Remarks, p. 12, par. 2 through p. 13, par. 1). Statistical difference in month 3 is not probative of unexpected results in this case because it is outside the claimed range of “at least 6 months” and it is not unexpected that Selecta’s composition would perform statistically better than placebo because Selecta teaches its usefulness to prevent gout flare and the placebo group would not have had any therapy.
Assuming, arguendo, that applicant’s position on unexpected results was compelling, they would need to demonstrate this unexpected result across a representative number of patient populations covered by “> 7 mg/dL” because they have simultaneously argued that differences in patient populations as small as 1 mg/dL can cause Selecta’s methods to be unpredictable (Remarks, p. 10, par. 3).
With respect to the third argument, as discussed in the previous response to applicant’s arguments, "[a]ny judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper." (MPEP § 2145(X)(A)). Specifically, it is appropriate to examine the prior art for teachings of the allegedly distinct patient populations to determine if it would have been obvious to have modified the Selecta Biosciences disclosure in order to arrive at the presently claimed method. As discussed in the rejection of record, Selecta Biosciences disclosed the SEL-212 therapy prior to the effective filing date of the claimed invention and Guttmann taught that chronic refractory gout encompassed patients having three or more gout flares within the past 18 months and/or having a history of inter-flare intervals of one week or less. In light of both of these pre-filing disclosures, a person having ordinary skill in the art would have immediately understood patients having three or more gout flares within the past 18 months and/or having a history of inter-flare intervals of one week or less as being treatable by the SEL-212 therapy. Accordingly, although the prior art search and rejection of record required some consideration of the content of the instant claims and disclosure, neither was relied upon in order to arrive at the rejection of record. Therefore, there was no improper hindsight required to arrive at the determination of obviousness.
For at least these reasons, the rejection of record is proper and must be maintained. However, in the interest of addressing applicant’s amendments to the claims, the rejection of record is withdrawn and a new ground of rejection is made below.
New grounds of rejection under 35 U.S.C. § 103
Claims 1, 3-4, 7, 20, 24, 28, 35, 39, 58, and 68-69 are rejected under 35 U.S.C. 103 as being unpatentable over Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120) in view of Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388).
Selecta Biosciences (hereinafter Selecta) is a protocol for an open label multiple dose study of a combination drug (SEL-212) combined with an open label multiple dose study of a single drug (SEL-037)(p. 5, “Methodology”). SEL-212 is a combination of SEL-037 and SEL-110 (p. 4, “Name of Investigational Products”; p. 39, “Investigational product”). SEL-037 is recombinant pegylated Candida Urate Oxidase, also known as pegsiticase (p. 4, “Name of Active Ingredient”; p. 39, “Investigational product”). Pegsiticase is considered to be equivalent with pegadricase. This position is supported by applicant’s disclosure that “pegadricase and pegsiticase are used interchangeably” (Specification, p. 9, line 18). SEL-110 is a nanoparticle composed of PLA and PLA-PEG encapsulated rapamycin (p. 4, “Name of Active Ingredient”; p. 39, “Investigational product”). Therefore, for the purpose of applying prior art, Selecta’s use of the term “SEL-110” is considered to be equivalent with a composition comprising synthetic nanocarriers comprising rapamycin, “SEL-037” or “pegsiticase” is considered to be equivalent with a composition comprising pegadricase, and “SEL-212” is considered to be equivalent with a composition comprising SEL-110 and SEL-037.
Regarding claim 1, Selecta teaches a method of administering SEL-212. Selecta teaches that SEL-212 is the combination (i.e., the co-administration) of SEL-110 (a composition comprising synthetic nanocarriers comprising rapamycin) and SEL-037 (a composition comprising pegadricase)(Section 4.1, “Investigational Product).
With respect to the requirement that the subject has symptomatic chronic refractory gout, Selecta teaches that SEL-037 can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(Section 4.1, “Investigational Product). Selecta further teaches that the included patients are those having established or symptomatic gout. Accordingly, Selecta teaches patients having symptomatic chronic refractory gout.
With respect to the requirement that at the time of the initial co-administration, the subject is a subject having symptomatic chronic gout inadequately controlled with a xanthine oxidase inhibitor and a serum uric acid level of > 7 mg/dl, Selecta teaches that the inclusion criteria for patients receiving the SEL-212 therapy have a serum uric acid ≥ 6 mg/dL with established or symptomatic gout (Section 4.6, “Study Population”; Section 7.1, “Subject Inclusion Criteria”). The serum uric acid range disclosed by Selecta (≥ 6 mg/dl) encompasses applicant’s claimed range (>7 mg/dl). 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).
And although Selecta does not explicitly teach a patient population which has gout inadequately controlled with a xanthine oxidase inhibitor, it teaches that one of the conventional lines of therapy are “xanthine oxidase inhibitors that inhibit uric acid production” (Section 4.2.1., “Hyperuricemia”) and teaches that the SEL-037 uricase is developed “to reduce hyperuricemia in chronic gout patients refractory to conventional therapy” (Section 4.1., “Investigational product”). As such, Selecta either teaches or renders obvious the administration of “a composition comprising pegadricase” for treatment of patients with gout inadequately controlled with a xanthine oxidase inhibitor because Selecta teaches xanthine oxidase inhibitors are conventional care and teaches that the instantly claimed composition is useful for patients not controlled by such therapies.
With respect to the requirement that the composition comprising synthetic nanocarriers is administered prior to the composition comprising pegadricase with each co-administration, Section 6.1 of Selecta details the study design. Specifically, this section teaches that the SEL-212 groups receive an infusion of SEL-110 (i.e., the composition comprising synthetic nanocarriers) for 55 minutes followed by an infusion of SEL-037 (i.e., the composition comprising pegadricase) ± 3 minutes after the SEL-110 infusion and this is the same for every treatment period (p. 62-66). As such, Selecta teaches sequential co-administration of the composition comprising synthetic nanocarriers prior to the composition comprising pegadricase with each co-administration, and wherein the composition comprising pegadricase is administered within one hour of administering the composition comprising synthetic nanocarriers with each co-administration.
With respect to the requirement that the subject has three or more gout flares within the past 18 months and/or has a history of inter-flare intervals of one week or less, Selecta teaches that the method is for patients who are experiencing chronic refractory gout but is silent as to these specific patient characteristics.
Nonetheless, Guttmann et al. (hereinafter Guttmann) discusses the use of recombinant uricases for treating refractory gout (abstract). Guttmann specifically teaches that the incidence of refractory gout is believed to have increased (p. 379, left col., par. 1). Additionally, Guttmann teaches that treatment of refractory gout poses a therapeutic challenge and has thus become an area of focus in recent years (p. 379, right col., par. 2). An exemplary refractory gout treatment involves the use of pegloticase (a recombinant pegylated uricase) for “gout refractory to conventional therapy” and “patients who have failed to normalize serum uric acid” (p. 380, left col., par. 1). Guttmann defines refractory gout as including patients with three or more flares in the previous 18 months (p. 381, right col., par. 2).
Since Selecta teaches that SEL-037 (i.e., pegadricase) is useful when used in chronic refractory gout patients, and Guttmann teaches example studies wherein a recombinant uricase was administered to for chronic refractory gout in patients having three or more flares in the previous 18 months, it would have been obvious to have modified the method of administering rapamycin and pegadricase taught by Selecta such that the patients having chronic refractory gout are defined by having three or more flares in the previous 18 months. There would have been a reasonable expectation of success because both Selected and Guttmann teach that refractory gout can be treated by pegylated uricases and the modification would ensure that subjects with chronic refractory gout are properly identified for treatment. This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
With respect to the new limitation that the sequential co-administration is monthly for at least six months, a person having ordinary skill in the art could have arrived at this regimen as a result of routinely optimizing Selecta’s methods. An ordinary artisan would have been prompted to perform this experimentation in order to ensure long-term suppression of gout flare. It would have been particularly advantageous to arrive at six months because Selecta’s patient populations include patients who have had ”1 gout flare within the last 6 months” (p. 69, Section 7.1(4)(b)). And there would have been a reasonable expectation of success because Selecta teaches that SEL-212 could be administered once monthly in repeated dosing form and that such administration “did not result in adverse findings” (Selecta, p. 45, par. 2). There is no evidence that this modification is critical or elicits an unexpected or remarkable result.
Thus, claim 1 is obvious over Selecta in view of Guttmann.
Regarding claim 3, Selecta teaches a method of administering SEL-212. Selecta teaches that SEL-212 is the combination (i.e., the co-administration) of SEL-110 (a composition comprising synthetic nanocarriers comprising rapamycin) and SEL-037 (a composition comprising pegadricase)(Section 4.1, “Investigational Product).
With respect to the requirement that the subject has symptomatic chronic refractory gout, Selecta teaches that SEL-037 can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(Section 4.1, “Investigational Product). Selecta further teaches that the included patients are those having established or symptomatic gout. Accordingly, Selecta teaches patients having symptomatic chronic refractory gout.
With respect to the requirement that at the time of the initial co-administration, the subject is a subject having symptomatic chronic gout inadequately controlled with a xanthine oxidase inhibitor and a serum uric acid level of > 7 mg/dl, Selecta teaches that the inclusion criteria for patients receiving the SEL-212 therapy have a serum uric acid ≥ 6 mg/dL with established or symptomatic gout (Section 4.6, “Study Population”; Section 7.1, “Subject Inclusion Criteria”). The serum uric acid range disclosed by Selecta (≥ 6 mg/dl) encompasses applicant’s claimed range (>7 mg/dl). 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).
And although Selecta does not explicitly teach a patient population which has gout inadequately controlled with a xanthine oxidase inhibitor, it teaches that one of the conventional lines of therapy are “xanthine oxidase inhibitors that inhibit uric acid production” (Section 4.2.1., “Hyperuricemia”) and teaches that the SEL-037 uricase is developed “to reduce hyperuricemia in chronic gout patients refractory to conventional therapy” (Section 4.1., “Investigational product”). As such, Selecta either teaches or renders obvious the administration of “a composition comprising pegadricase” for treatment of patients with gout inadequately controlled with a xanthine oxidase inhibitor.
With respect to the requirement that the composition comprising polymeric synthetic nanocarriers comprises poly (D,L-lactide) (PLA), poly(D,L-lactide)-poly(ethylene glycol) (PLA-PEG) and rapamycin, Selecta teaches that the rapamycin component is a nanoparticle composed of PLA and PLA-PEG encapsulating rapamycin (p. 4, “Name of Active Ingredient”; Section 4.1, “Investigational product”) and teaches that this nanoparticle (i.e., nanocarrier) is synthetic and polymeric (Section 4.7, “Study Rationale”).
With respect to the doses of 0.05 mg/kg - 0.3 mg/kg rapamycin and 0.1 mg/kg - 0.5 mg/kg pegadricase, Selecta teaches doses of rapamycin ranging from 0.05 mg/kg to 0.15 mg/kg rapamycin and 0.2 mg/kg to 0.4 mg/kg pegadricase (summarized on p. 6). Therefore, the prior art teaches values which fall within the claimed ranges. See MPEP 2144.05.
With respect to the requirement that the composition comprising synthetic nanocarriers is administered prior to the composition comprising pegadricase with each co-administration, Section 6.1 of Selecta details the study design. Specifically, this section teaches that the SEL-212 groups receive an infusion of SEL-110 (i.e., the composition comprising synthetic nanocarriers) for 55 minutes followed by an infusion of SEL-037 (i.e., the composition comprising pegadricase) ± 3 minutes after the SEL-110 infusion and this is the same for every treatment period (p. 62-66). As such, Selecta teaches administration of the composition comprising synthetic nanocarriers prior to the composition comprising pegadricase with each co-administration, and wherein the composition comprising pegadricase is administered within one hour of administering the composition comprising synthetic nanocarriers with each co-administration.
With respect to the requirement that the subject has three or more gout flares within the past 18 months and/or has a history of inter-flare intervals of one week or less, Selecta is silent as to these specific patient characteristics. Nevertheless, as discussed above, Selecta teaches that the method is for patients who are experiencing chronic refractory gout.
Guttmann discusses the use of recombinant uricases for treating refractory gout (abstract). Guttmann specifically teaches that incidence of refractory gout is believed to have increased (p. 379, left col., par. 1). Additionally, Guttmann teaches that treatment of refractory gout poses a therapeutic challenge and has thus become an area of focus in recent years (p. 379, right col., par. 2). An exemplary refractory gout treatment involves the use of pegloticase (a recombinant pegylated uricase) for “gout refractory to conventional therapy” and “patients who have failed to normalize serum uric acid” (p. 380, left col., par. 1). Guttmann defines refractory gout as including patients with three or more flares in the previous 18 months (p. 381, right col., par. 2).
Since Selecta teaches that SEL-037 (i.e., pegadricase) is useful when used in chronic refractory gout patients, and Guttmann teaches example studies wherein a recombinant uricase was administered to for chronic refractory gout in patients having three or more flares in the previous 18 months, it would have been obvious to have modified the method of administering rapamycin and pegadricase taught by Selecta such that the patients having chronic refractory gout are defined by having three or more flares in the previous 18 months. There would have been a reasonable expectation of success because both Selected and Guttmann teach that refractory gout can be treated by pegylated uricases and the modification would ensure that subjects with chronic refractory gout are properly identified for treatment. This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
With respect to the new limitation that the sequential co-administration is monthly for at least six months, a person having ordinary skill in the art could have arrived at this regimen as a result of routinely optimizing Selecta’s methods. An ordinary artisan would have been prompted to perform this experimentation in order to ensure long-term suppression of gout flare. It would have been particularly advantageous to arrive at six months because Selecta’s patient populations include patients who have had ”1 gout flare within the last 6 months” (p. 69, Section 7.1(4)(b)). And there would have been a reasonable expectation of success because Selecta teaches that SEL-212 could be administered once monthly in repeated dosing form and that such administration “did not result in adverse findings” (Selecta, p. 45, par. 2). There is no evidence that this modification is critical or elicits an unexpected or remarkable result.
Thus, claim 3 is obvious over Selecta in view of Guttmann.
Regarding claim 4, Selecta teaches a method of administering SEL-212. Selecta teaches that SEL-212 is the combination (i.e., the co-administration) of SEL-110 (a composition comprising synthetic nanocarriers comprising rapamycin) and SEL-037 (a composition comprising pegadricase)(Section 4.1, “Investigational Product).
With respect to the requirement that the subject has symptomatic chronic refractory gout, Selecta teaches that SEL-037 can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(Section 4.1, “Investigational Product). Selecta further teaches that the included patients are those having established or symptomatic gout. Accordingly, Selecta teaches patients having symptomatic chronic refractory gout.
With respect to the requirement that at the time of the initial co-administration, the subject is a subject having symptomatic chronic gout inadequately controlled with a xanthine oxidase inhibitor and a serum uric acid level of > 7 mg/dl, Selecta teaches that the inclusion criteria for patients receiving the SEL-212 therapy have a serum uric acid ≥ 6 mg/dL with established or symptomatic gout (Section 4.6, “Study Population”; Section 7.1, “Subject Inclusion Criteria”). The serum uric acid range disclosed by Selecta (≥ 6 mg/dl) encompasses applicant’s claimed range (>7 mg/dl). 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).
And although Selecta does not explicitly teach a patient population which has gout inadequately controlled with a xanthine oxidase inhibitor, it teaches that one of the conventional lines of therapy are “xanthine oxidase inhibitors that inhibit uric acid production” (Section 4.2.1., “Hyperuricemia”) and teaches that the SEL-037 uricase is developed “to reduce hyperuricemia in chronic gout patients refractory to conventional therapy” (Section 4.1., “Investigational product”). As such, Selecta either teaches or renders obvious the administration of “a composition comprising pegadricase” for treatment of patients with gout inadequately controlled with a xanthine oxidase inhibitor.
With respect to the doses of 0.05 mg/kg - 0.3 mg/kg rapamycin and 0.1 mg/kg - 0.5 mg/kg pegadricase, Selecta teaches doses of rapamycin ranging from 0.05 mg/kg to 0.15 mg/kg rapamycin and 0.2 mg/kg to 0.4 mg/kg pegadricase (summarized on p. 6). Therefore, the prior art teaches values which fall within the claimed ranges. See MPEP 2144.05.
With respect to the requirement that the composition comprising synthetic nanocarriers is administered prior to the composition comprising pegadricase with each co-administration, Section 6.1 of Selecta details the study design. Specifically, this section teaches that the SEL-212 groups receive an infusion of SEL-110 (i.e., the composition comprising synthetic nanocarriers) for 55 minutes followed by an infusion of SEL-037 (i.e., the composition comprising pegadricase) ± 3 minutes after the SEL-110 infusion and this is the same for every treatment period (p. 62-66). As such, Selecta teaches administration of the composition comprising synthetic nanocarriers prior to the composition comprising pegadricase with each co-administration, and wherein the composition comprising pegadricase is administered within one hour of administering the composition comprising synthetic nanocarriers with each co-administration.
With respect to the requirement that the subject has three or more gout flares within the past 18 months and/or has a history of inter-flare intervals of one week or less, Selecta teaches that the method is for patients who are experiencing chronic refractory gout but is silent as to these specific patient characteristics.
Nonetheless, Guttmann discusses the use of recombinant uricases for treating refractory gout (abstract). Guttmann specifically teaches that the incidence of refractory gout is believed to have increased (p. 379, left col., par. 1). Additionally, Guttmann teaches that treatment of refractory gout poses a therapeutic challenge and has thus become an area of focus in recent years (p. 379, right col., par. 2). An exemplary refractory gout treatment involves the use of pegloticase (a recombinant pegylated uricase) for “gout refractory to conventional therapy” and “patients who have failed to normalize serum uric acid” (p. 380, left col., par. 1). Guttmann defines refractory gout as including patients with three or more flares in the previous 18 months (p. 381, right col., par. 2).
Since Selecta teaches that SEL-037 (i.e., pegadricase) is useful when used in chronic refractory gout patients, and Guttmann teaches example studies wherein a recombinant uricase was administered to for chronic refractory gout in patients having three or more flares in the previous 18 months, it would have been obvious to have modified the method of administering rapamycin and pegadricase taught by Selecta such that the patients having chronic refractory gout are defined by having three or more flares in the previous 18 months. There would have been a reasonable expectation of success because both Selected and Guttmann teach that refractory gout can be treated by pegylated uricases and the modification would ensure that subjects with chronic refractory gout are properly identified for treatment. This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
With respect to the new limitation that the sequential co-administration is monthly for at least six months, a person having ordinary skill in the art could have arrived at this regimen as a result of routinely optimizing Selecta’s methods. An ordinary artisan would have been prompted to perform this experimentation in order to ensure long-term suppression of gout flare. It would have been particularly advantageous to arrive at six months because Selecta’s patient populations include patients who have had ”1 gout flare within the last 6 months” (p. 69, Section 7.1(4)(b)). And there would have been a reasonable expectation of success because Selecta teaches that SEL-212 could be administered once monthly in repeated dosing form and that such administration “did not result in adverse findings” (Selecta, p. 45, par. 2). There is no evidence that this modification is critical or elicits an unexpected or remarkable result.
Thus, claim 4 is obvious over Selecta in view of Guttmann.
Regarding claim 7, as discussed above, Selecta in view of Guttmann renders obvious the method of claim 1.
And although Selecta in view of Guttmann does not explicitly teach that the subject is a subject with undesired uric acid deposits, Selecta teaches that gout is an intermittent inflammatory arthritis caused by the formation of urate crystals in joint fluid, which can cause an intensely painful joint inflammation and chronic hyperuricemia can lead to further deposition of uric acid in soft tissues, resulting in destructive arthritis and formation of tophi and renal calculi (Section 4.7, “Study Rationale”). Accordingly, it is considered that the subjects having uric acid deposits all have undesired uric acid deposits because Selecta teaches these deposits as being painful and destructive and because Selecta teaches the treatment of such deposits.
Regarding claim 20, Selecta in view of Guttmann makes obvious the method of claim 1, as discussed above. Selecta teaches that subjects in the trial are premedicated for gout flare prevention with colchicine and will continue colchicine for the remainder of their participation in the trial and will be given ibuprofen (or equivalent NSAID) if contraindicated for colchicine. If the subjects have a contraindication to colchicine and NSAID, they will not be given any premedication (p. 11, “Premedication for Gout Flare”; p. 76, “Gout Flares (Prevention and Treatment”), par. 1). Therefore, it is considered that Selecta teaches the method wherein the subject is not administered an additional therapeutic to prevent gout flare concomitantly with each sequential co-administration.
Regarding claim 24, Selecta teaches doses ranging from 0.05 mg/kg to 0.15 mg/kg of rapamycin and gives specific doses falling within this range (summarized on p. 6). Because Selecta teaches administration to human subjects, it is considered that “mg/kg” refers to the amount of compound per kilogram of patient weight. Therefore, because the prior art teaches a range which falls within the instantly claimed range, it is considered that the claim is obvious over Selecta in view of Guttmann. See MPEP 2144.05.
Regarding claim 28, Selecta teaches doses ranging from 0.2 mg/kg to 0.4 mg/kg of pegadricase and gives specific doses falling within this range (summarized on p. 6). Therefore, because the prior art teaches a range which falls within the instantly claimed range, it is considered that the claim is obvious over Selecta in view of Guttmann. See MPEP 2144.05.
Regarding claim 35, Selecta in view of Guttmann makes obvious the method of claim 1, as discussed above. Selecta teaches that rapamycin is an mTOR inhibitor (p. 54, par. 3).
Regarding claim 39, Selecta in view of Guttmann makes obvious the method of claim 1, as discussed above. Selecta teaches that this nanoparticle (i.e., nanocarrier) is synthetic and polymeric (p. 57, “Study Rationale”, par. 3).
Regarding claim 58, Selecta in view of Guttmann makes obvious the method of claim 1, as discussed above. Selecta teaches that all subjects are given premedication for gout flare prevention. Specifically, the subjects are given 1.2 mg loading dose of colchicine followed by 0.6 mg colchicine. Moreover, Selecta teaches that subjects receiving the therapy also receive fexofenadine and methylprednisolone (or equivalent; e.g., prednisone or dexamethasone)(p. 11, “Premedication for Study Drug Treatments”). Therefore, it is considered that Selecta in view of Guttmann makes obvious the method further comprising administering an additional therapeutic to the subject.
Regarding claim 68, Selecta in view of Guttmann makes obvious the method of claim 1, as discussed above. Selecta teaches that inclusion criteria for such a therapy include patients who:
Are males aged 21-75 inclusive or females aged 21-75 of non-childbearing potential;
Selecta defines childbearing potential as <6 weeks after surgical bilateral salpingooophorectomy or pre- or perimenopausal (i.e., less than 24 months of natural amenorrhea)(p. 70, item 5);
Have chronic gouty arthropathy (i.e., chronic refractory gout);
Have a serum uric acid ≥ 6 mg/dL;
Have negative serology for HIV-1/-1 and negative antibodies to hepatitis C;
Have fully recovered from any prior surgery (p. 69, “Subject Inclusion Criteria”).
Regarding claim 69, Selecta in view of Guttmann makes obvious the method of claim 1, as discussed above. Selecta teaches that such a therapy should be directed to patients who:
Do not have a history of anaphylaxis or severe allergic reactions;
Do not have a history of any allergy to pegylated products;
Are not on CYP3A4 inhibitors less than 14 days before dosing (i.e., administration);
Are not taking drugs known to interact with Rapamune (i.e., rapamycin);
Are not post-menopausal women having an initiation or change in dose of hormone-replacement therapy less than 1 month prior to screening;
Do not have uncontrolled diabetes with a baseline HbA1c ≥ 8%;
Do not have fasting glucose > 240 mg/dL;
Do not have fasting triglycerides > 500 mg/dL;
Do not have LDL > 200 mg/dL;
Do not have glucose-6-phosphate dehydrogenase deficiency;
Do not have uncontrolled hypertension, defined as blood pressure > 170/100 one week prior to dosing (i.e., administration);
Do not have white blood cell counts < 3.0 x 109/L;
Do not have serum aspartate aminotransferase or alanine amino transferase levels greater than three times the upper limit of normal in the absence of known active liver disease;
Do not have a glomerular filtration rate < 40 ml/min/1.73 m2;
Do not have a hemoglobin < 9 g/dL;
Do not have serum phosphate < 2.0 mg/dL;
Are not receiving ongoing treatment for arrhythmia;
Do not have history of coronary artery disease, including myocardial infarction;
Do not have congestive heart failure defined by New York Heart Association Class III or IV;
Do not have a history of hematological or autoimmune disorders;
Are not immunosuppressed or immunocompromised;
Do not have prior exposure to experimental or marketed uricase;
Has not received a live virus vaccine in the previous six months;
Do not have a history of malignancy within the last five years other than basal skin cancer (p. 69, “Subject Inclusion Criteria”; p. 69-71, “Subject Exclusion Criteria”).
Claims 1-5, 7, 20, 24, 28, 35, 39, 58, and 68-69 are rejected under 35 U.S.C. 103 as being unpatentable over Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120) in view of Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388) and Sands et al. (Annals of the Rheumatic Diseases, 2018, Vol. 77, page 658).
The teachings of Selecta and Guttmann are set forth above and applied herein. Selecta and Guttmann are found to render obvious claims 1, 3-4, 7, 20, 24, 28, 35, 39, 58, and 68-69.
Regarding claim 2, Selecta teaches a method of administering SEL-212. Selecta teaches that SEL-212 is the combination (i.e., the co-administration) of SEL-110 (a composition comprising synthetic nanocarriers comprising rapamycin) and SEL-037 (a composition comprising pegadricase)(Section 4.1, “Investigational Product).
With respect to the requirement that the subject has symptomatic chronic refractory gout, Selecta teaches that SEL-037 can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(Section 4.1, “Investigational Product). Selecta further teaches that the included patients are those having established or symptomatic gout. Accordingly, Selecta teaches patients having symptomatic chronic refractory gout.
With respect to the requirement that at the time of the initial co-administration, the subject is a subject having symptomatic chronic gout inadequately controlled with a xanthine oxidase inhibitor and a serum uric acid level of > 7 mg/dl, Selecta teaches that the inclusion criteria for patients receiving the SEL-212 therapy have a serum uric acid ≥ 6 mg/dL with established or symptomatic gout (Section 4.6, “Study Population”; Section 7.1, “Subject Inclusion Criteria”). The serum uric acid range disclosed by Selecta (≥ 6 mg/dl) encompasses applicant’s claimed range (>7 mg/dl). 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).
And although Selecta does not explicitly teach a patient population which has gout inadequately controlled with a xanthine oxidase inhibitor, it teaches that one of the conventional lines of therapy are “xanthine oxidase inhibitors that inhibit uric acid production” (Section 4.2.1., “Hyperuricemia”) and teaches that the SEL-037 uricase is developed “to reduce hyperuricemia in chronic gout patients refractory to conventional therapy” (Section 4.1., “Investigational product”). As such, Selecta either teaches or renders obvious the administration of “a composition comprising pegadricase” for treatment of patients with gout inadequately controlled with a xanthine oxidase inhibitor.
With respect to the requirement that the composition comprising synthetic nanocarriers is administered prior to the composition comprising pegadricase with each co-administration, Section 6.1 of Selecta details the study design. Specifically, this section teaches that the SEL-212 groups receive an infusion of SEL-110 (i.e., the composition comprising synthetic nanocarriers) for 55 minutes followed by an infusion of SEL-037 (i.e., the composition comprising pegadricase) ± 3 minutes after the SEL-110 infusion and this is the same for every treatment period (p. 62-66). As such, Selecta teaches administration of the composition comprising synthetic nanocarriers prior to the composition comprising pegadricase with each co-administration, and wherein the composition comprising pegadricase is administered within one hour of administering the composition comprising synthetic nanocarriers with each co-administration.
With respect to the requirement that the subject has three or more gout flares within the past 18 months and/or has a history of inter-flare intervals of one week or less, Selecta teaches that the method is for patients who are experiencing chronic refractory gout but is silent as to these specific patient characteristics.
Nonetheless, Guttmann et al. (hereinafter Guttmann) discusses the use of recombinant uricases for treating refractory gout (abstract). Guttmann specifically teaches that the incidence of refractory gout is believed to have increased (p. 379, left col., par. 1). Additionally, Guttmann teaches that treatment of refractory gout poses a therapeutic challenge and has thus become an area of focus in recent years (p. 379, right col., par. 2). An exemplary refractory gout treatment involves the use of pegloticase (a recombinant pegylated uricase) for “gout refractory to conventional therapy” and “patients who have failed to normalize serum uric acid” (p. 380, left col., par. 1). Guttmann defines refractory gout as including patients with three or more flares in the previous 18 months (p. 381, right col., par. 2).
Since Selecta teaches that SEL-037 (i.e., pegadricase) is useful when used in chronic refractory gout patients, and Guttmann teaches example studies wherein a recombinant uricase was administered to for chronic refractory gout in patients having three or more flares in the previous 18 months, it would have been obvious to have modified the method of administering rapamycin and pegadricase taught by Selecta such that the patients having chronic refractory gout are defined by having three or more flares in the previous 18 months. There would have been a reasonable expectation of success because both Selected and Guttmann teach that refractory gout can be treated by pegylated uricases and the modification would ensure that subjects with chronic refractory gout are properly identified for treatment. This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
With respect to the method being for preventing gout flare, neither Selecta nor Guttmann explicitly teach that the administration of the composition is useful for preventing gout flare.
Sands et al. (hereinafter Sands) reports the results of a phase 2 study of gout patients treated with SEL-212 (i.e., the composition comprising synthetic nanocarrier comprising rapamycin and a composition comprising pegadricase). Sands teaches SEL-212 is “designed to be the first non-immunogenic uricase therapy for refractory gout” (p. 658, “Objectives”) and patients treated with the SEL-212 composition “experienced a low rate of gout flares, with less than 25% of patients experiencing flares during the first month after treatment (p. 658, “Results”).
Therefore, since Selecta teaches the method of administering the composition and Sands teaches that administration of the composition resulted in a low rate of gout flares, with less than 25% of patients experiencing flares, it would have been obvious to have modified the method taught by Selecta to be a method of preventing gout flare. There would have been a reasonable expectation of success because Sands provides a demonstration that the composition is useful for prevention of gout flares. This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
With respect to the new limitation that the sequential co-administration is monthly for at least six months, a person having ordinary skill in the art could have arrived at this regimen as a result of routinely optimizing Selecta’s methods. An ordinary artisan would have been prompted to perform this experimentation in order to ensure long-term suppression of gout flare. It would have been particularly advantageous to arrive at six months because Selecta’s patient populations include patients who have had ”1 gout flare within the last 6 months” (p. 69, Section 7.1(4)(b)). And there would have been a reasonable expectation of success because Selecta teaches that SEL-212 could be administered once monthly in repeated dosing form and that such administration “did not result in adverse findings” (Selecta, p. 45, par. 2). There is no evidence that this modification is critical or elicits an unexpected or remarkable result.
Thus, claim 2 is obvious over Selecta in view of Guttmann and Sands.
Regarding claim 5, Selecta in view of Guttmann makes obvious the method of claim 1, as discussed above.
Neither Selecta nor Guttmann explicitly teach that the subject is identified as having had or as being expected to have gout flare from treatment with a gout therapy without concomitant administration of an additional therapeutic to prevent gout flare.
Sands teaches that 5 of 6 patients dosed with pegadricase alone developed anti-drug antibodies correlating with loss of serum uric acid control (p. 658, “Results”). Sands teaches that concomitant administration of an additional therapeutic (synthetic vaccine particle encapsulating rapamycin) resulted in sustained control of serum uric acid and, in addition, resulted in a “low rate of gout flares” (Id.).
Since Sands teaches that the combination of rapamycin and pegadricase resulted in control of serum uric acid and a low rate of gout flares, and pegadricase alone did not result in control of serum uric acid, it would have been obvious to have arrived at the method wherein the subject is expected to have gout flare from treatment with a gout therapy (pegadricase) without concomitant administration of an additional therapeutic (rapamycin) to prevent gout flare. There would have been a reasonable expectation of success because Sands directly teaches that concomitant administration of rapamycin and pegadricase prevents gout flares. This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Thus, claim 5 is obvious over Selecta in view of Guttmann and Sands.
Claims 1, 3-4, 7, 20, 24, 28, 35, 39, 53, 58, and 68-69 are rejected under 35 U.S.C. 103 as being unpatentable over Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120) in view of Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388) and Maldonado et al. (US 2014/0328854 A1; Cited in IDS filed on 02/18/2021).
The teachings of Selecta and Guttmann are set forth above and applied herein. Selecta and Guttmann are found to render obvious claims 1, 3-4, 7, 20, 24, 28, 35, 39, 58, and 68-69.
Regarding claim 53, Selecta in view of Guttmann makes obvious the method of claim 1, as discussed above. Selecta teaches the use of the rapamycin immunosuppressant in a synthetic nanocarrier but does not teach that the load is 7-12% by weight.
Maldonado et al. (hereinafter Maldonado) teaches the use of immunosuppressants attached to synthetic nanocarriers that are administered concomitantly with a therapeutic macromolecule ([0002]). Maldonado teaches that these compositions can be used to generate pharmacodynamic responses and can be administered repeatedly concomitantly to generate a desired pharmacodynamic and immunologic effect (Id.). Specifically, Maldonado teaches embodiments wherein rapamycin is the immunosuppressant ([0015], [0087], and [0161]) and teaches that exemplary enzymes include uricases ([0184]). Furthermore, Maldonado teaches that the desired pharmacodynamic effect can be reducing the production of an undesired molecule such as uric acid crystals ([0197]). It is noted that applicant defines “gout” as being a disorder or condition associated with the buildup of uric acid, such as deposition of uric crystals (specification, p. 20, lines 26-28). Finally, Maldonado teaches that the load of immunosuppressant should on average be 0.1% to 50%, or 0.1% to 20% ([0017]).
Since Maldonado teaches that the acceptable load of immunosuppressant should be 0.1-50% or 0.1-20% in therapies involving nanoparticle loaded rapamycin, it would have been obvious to have formulated the composition such that the rapamycin is loaded between 7-12% (a range falling entirely within the range disclosed by Maldonado). There would have been a reasonable expectation of success because Maldonado teaches that a broad range (0.1-50%) is acceptable for the load of rapamycin, and such a composition can be combined with a uricase for the purpose of reducing uric acid crystals (i.e., reducing gout). This obviousness is based upon the “Some Teachings, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Thus, claim 53 is considered to be obvious over Selecta in view of Guttmann and Maldonado.
Claims 1, 3-4, 7, 20, 24, 28, 35, 39, 58, 68-69, and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120) in view of Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388) and Penn Medicine (https://www.pennmedicine.org/for-patients-and-visitors/find-a-program-or-service/rheumatology/crystal-arthropathies-including-gout, webpage, accessed March 2023).
The teachings of Selecta and Guttmann are set forth above and applied herein. Selecta and Guttmann are found to render obvious claims 1, 3-4, 7, 20, 24, 28, 35, 39, 58, and 68-69.
Regarding claim 72, Selecta in view of Guttmann makes obvious the method of claim 58, as discussed above. Selecta teaches that the additional therapeutic is fexofenadine, methylprednisolone, or prednisone (p. 11, “Premedication for Study Drug Treatment”). Selecta teaches that the fexofenadine is administered 12 ± 2 hours prior to receiving the therapy and 2 ± 1 hours prior to receiving the therapy (Id.). Furthermore, methylprednisolone is administered to the subject 1 ± 0.5 hours before receiving the therapy (Id.).
Neither Selecta nor Guttmann teach the subjects are also administered prednisone 24 (±12) hours prior to the concomitant administration.
Penn Medicine reviews gout symptoms, diagnosis, and treatments. Penn Medicine teaches that oral steroid such as prednisone can relieve severe flairs and “the pain of acute gout often goes away within 24 hours of starting treatment” (p. 2). Prednisone can be prescribed for patients with several attacks (i.e., chronic gout), gouty arthritis, or uric acid kidney stones (Id.).
Since Selecta teaches an administration method for treating gout (the “base” method) and Penn Medicine teaches the technique of administering prednisone to treat severe gout flares and pain of acute gout (“a known technique”), it would have been obvious to have applied the known technique to the base method which was ready for improvement. A person having ordinary skill in the art would have recognized that the application of the known technique would have yielded predictable results and resulted in an improved system because Penn Medicine teaches that physicians prescribe this additional therapeutic to treat gout and Selecta teaches the use of steroids such as prednisone to pre-medicate patients (p. 75, “Premedication with Antihistamines and Steroids”). It would have been further obvious to have administered prednisone 24 (±12) hours prior to the concomitant administration because Penn Medicine teaches that this is the time frame which typically results in resolving gout pain (p. 2). This obviousness is based upon the “Applying a Known Technique to a Known Device (Method, or Product) Ready for Improvement To Yield Predictable Results” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007).
Thus, claim 72 is considered to be obvious over Selecta in view of Guttmann and Penn Medicine.
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.
Previous Double Patenting Rejections
Response to Applicant’s Arguments
Applicant has argued that the office “has not established that the claims of the instant application are anticipated or rendered obvious by the claims of the…referenced patents or patent applications” (Remarks, p. 16). The Examiner disagrees with this argument because the rejections of record detail the ways in which the instant claims are unpatentable over the reference patents and applications. If applicant disagrees, submission of specific argument regarding patentability of claims over the reference claims is recommended.
Additionally, applicant has argued that the rejections are improper because they have “relied on numerous secondary references” (Remarks, p. 17, par. 2). There is no prohibition on using secondary references in double patenting rejections and there is similarly no limit on secondary references needed to demonstrate obviousness. Reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention (MPEP § 2145(V)). The only relevant question is whether a person having ordinary skill in the art, at the time of filing, would have recognized the obviousness of the claimed invention. For at least the reasons discussed in the rejections and provisional rejections of record, the claims are not unpatentable for nonstatutory double patenting.
For at least these reasons, the rejections must be maintained. However, in the interest of addressing applicant’s amendments to the claims, the rejection of record is withdrawn and a new ground of rejection is made below.
It is noted that application 16/893,153 has issued as U.S. patent 12,553,041. Accordingly, the provisional rejection over this application has converted to a rejection over the published patent.
New ground of rejection for Double Patenting
Claims 1-5, 7, 20, 24, 28, 35, 39, 58, and 68-69 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,426,451 B2 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120) and Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388).
The claims of the ‘451 patent are directed to methods and compositions comprising a concomitantly administered composition comprising rapamycin (claim 11) and pegadricase. The instant claims are generic to the claims of ‘451 because they do not also recite the use of an anti-inflammatory therapeutic such as a colchicine or ibuprofen. However, Selecta teaches the use of an anti-inflammatory with the rapamycin and pegadricase (p. 11, “Premedication for Gout Flare”; p. 76, “Gout Flares (Prevention and Treatment”), par. 1). And although the claims of ‘451 further differ because they do not explicitly recite the characteristics of the patient populations, such as those recited in elements (a)-(b) of claims 1-4 and 68-69, Selecta teaches that SEL-037 can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(p. 39, “Investigational product”, par. 2). And although Selecta does not define the chronic refractory gout, as claimed, Guttmann teaches that pegylated uricases can be used in “gout refractory to conventional therapy” including patients who have had three or more gout flares within the past 18 months (p. 380, left col., par. 1; p. 381, right col., par. 2). Thus, it would be obvious for the chronic refractory gout subjects to have the claimed characteristics.
Selecta further teaches the inclusion and exclusion criteria (recited in claims 68-69, respectively)(p. 69, “Subject Inclusion Criteria”; p. 69-71, “Subject Exclusion Criteria”).
With respect to the requirement that the subject has symptomatic chronic refractory gout although the copending claims do not specifically teach this element, Selecta teaches that SEL-037 can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(p. 39, “Investigational product”, par. 2). Selecta further teaches that the included patients are those having established or symptomatic gout. Accordingly, Selecta teaches patients having symptomatic chronic refractory gout.
With respect to the requirement that the subject has a serum uric acid level of > 7 mg/dL, although the copending claims do not specifically teach this element, Selecta teaches that the inclusion criteria for patients receiving the SL-037 therapy have a serum uric acid ≥ 6 mg/dL with established or symptomatic gout (p. 7, “Inclusion Criteria”). The serum uric acid range disclosed by Selecta (≥ 6) encompasses applicant’s claimed range (>7). 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).
Thus, it would have been obvious to have arrived at the method wherein the subject has symptomatic chronic refractory gout and a serum uric acid level of > 7 mg/dL.
Finally, although the instant claims require sequential co-administration, Selecta also teaches the sequential administration of the same composition. Thus, it would have been obvious for ‘451’s concomitant administration to be a sequential co-administration.
With respect to the new limitation that the sequential co-administration is monthly for at least six months, a person having ordinary skill in the art could have arrived at this dosing regimen as a result of routinely optimizing Selecta’s methods. An ordinary artisan would have been prompted to perform this experimentation in order to ensure long-term suppression of gout flare. It would have been particularly advantageous to arrive at six months because Selecta’s patient populations include patients who have had ”1 gout flare within the last 6 months” (p. 69, Section 7.1(4)(b)). And there would have been a reasonable expectation of success because Selecta teaches that SEL-212 could be administered once monthly in repeated dosing form and that such administration “did not result in adverse findings” (Selecta, p. 45, par. 2). There is no evidence that this modification is critical or elicits an unexpected or remarkable result.
Claims 1-5, 7, 20, 24, 28, 35, 39, 53, 58, and 68-69 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,426,451 B2 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120), Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388), and Maldonado et al. (US 2014/0328854 A1; Cited in IDS filed on 02/18/2021).
The teachings of ‘451, Selecta, and Guttmann are set forth above and applied herein.
Regarding claim 53, Selecta teaches the use of the rapamycin immunosuppressant in a synthetic nanocarrier but does not teach that the load is 7-12% by weight.
Maldonado teaches the use of immunosuppressants attached to synthetic nanocarriers that are administered concomitantly with a therapeutic macromolecule ([0002]). Maldonado teaches that these compositions can be used to generate pharmacodynamic responses and can be administered repeatedly concomitantly to generate a desired pharmacodynamic and immunologic effect (Id.). Specifically, Maldonado teaches embodiments wherein rapamycin is the immunosuppressant ([0015], [0087], and [0161]) and teaches that exemplary enzymes include uricases ([0184]). Furthermore, Maldonado teaches that the desired pharmacodynamic effect can be reducing the production of an undesired molecule such as uric acid crystals ([0197]). It is noted that applicant defines “gout” as being a disorder or condition associated with the buildup of uric acid, such as deposition of uric crystals (specification, p. 20, lines 26-28). Finally, Maldonado teaches that the load of immunosuppressant should on average be 0.1% to 50%, or 0.1% to 20% ([0017]).
Since Maldonado teaches that the acceptable load of immunosuppressant should be 0.1-50% or 0.1-20% in therapies involving nanoparticle loaded rapamycin, it would have been obvious to have formulated the composition such that the rapamycin is loaded between 7-12% (a range falling entirely within the range disclosed by Maldonado).
Thus, claim 53 is considered to be unpatentable over ‘451, Selecta, and Guttmann further in view of Maldonado.
Claims 1-5, 7, 20, 24, 28, 35, 39, 58, 68-69, and 72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,426,451 B2 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120), Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388), and Penn Medicine (https://www.pennmedicine.org/for-patients-and-visitors/find-a-program-or-service/rheumatology/crystal-arthropathies-including-gout, webpage, accessed March 2023).
The teachings of ‘451, Selecta, and Guttmann are set forth above and applied herein.
Regarding claim 72, Selecta teaches that the fexofenadine is administered 12 ± 2 hours prior to receiving the therapy and 2 ± 1 hours prior to receiving the therapy (Id.). Furthermore, methylprednisolone is administered to the subject 1 ± 0.5 hours before receiving the therapy (Id.).
Selecta does not teach the subjects are also administered prednisone 24 (±12) hours prior to the concomitant administration.
Penn Medicine reviews gout symptoms, diagnosis, and treatments. Penn Medicine teaches that oral steroid such as prednisone can relieve severe flairs and “the pain of acute gout often goes away within 24 hours of starting treatment” (p. 2). Prednisone can be prescribed for patients with several attacks (i.e., chronic gout), gouty arthritis, or uric acid kidney stones (Id.).
Since Selecta teaches an administration method for treating gout and Penn Medicine teaches the technique of administering prednisone to treat severe gout flares and pain of acute gout, it would have been obvious to have administered prednisone 24 (±12) hours prior to the concomitant administration because Penn Medicine teaches that this is the time frame which typically results in resolving gout pain (p. 2).
Claims 1-5, 7, 20, 24, 28, 35, 39, 58, and 68-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12,553,041 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120) and Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388).
The claims of the ‘041 patent are directed to methods comprising the sequential co-administration of a composition comprising synthetic nanocarriers comprising PLA, PLA-PEG, and rapamycin and a composition comprising pegsiticase. Although the claims of ‘041 differ because they do not explicitly recite the characteristics of the patient populations, such as those recited in elements (a)-(b) of claims 1-4 and 68-69, Selecta teaches that SEL-037 can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(p. 39, “Investigational product”, par. 2). And although Selecta does not define the chronic refractory gout, as claimed, Guttmann teaches that pegylated uricases can be used in “gout refractory to conventional therapy” including “patients who have failed to normalize serum uric acid” and who have “three or more gout flares within the past 18 months” (p. 380, left col., par. 1; p. 381, right col., par. 2). Thus, it would be obvious for the chronic refractory gout subjects to have the claimed characteristics.
Selecta further teaches the inclusion and exclusion criteria (recited in claims 68-69, respectively)(p. 69, “Subject Inclusion Criteria”; p. 69-71, “Subject Exclusion Criteria”).
Regarding the “method of preventing gout flare” recited in claim 2, claim 4 of ‘041 teaches “a method of preventing gout flare” using the same composition.
With respect to the requirement that the subject has symptomatic chronic refractory gout, although the copending claims do not specifically teach this element, Selecta teaches that SEL-037 can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(p. 39, “Investigational product”, par. 2). Selecta further teaches that the included patients are those having established or symptomatic gout. Accordingly, Selecta teaches patients having symptomatic chronic refractory gout.
With respect to the requirement that the subject has a serum uric acid level of > 7 mg/dL although the copending claims do not specifically teach this element, Selecta teaches that the inclusion criteria for patients receiving the SL-037 therapy have a serum uric acid ≥ 6 mg/dL with established or symptomatic gout (p. 7, “Inclusion Criteria”). The serum uric acid range disclosed by Selecta (≥ 6) encompasses applicant’s claimed range (>7). 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).
Thus, it would have been obvious to have arrived at the method wherein the subject has symptomatic chronic refractory gout and a serum uric acid level of > 7 mg/dL.
With respect to the new limitation that the sequential co-administration is monthly for at least six months, a person having ordinary skill in the art could have arrived at this dosing regimen as a result of routinely optimizing Selecta’s methods. An ordinary artisan would have been prompted to perform this experimentation in order to ensure long-term suppression of gout flare. It would have been particularly advantageous to arrive at six months because Selecta’s patient populations include patients who have had ”1 gout flare within the last 6 months” (p. 69, Section 7.1(4)(b)). And there would have been a reasonable expectation of success because Selecta teaches that SEL-212 could be administered once monthly in repeated dosing form and that such administration “did not result in adverse findings” (Selecta, p. 45, par. 2). There is no evidence that this modification is critical or elicits an unexpected or remarkable result.
Thus, the claims of the instant application are obvious over ‘041 in view of Selecta and Guttmann.
Claims 1-5, 7, 20, 24, 28, 30, 35, 39, 53, 58, and 68-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 U.S. Patent No. 12,553,041 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120), Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388), and Maldonado et al. (US 2014/0328854 A1; Cited in IDS filed on 02/18/2021).
The teachings of ‘041, Selecta, and Guttmann are set forth above and applied herein.
Regarding claim 53, Selecta teaches the use of the rapamycin immunosuppressant in a synthetic nanocarrier but does not teach that the load is 7-12% by weight.
Maldonado teaches the use of immunosuppressants attached to synthetic nanocarriers that are administered concomitantly with a therapeutic macromolecule ([0002]). Maldonado teaches that these compositions can be used to generate pharmacodynamic responses and can be administered repeatedly concomitantly to generate a desired pharmacodynamic and immunologic effect (Id.). Specifically, Maldonado teaches embodiments wherein rapamycin is the immunosuppressant ([0015], [0087], and [0161]) and teaches that exemplary enzymes include uricases ([0184]). Furthermore, Maldonado teaches that the desired pharmacodynamic effect can be reducing the production of an undesired molecule such as uric acid crystals ([0197]). It is noted that applicant defines “gout” as being a disorder or condition associated with the buildup of uric acid, such as deposition of uric crystals (specification, p. 20, lines 26-28). Finally, Maldonado teaches that the load of immunosuppressant should on average be 0.1% to 50%, or 0.1% to 20% ([0017]).
Since Maldonado teaches that the acceptable load of immunosuppressant should be 0.1-50% or 0.1-20% in therapies involving nanoparticle loaded rapamycin, it would have been obvious to have formulated the composition such that the rapamycin is loaded between 7-12% (a range falling entirely within the range disclosed by Maldonado).
Thus, claim 53 is considered to be obvious over ‘041, Selecta, and Guttmann, further in view of Maldonado.
Claims 1-5, 7, 20, 24, 28, 30, 35, 39, 58, 68-69, and 72 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12,553,041 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120), Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388), and Penn Medicine (https://www.pennmedicine.org/for-patients-and-visitors/find-a-program-or-service/rheumatology/crystal-arthropathies-including-gout, webpage, accessed March 2023).
The teachings of ‘041, Selecta, and Guttmann are set forth above and applied herein.
Regarding claim 72, Selecta teaches that the fexofenadine is administered 12 ± 2 hours prior to receiving the therapy and 2 ± 1 hours prior to receiving the therapy (Id.). Furthermore, methylprednisolone is administered to the subject 1 ± 0.5 hours before receiving the therapy (Id.).
Selecta does not teach the subjects are also administered prednisone 24 (±12) hours prior to the concomitant administration.
Penn Medicine reviews gout symptoms, diagnosis, and treatments. Penn Medicine teaches that oral steroid such as prednisone can relieve severe flairs and “the pain of acute gout often goes away within 24 hours of starting treatment” (p. 2). Prednisone can be prescribed for patients with several attacks (i.e., chronic gout), gouty arthritis, or uric acid kidney stones (Id.).
Since Selecta teaches an administration method for treating gout and Penn Medicine teaches the technique of administering prednisone to treat severe gout flares and pain of acute gout, it would have been obvious to have administered prednisone 24 (±12) hours prior to the concomitant administration because Penn Medicine teaches that this is the time frame which typically results in resolving gout pain (p. 2).
Claims 1-5, 7, 20, 24, 28, 30, 35, 39, 58, 68-69, and 72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12,194,078 B2 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120) and Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388).
The claims of the ‘078 patent are directed to methods concomitantly administering a composition comprising rapamycin and pegadricase. The instant claims are generic to the copending claims because they do not also recite the use of an anti-inflammatory therapeutic such as an NSAID. However, Selecta teaches the use of an NSAID with the rapamycin and pegadricase (p. 11, “Premedication for Gout Flare”; p. 76, “Gout Flares (Prevention and Treatment”), par. 1). Although the claims of ‘078 differ because they do not explicitly recite the characteristics of the patient populations, such as those recited in elements (a)-(b) of claims 1-4 and 68-69, Selecta teaches that SEL-037 can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(p. 39, “Investigational product”, par. 2). Although Selecta does not define the chronic refractory gout, as claimed, Guttmann teaches that pegylated uricases can be used in “gout refractory to conventional therapy” including “patients who have failed to normalize serum uric acid” and who have “three or more gout flares within the past 18 months” (p. 380, left col., par. 1; p. 381, right col., par. 2). Thus, it would be obvious for the chronic refractory gout subjects to have the claimed characteristics.
With respect to the requirement that the subject has symptomatic chronic refractory gout, although the copending claims do not specifically teach this element, Selecta teaches that SEL-037 can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(p. 39, “Investigational product”, par. 2). Selecta further teaches that the included patients are those having established or symptomatic gout. Accordingly, Selecta teaches patients having symptomatic chronic refractory gout.
With respect to the requirement that the subject has a serum uric acid level of > 7 mg/dL although ‘078’s claims do not specifically teach this element, Selecta teaches that the inclusion criteria for patients receiving the SL-037 therapy have a serum uric acid ≥ 6 mg/dL with established or symptomatic gout (p. 7, “Inclusion Criteria”). The serum uric acid range disclosed by Selecta (≥ 6) encompasses applicant’s claimed range (>7). 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).
Thus, it would have been obvious to have arrived at the method wherein the subject has symptomatic chronic refractory gout and a serum uric acid level of > 7 mg/dL.
Selecta further teaches the inclusion and exclusion criteria (recited in claims 68-69, respectively)(p. 69, “Subject Inclusion Criteria”; p. 69-71, “Subject Exclusion Criteria”).
Claims 9-13 of the ‘078 patent are directed to additional therapeutics and their timeframes of administration. Claims 9-10 recite fexofenadine, prednisone and methylprednisolone and teach that they are administered within 24 hours. Thus, claim 72 of the instant application is considered to be obvious over this teaching.
Finally, although the instant claims require sequential co-administration, Selecta also teaches the sequential administration of the same composition. Thus, it would have been obvious for ‘078’s concomitant administration to be a sequential co-administration.
With respect to the new limitation that the sequential co-administration is monthly for at least six months, a person having ordinary skill in the art could have arrived at this dosing regimen as a result of routinely optimizing Selecta’s methods. An ordinary artisan would have been prompted to perform this experimentation in order to ensure long-term suppression of gout flare. It would have been particularly advantageous to arrive at six months because Selecta’s patient populations include patients who have had ”1 gout flare within the last 6 months” (p. 69, Section 7.1(4)(b)). And there would have been a reasonable expectation of success because Selecta teaches that SEL-212 could be administered once monthly in repeated dosing form and that such administration “did not result in adverse findings” (Selecta, p. 45, par. 2). There is no evidence that this modification is critical or elicits an unexpected or remarkable result.
Claims 1-5, 7, 20, 24, 28, 30, 35, 39, 53, 58, 68-69, and 72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 U.S. Patent No. 12,194,078 B2 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120), Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388), and Maldonado et al. (US 2014/0328854 A1; Cited in IDS filed on 02/18/2021).
The teachings of ‘073, Selecta, and Guttmann are set forth above and applied herein.
Regarding claim 53, Selecta teaches the use of the rapamycin immunosuppressant in a synthetic nanocarrier but does not teach that the load is 7-12% by weight.
Maldonado teaches the use of immunosuppressants attached to synthetic nanocarriers that are administered concomitantly with a therapeutic macromolecule ([0002]). Maldonado teaches that these compositions can be used to generate pharmacodynamic responses and can be administered repeatedly concomitantly to generate a desired pharmacodynamic and immunologic effect (Id.). Specifically, Maldonado teaches embodiments wherein rapamycin is the immunosuppressant ([0015], [0087], and [0161]) and teaches that exemplary enzymes include uricases ([0184]). Furthermore, Maldonado teaches that the desired pharmacodynamic effect can be reducing the production of an undesired molecule such as uric acid crystals ([0197]). It is noted that applicant defines “gout” as being a disorder or condition associated with the buildup of uric acid, such as deposition of uric crystals (specification, p. 20, lines 26-28). Finally, Maldonado teaches that the load of immunosuppressant should on average be 0.1% to 50%, or 0.1% to 20% ([0017]).
Since Maldonado teaches that the acceptable load of immunosuppressant should be 0.1-50% or 0.1-20% in therapies involving nanoparticle loaded rapamycin, it would have been obvious to have formulated the composition such that the rapamycin is loaded between 7-12% (a range falling entirely within the range disclosed by Maldonado).
Thus, claim 53 is considered to be obvious over ‘073, Selecta, and Guttmann, further in view of Maldonado.
Claims 1, 3-5, 7, 20, 24, 28, 30, 35, 39, 58, and 68-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 116-135 of copending Application No. 18/818,714 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120) and Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388).
The claims of the copending application are directed to methods comprising the concomitant administration of a composition comprising synthetic nanocarriers comprising PLA, PLA-PEG, and rapamycin and a composition comprising pegsiticase. In an embodiment, the composition is administered to a subject identified as having had or as being expected to have gout flare. Although the claims of ‘714 differ because they do not explicitly recite the characteristics of the patient populations, such as those recited in elements (a)-(b) of claims 1-4 and 68-69, Selecta teaches that SEL-037 can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(p. 39, “Investigational product”, par. 2). Although Selecta does not define the chronic refractory gout, as claimed, Guttmann teaches that pegylated uricases can be used in “gout refractory to conventional therapy” including “patients who have failed to normalize serum uric acid” and who have “three or more gout flares within the past 18 months” (p. 380, left col., par. 1; p. 381, right col., par. 2). Thus, it would be obvious for the chronic refractory gout subjects to have the claimed characteristics.
Selecta further teaches the inclusion and exclusion criteria (recited in claims 68-69, respectively)(p. 69, “Subject Inclusion Criteria”; p. 69-71, “Subject Exclusion Criteria”).
With respect to the requirement that the subject has symptomatic chronic refractory gout, although the copending claims do not specifically teach this element, Selecta teaches that SEL-037 can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(p. 39, “Investigational product”, par. 2). Selecta further teaches that the included patients are those having established or symptomatic gout. Accordingly, Selecta teaches patients having symptomatic chronic refractory gout.
With respect to the requirement that the subject has a serum uric acid level of > 7 mg/dL although the copending claims do not specifically teach this element, Selecta teaches that the inclusion criteria for patients receiving the SL-037 therapy have a serum uric acid ≥ 6 mg/dL with established or symptomatic gout (p. 7, “Inclusion Criteria”). The serum uric acid range disclosed by Selecta (≥ 6) encompasses applicant’s claimed range (>7). 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).
Thus, it would have been obvious to have arrived at the method wherein the subject has symptomatic chronic refractory gout and a serum uric acid level of > 7 mg/dL.
With respect to the new limitation that the sequential co-administration is monthly for at least six months, a person having ordinary skill in the art could have arrived at this dosing regimen as a result of routinely optimizing Selecta’s methods. An ordinary artisan would have been prompted to perform this experimentation in order to ensure long-term suppression of gout flare. It would have been particularly advantageous to arrive at six months because Selecta’s patient populations include patients who have had ”1 gout flare within the last 6 months” (p. 69, Section 7.1(4)(b)). And there would have been a reasonable expectation of success because Selecta teaches that SEL-212 could be administered once monthly in repeated dosing form and that such administration “did not result in adverse findings” (Selecta, p. 45, par. 2). There is no evidence that this modification is critical or elicits an unexpected or remarkable result.
Thus, the claims of the instant application are obvious over ‘714 in view of Selecta and Guttmann.
Claims 1-5, 7, 20, 24, 28, 30, 35, 39, 58, and 68-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 116-135 of copending Application No. 18/818,714 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120), Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388), and Sands et al. (Annals of the Rheumatic Diseases, 2018, Vol. 77, page 658).
The teachings of ‘714, Selecta, and Guttmann are set forth above and applied herein.
Regarding claim 2, although the claims of ‘714 do not teach preventing gout flare, Sands reports the results of a phase 2 study of gout patients treated with SEL-212 (i.e., the composition comprising synthetic nanocarrier comprising rapamycin and a composition comprising pegadricase). Sands teaches SEL-212 is “designed to be the first non-immunogenic uricase therapy for refractory gout” (p. 658, “Objectives”) and patients treated with the SEL-212 composition “experienced a low rate of gout flares, with less than 25% of patients experiencing flares during the first month after treatment (p. 658, “Results”).
Therefore, since ‘714 teaches the method of administering the composition and Sands teaches that administration of the composition resulted in a low rate of gout flares, with less than 25% of patients experiencing flares, it would have been obvious to have modified the method taught by Selecta to be a method of preventing gout flare. There would have been a reasonable expectation of success because Sands provides a demonstration that the composition is useful for this purpose. This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
With respect to the new limitation that the sequential co-administration is monthly for at least six months, a person having ordinary skill in the art could have arrived at this dosing regimen as a result of routinely optimizing Selecta’s methods. An ordinary artisan would have been prompted to perform this experimentation in order to ensure long-term suppression of gout flare. It would have been particularly advantageous to arrive at six months because Selecta’s patient populations include patients who have had ”1 gout flare within the last 6 months” (p. 69, Section 7.1(4)(b)). And there would have been a reasonable expectation of success because Selecta teaches that SEL-212 could be administered once monthly in repeated dosing form and that such administration “did not result in adverse findings” (Selecta, p. 45, par. 2). There is no evidence that this modification is critical or elicits an unexpected or remarkable result.
Claims 1, 3-5, 7, 20, 24, 28, 30, 35, 39, 53, 58, and 68-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 116-135 of copending Application No. 18/818,714 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120), Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388), and Maldonado et al. (US 2014/0328854 A1; Cited in IDS filed on 02/18/2021).
The teachings of ‘714, Selecta, and Guttmann are set forth above and applied herein.
Regarding claim 53, Selecta teaches the use of the rapamycin immunosuppressant in a synthetic nanocarrier but does not teach that the load is 7-12% by weight.
Maldonado teaches the use of immunosuppressants attached to synthetic nanocarriers that are administered concomitantly with a therapeutic macromolecule ([0002]). Maldonado teaches that these compositions can be used to generate pharmacodynamic responses and can be administered repeatedly concomitantly to generate a desired pharmacodynamic and immunologic effect (Id.). Specifically, Maldonado teaches embodiments wherein rapamycin is the immunosuppressant ([0015], [0087], and [0161]) and teaches that exemplary enzymes include uricases ([0184]). Furthermore, Maldonado teaches that the desired pharmacodynamic effect can be reducing the production of an undesired molecule such as uric acid crystals ([0197]). It is noted that applicant defines “gout” as being a disorder or condition associated with the buildup of uric acid, such as deposition of uric crystals (specification, p. 20, lines 26-28). Finally, Maldonado teaches that the load of immunosuppressant should on average be 0.1% to 50%, or 0.1% to 20% ([0017]).
Since Maldonado teaches that the acceptable load of immunosuppressant should be 0.1-50% or 0.1-20% in therapies involving nanoparticle loaded rapamycin, it would have been obvious to have formulated the composition such that the rapamycin is loaded between 7-12% (a range falling entirely within the range disclosed by Maldonado).
Thus, claim 53 is considered to be obvious over ‘714, Selecta, and Guttmann, further in view of Maldonado.
Claims 1, 3-5, 7, 20, 24, 28, 30, 35, 39, 58, 68-69, and 72 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 116-135 of copending Application No. 18/818,714 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120), Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388), and Penn Medicine (https://www.pennmedicine.org/for-patients-and-visitors/find-a-program-or-service/rheumatology/crystal-arthropathies-including-gout, webpage, accessed March 2023).
The teachings of ‘714, Selecta, and Guttmann are set forth above and applied herein.
Regarding claim 72, Selecta teaches that the fexofenadine is administered 12 ± 2 hours prior to receiving the therapy and 2 ± 1 hours prior to receiving the therapy (Id.). Furthermore, methylprednisolone is administered to the subject 1 ± 0.5 hours before receiving the therapy (Id.).
Selecta does not teach the subjects are also administered prednisone 24 (±12) hours prior to the concomitant administration.
Penn Medicine reviews gout symptoms, diagnosis, and treatments. Penn Medicine teaches that oral steroid such as prednisone can relieve severe flairs and “the pain of acute gout often goes away within 24 hours of starting treatment” (p. 2). Prednisone can be prescribed for patients with several attacks (i.e., chronic gout), gouty arthritis, or uric acid kidney stones (Id.).
Since Selecta teaches an administration method for treating gout and Penn Medicine teaches the technique of administering prednisone to treat severe gout flares and pain of acute gout, it would have been obvious to have administered prednisone 24 (±12) hours prior to the concomitant administration because Penn Medicine teaches that this is the time frame which typically results in resolving gout pain (p. 2).
Claims 1, 3-5, 7, 20, 24, 28, 30, 35, 39, 58, and 68-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 116, 118-120, 122-129, and 132-134 of copending Application No. 18/933,195 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120) and Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388).
The claims of the copending application are directed to methods comprising the sequential co-administration of a composition comprising synthetic nanocarriers comprising PLA, PLA-PEG, and rapamycin and a composition comprising pegsiticase. In an embodiment, the composition is administered to a subject identified as having had or as being expected to have gout flare. Although the claims of ‘195 differ because they do not explicitly recite the characteristics of the patient populations, such as those recited in elements (a)-(b) of claims 1-4 and 68-69, Selecta teaches that SEL-037 can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(p. 39, “Investigational product”, par. 2). Although Selecta does not define the chronic refractory gout, as claimed, Guttmann teaches that pegylated uricases can be used in “gout refractory to conventional therapy” including “patients who have failed to normalize serum uric acid” and who have “three or more gout flares within the past 18 months” (p. 380, left col., par. 1; p. 381, right col., par. 2). Thus, it would be obvious for the chronic refractory gout subjects to have the claimed characteristics.
Selecta further teaches the inclusion and exclusion criteria (recited in claims 68-69, respectively)(p. 69, “Subject Inclusion Criteria”; p. 69-71, “Subject Exclusion Criteria”).
With respect to the requirement that the subject has symptomatic chronic refractory gout, although the copending claims do not specifically teach this element, Selecta teaches that SEL-037 can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(p. 39, “Investigational product”, par. 2). Selecta further teaches that the included patients are those having established or symptomatic gout. Accordingly, Selecta teaches patients having symptomatic chronic refractory gout.
With respect to the requirement that the subject has a serum uric acid level of > 7 mg/dL although the copending claims do not specifically teach this element, Selecta teaches that the inclusion criteria for patients receiving the SL-037 therapy have a serum uric acid ≥ 6 mg/dL with established or symptomatic gout (p. 7, “Inclusion Criteria”). The serum uric acid range disclosed by Selecta (≥ 6) encompasses applicant’s claimed range (>7). 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).
Thus, it would have been obvious to have arrived at the method wherein the subject has symptomatic chronic refractory gout and a serum uric acid level of > 7 mg/dL.
With respect to the new limitation that the sequential co-administration is monthly for at least six months, application ‘195 teaches that the composition can be administered monthly for at least six months (claim 128).
Thus, the claims of the instant application are obvious over ‘195 in view of Selecta and Guttmann.
Claims 1-5, 7, 20, 24, 28, 30, 35, 39, 58, and 68-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 116-135 of copending Application No. 18/933,195 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120), Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388), and Sands et al. (Annals of the Rheumatic Diseases, 2018, Vol. 77, page 658).
The teachings of ‘195, Selecta, and Guttmann are set forth above and applied herein.
Regarding claim 2, although the claims of ‘195 do not teach preventing gout flare, Sands reports the results of a phase 2 study of gout patients treated with SEL-212 (i.e., the composition comprising synthetic nanocarrier comprising rapamycin and a composition comprising pegadricase). Sands teaches SEL-212 is “designed to be the first non-immunogenic uricase therapy for refractory gout” (p. 658, “Objectives”) and patients treated with the SEL-212 composition “experienced a low rate of gout flares, with less than 25% of patients experiencing flares during the first month after treatment (p. 658, “Results”).
Therefore, since ‘195 teaches the method of administering the composition and Sands teaches that administration of the composition resulted in a low rate of gout flares, with less than 25% of patients experiencing flares, it would have been obvious to have modified the method taught by Selecta to be a method of preventing gout flare. There would have been a reasonable expectation of success because Sands provides a demonstration that the composition is useful for this purpose. This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
With respect to the new limitation that the sequential co-administration is monthly for at least six months, application ‘195 teaches that the composition can be administered monthly for at least six months (claim 128).
Claims 1, 3-5, 7, 20, 24, 28, 30, 35, 39, 53, 58, and 68-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 116-135 of copending Application No. 18/933,195 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120), Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388), and Maldonado et al. (US 2014/0328854 A1; Cited in IDS filed on 02/18/2021).
The teachings of ‘195, Selecta, and Guttmann are set forth above and applied herein.
Regarding claim 53, Selecta teaches the use of the rapamycin immunosuppressant in a synthetic nanocarrier but does not teach that the load is 7-12% by weight.
Maldonado teaches the use of immunosuppressants attached to synthetic nanocarriers that are administered concomitantly with a therapeutic macromolecule ([0002]). Maldonado teaches that these compositions can be used to generate pharmacodynamic responses and can be administered repeatedly concomitantly to generate a desired pharmacodynamic and immunologic effect (Id.). Specifically, Maldonado teaches embodiments wherein rapamycin is the immunosuppressant ([0015], [0087], and [0161]) and teaches that exemplary enzymes include uricases ([0184]). Furthermore, Maldonado teaches that the desired pharmacodynamic effect can be reducing the production of an undesired molecule such as uric acid crystals ([0197]). It is noted that applicant defines “gout” as being a disorder or condition associated with the buildup of uric acid, such as deposition of uric crystals (specification, p. 20, lines 26-28). Finally, Maldonado teaches that the load of immunosuppressant should on average be 0.1% to 50%, or 0.1% to 20% ([0017]).
Since Maldonado teaches that the acceptable load of immunosuppressant should be 0.1-50% or 0.1-20% in therapies involving nanoparticle loaded rapamycin, it would have been obvious to have formulated the composition such that the rapamycin is loaded between 7-12% (a range falling entirely within the range disclosed by Maldonado).
Thus, claim 53 is considered to be obvious over ‘195, Selecta, and Guttmann, further in view of Maldonado.
Claims 1, 3-5, 7, 20, 24, 28, 30, 35, 39, 58, 68-69, and 72 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 116-135 of copending Application No. 18/933,195 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120), Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388), and Penn Medicine (https://www.pennmedicine.org/for-patients-and-visitors/find-a-program-or-service/rheumatology/crystal-arthropathies-including-gout, webpage, accessed March 2023).
The teachings of ‘195, Selecta, and Guttmann are set forth above and applied herein.
Regarding claim 72, Selecta teaches that the fexofenadine is administered 12 ± 2 hours prior to receiving the therapy and 2 ± 1 hours prior to receiving the therapy (Id.). Furthermore, methylprednisolone is administered to the subject 1 ± 0.5 hours before receiving the therapy (Id.).
Selecta does not teach the subjects are also administered prednisone 24 (±12) hours prior to the concomitant administration.
Penn Medicine reviews gout symptoms, diagnosis, and treatments. Penn Medicine teaches that oral steroid such as prednisone can relieve severe flairs and “the pain of acute gout often goes away within 24 hours of starting treatment” (p. 2). Prednisone can be prescribed for patients with several attacks (i.e., chronic gout), gouty arthritis, or uric acid kidney stones (Id.).
Since Selecta teaches an administration method for treating gout and Penn Medicine teaches the technique of administering prednisone to treat severe gout flares and pain of acute gout, it would have been obvious to have administered prednisone 24 (±12) hours prior to the concomitant administration because Penn Medicine teaches that this is the time frame which typically results in resolving gout pain (p. 2).
Claims 1-5, 7, 20, 24, 28, 30, 35, 39, 53, 58, 68-69, and 72 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50-66, 70, 81, and 83 of copending Application No. 18/828,371 in view of Selecta Biosciences (Study Protocol, SEL-212/201, 2018, Version 7.1, pages 1-120) and Guttmann et al. (Therapeutic Advances in Drug Safety, 2017, Vol. 8(12), p. 379-388).
The claims of the copending application are directed to compositions comprising synthetic nanocarriers comprising an immunosuppressant, a uricase, and an anti-inflammatory therapeutic. The instant claims are generic to the copending claims because the composition used in the instant claims does not also comprise an anti-inflammatory therapeutic such as an NSAID. However, because of the open “comprising” language of the instant claims, the composition does not exclude an anti-inflammatory and the anti-inflammatory can be considered to be the “additional therapeutic” of claim 58. Moreover, Selecta teaches the use of an NSAID with the rapamycin and pegadricase (p. 11, “Premedication for Gout Flare”; p. 76, “Gout Flares (Prevention and Treatment”), par. 1).
Although the claims of ‘371 further differ because they are not directed to a method of administering to a gout patient and do not explicitly recite the characteristics of the patient populations, such as those recited in elements (a)-(b) of claims 1-4 and 68-69, Selecta teaches that SEL-037 (a composition comprising an immunosuppressant and a uricase) can reduce hyperuricemia in chronic gout patients refractory to conventional therapy (i.e., chronic refractory gout)(p. 39, “Investigational product”, par. 2). And although Selecta does not define the chronic refractory gout, as claimed, Guttmann teaches that pegylated uricases can be used in “gout refractory to conventional therapy” including “patients who have failed to normalize serum uric acid” and “whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated” (p. 380, left col., par. 1). Selecta further teaches the inclusion and exclusion criteria (recited in claims 68-69, respectively)(p. 69, “Subject Inclusion Criteria”; p. 69-71, “Subject Exclusion Criteria”). Thus, it would have been obvious for the chronic refractory gout subjects to have the claimed characteristics, and it would have been obvious to have used the composition of ‘371 in a method of administering the composition to a subject having symptomatic chronic refractory gout.
With respect to the new limitation that the sequential co-administration is monthly for at least six months, a person having ordinary skill in the art could have arrived at this dosing regimen as a result of routinely optimizing Selecta’s methods. An ordinary artisan would have been prompted to perform this experimentation in order to ensure long-term suppression of gout flare. It would have been particularly advantageous to arrive at six months because Selecta’s patient populations include patients who have had ”1 gout flare within the last 6 months” (p. 69, Section 7.1(4)(b)). And there would have been a reasonable expectation of success because Selecta teaches that SEL-212 could be administered once monthly in repeated dosing form and that such administration “did not result in adverse findings” (Selecta, p. 45, par. 2). There is no evidence that this modification is critical or elicits an unexpected or remarkable result.
Claim 59 of ‘371 limits the immunosuppressant to be an mTOR inhibitor.
Claim 63 of ‘371 limits the synthetic nanocarriers to be polymeric synthetic nanocarriers.
Claim 81 of ‘371 limits the load of the immunosuppressant to 7-12%, which is the same amount recited in instant claim 53.
Claims 55-56 recite fexofenadine, prednisone and methylprednisolone.
Thus, because the compositions of the copending application overlap in scope with the composition used in the instantly claimed methods in view of Selecta and Guttmann, they are unpatentable over each other.
Conclusion
No claim is allowed.
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.
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/GRANT C CURRENS/Examiner, Art Unit 1651