DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Priority
The instant application claims priority to Provisional Application 61/510,268 filed July 21, 2021 and U.S. Applications 13/536,081; 14/302,730; 16/539,455; and 19/202,626 filed June 28, 2012; June 12, 2014; August 13, 2019; and May 8, 2025, respectively.
Neither Provisional Application 61/510,268 nor U.S. Applications 13/536,081; 14/302,730; 16/539,455; and 19/202,626 contemplate methods involving selecting a candidate anti-IL-31 antibody for development as a therapeutic nor advancing a candidate anti-IL-31 antibody for development.
Should Applicant disagree with the above, he or she should point to the precise page and line which provides basis for steps (d) in claims 49 and 63.
Thus, claims 39-48 and 54-62 are examined with the priority date of July 21, 2011 and claims 49-53, 63, and 64 are examined with the filing date of the instant application, February 10, 2026.
Applicant states that this application is a continuation or divisional application of the prior-filed application. A continuation or divisional application cannot include new matter. Applicant is required to delete the benefit claim or change the relationship (continuation or divisional application) to continuation-in-part because this application contains the following matter not disclosed in the prior-filed application: as above, the prior-filed applications do not contemplate methods involving selecting a candidate anti-IL-31 antibody for development as a therapeutic nor advancing a candidate anti-IL-31 antibody for development.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 39-65 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claims recite methods for evaluating the in vivo efficacy of an anti-IL-31 against pruritus comprising a) administering an anti-IL-31 antibody, b) measuring, quantifying, or quantitatively measuring pruritic behavior, c) comparing measured pruritic behavior relative to pre-administration pruritic behavior, and d) identifying an anti-IL-31 antibody as having anti-pruritic activity, identifying an anti-IL-31 antibody as having anti-pruritic activity and selecting the anti-IL-31 antibody for further development, or identifying an anti-IL-31 antibody as having anti-pruritic activity and advancing the anti-IL-31 antibody for continued development. The steps of “comparing”, and “identifying”, “identifying” and “selecting”, or “identifying” and “advancing” are mental steps or steps which are completed entirely in the mind. This judicial exception is not integrated into a practical application because the steps of “administering”, and “measuring”, “quantifying”, or “quantitatively measuring” are extra-solution activities or field-of-use. The step of “measuring”, “quantifying”, or “quantitatively measuring” is a data gathering extra-solution activity and the step of “administering” extra-solution activity or a field-of-use and does not integrate the judicial exception into a practical application; see MPEP 2106.04(d)(2)c. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not require any additional steps and the steps of “administering”, and “measuring”, “quantifying”, or “quantitatively measuring” are extra-solution activities or field-of-use and do not amount to significantly more; see MPEP 2106.05 I.A. and MPEP 2106.05(c).
Thus, claims 39-65 are rejected for reciting a judicial exception without significantly more.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 49-65 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 49 recites step (d) “selecting the candidate anti-IL-31 antibody for development as an anti-pruritic therapeutic for the treatment of atopic dermatitis” when pruritic behavior is reduced relative to baseline. It is unclear whether action is required to meet the step of “selecting […] for further development as an anti-pruritic therapeutic for the treatment of atopic dermatitis”. Selecting is defined as “choos[ing] (as by fitness or excellence) from a number or group”; see Merriam-Webster. Does “selecting […] for further development” require further action to the chosen candidate to meet the claim? The step of “selecting” appears to be a mental step. For the purpose of compact prosecution, step (d) is interpreted as identifying a candidate as having anti-pruritic activity when pruritic behavior is reduced relative to the baseline. Merriam-Webster defines identify as “to perceive or state the identity of (someone or something)” which is understood to not require further action and is a mental step. In other words, because it is unclear what is required to meet “selecting”, for the purpose of applying art, only the mental step of identifying is required.
Claims 50-53 are rejected for depending from claim 49 and failing to remedy the indefiniteness.
Claim 54 recites a method comprising step (b) wherein pruritic behavior is measured in the dog within one week of administration. Within one week of administration is understood to encompass immediately after administration to 7 days following administration. Step (d) recites the antibody has in vivo efficacy when the measured pruritic behavior is reduced relative to the baseline for at least one to two weeks. One to two weeks after administration is understood to mean 7 to 14 days after administration. It is unclear how one could measure pruritic behavior at, for example, 5 days following administration, which is “within one week”, and still be able to complete the method step (d), identifying the antibody as having or not having in vivo efficacy based on a comparison from baseline to 7 to 14 days after administration, as recited. For the purpose of compact prosecution, the claim is interpreted as requiring measuring within one week of administration and identifying an anti-IL-31 antibody as efficacious based on the comparison between baseline and the within one week measurement. Similarly, regarding claim 65, how does the measured pruritic behavior within one week of administration inform the pruritic behavior for at least 5 weeks?
Claims 55-62 and 65 are rejected for depending from claim 54 and failing to remedy the indefiniteness.
Claim 63 recites step (d) “advancing the candidate anti-IL-31 antibody for continued development”. The instant disclosure does not define or exemplify “advancing” the development of an antibody. It is unclear whether further action is required to meet the step of “advancing”. Similar to “selecting” in claim 49, “advancing” appears to be a mental step. For the purpose of compact prosecution, step (d) is interpreted as identifying a candidate as having in vivo efficacy in the treatment of atopic dermatitis when pruritic behavior score is reduced by at least 75% relative to the baseline. Merriam-Webster defines identify as “to perceive or state the identity of (someone or something)” which is understood to not require further action and is a mental step. In other words, because it is unclear what is required to meet “advancing”, for the purpose of applying art, only the mental step of identifying is required.
Claim 64 is rejected for depending from claim 63 and failing to remedy the indefiniteness.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 49-53 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Fleck et al. (Veterinary Dermatology. 32: 681-684; Published Online: April 8, 2021) in view of Steffan et al. (Journal of American Veterinary Medical Association. 226 (11): 1855-1863; Published: June 1, 2005).
Regarding claims 49-51, Fleck et al. teaches treating dogs primed with IL-31 to induce pruritus with subcutaneous lokivetmab, a monoclonal anti-IL-31 antibody approved for the treatment of atopic dermatitis; see Abstract. Regarding claims 49 and 53, Fleck et al. teaches quantifying pruritic behavior 1 day, 7 days, 14 days, 28 days, 42 days, and 52 days following lokivetmab treatment with the cumulative number of “yes” determinations to pruritic behavior per minute is each individual’s pruritus score; see page 682. Regarding claim 52, pruritic behavior includes scratching, licking, scooting; see page 682 right column.
Fleck et al. does not teach comparing to a baseline measure of pruritic behavior nor a relative reduction of 75%.
Regarding claim 49, Steffan et al. teaches evaluating the efficacy of cyclosporine in dogs with atopic dermatitis; see Abstract. Regarding step (b) of claim 49, pruritic behavior in the dogs was evaluated prior to the initiation of treatment and at the end of a 4-week treatment period; see page 1856 right column. Owners were asked to rate the severity of pruritic on a scale of 1 to 5 based on the quantity of pruritic behavior.
It would have been obvious to one of ordinary skill in the art and one would have a reasonable expectation of success to compare baseline, pre-treatment pruritic behavior to measured, post-treatment pruritic behavior as taught by Steffan et al. because, in contrast to Fleck et al. which induced pruritus by IL-31 injection, the severity of atopic dermatitis and displayed pruritic behavior differs from individual to individual and a pre- and post-treatment comparison may have less variability than treatment group comparisons of individuals with natural disease. Further, it would have been obvious to identify a candidate anti-IL-31 antibody as having antipruritic activity when the measured pruritic behavior is reduced relative to the baseline because both Fleck et al. and Steffan et al. teach reduced pruritic behavior is indicative of antipruritic activity of a potential therapeutic agent. Step d) “selecting […] for further development” is indefinite. However, it would have been obvious to one of ordinary skill in the art to further develop an anti-IL-31 antibody with demonstrated anti-pruritic activity in order to market it as a therapeutic for pruritic conditions.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Claims 63 and 64 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Fleck et al. (Veterinary Dermatology. 32: 681-684; Published Online: April 8, 2021) in view of Steffan et al. (Journal of American Veterinary Medical Association. 226 (11): 1855-1863; Published: June 1, 2005), Gotoh et al. (European Journal of Pharmacology. 650 (2011): 215-219; Published Online: October 15, 2010), and Grimstad et al. (Experimental Dermatology. 18: 35-43; Published: October 24, 2008)
Regarding claim 63, Fleck et al. teaches treating dogs primed with IL-31 to induce pruritus with subcutaneous lokivetmab, a monoclonal anti-IL-31 antibody approved for the treatment of atopic dermatitis; see Abstract. Regarding claims 63 and 64, Fleck et al. teaches quantifying pruritic behavior 1 day, 7 days, 14 days, 28 days, 42 days, and 52 days following lokivetmab treatment with the cumulative number of “yes” determinations to pruritic behavior per minute is each individual’s pruritus score; see page 682. Regarding claim 63, pruritic behavior includes scratching, licking, scooting; see page 682 right column.
Fleck et al. does not teach comparing to a baseline measure of pruritic behavior nor a relative reduction of 75%.
Regarding claim 63, Steffan et al. teaches evaluating the efficacy of cyclosporine in dogs with atopic dermatitis; see Abstract. Regarding step (b) of claim 63, pruritic behavior in the dogs was evaluated prior to the initiation of treatment and at the end of a 4-week treatment period; see page 1856 right column. Owners were asked to rate the severity of pruritic on a scale of 1 to 5 based on the quantity of pruritic behavior.
It would have been obvious to one of ordinary skill in the art and one would have a reasonable expectation of success to compare baseline, pre-treatment pruritic behavior to measured, post-treatment pruritic behavior as taught by Steffan et al. because, in contrast to Fleck et al. which induced pruritus by IL-31 injection, the severity of atopic dermatitis and displayed pruritic behavior differs from individual to individual and a pre- and post-treatment comparison may have less variability than treatment group comparisons of individuals with natural disease. Further, it would have been obvious to identify a candidate anti-IL-31 antibody as antipruritic activity when the measure pruritic behavior is reduced relative to the baseline because both Fleck et al. and Steffan et al. teach reduced pruritic behavior is indicative of antipruritic activity of a potential therapeutic agent.
Regarding claim 63 and the 75% relative reduction in pruritic activity, it would have been obvious to optimize the threshold for identifying in vivo efficacy to arrive at least 75% relative reduction as a cutoff determining a candidate anti-IL-31 antibody has antipruritic activity or in vivo efficacy. Indeed, the threshold would be expected to change depending on the tested population (e.g. simply having pruritus versus having atopic dermatitis), the therapeutic doses tested, and the timing of pre- and post-treatment evaluations. Gotoh et al. teaches that a statistically significant reduction in pruritic activity was achieved following treatment when biting was reduced by approximately 75% compared to control; see Figure 2. Further, Gotoh et al. demonstrates that not all doses of the therapeutic resulted in statistically significant reduction in pruritic behavior. Moreover, Grimstad et al. demonstrates that the time of the post-treatment evaluation would influence the amount of pruritic behavior observed; see Figure 3. Thus, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success identifying a candidate anti-IL-31 antibody as having antipruritic activity or in vivo efficacy based on an optimized threshold reduction of pruritic behavior. The step of “advancing […] for continued development is indefinite. However, it would have been obvious to one of ordinary skill in the art to further develop an anti-IL-31 antibody with demonstrated anti-pruritic activity in order to market it as a therapeutic for pruritic conditions.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Claims 39-44, 47, 49-59, 61, and 65 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Steffan et al. (Journal of American Veterinary Medical Association. 226 (11): 1855-1863; Published: June 1, 2005), Grimstad et al. (Experimental Dermatology. 18: 35-43; Published: October 24, 2008), Siadak et al. (US 2010/0008909 A1: Published: January 14, 2010), Mizuno et al. (Veterinary Immunology and Immunopathology. 131 (1-2): 140-143; Published: September 15, 2009), and Wonderling et al. (US 2002/0052030 A1; Published: May 2, 2002).
Regarding claims 39, 49, 54, and 56, Steffan et al. teaches evaluating the efficacy of cyclosporine in dogs with atopic dermatitis; see Abstract. Regarding step (b) of claims 39, 49, and 54, pruritic behavior in the dogs was evaluated prior to the initiation of treatment and at the end of a 4-week treatment period; see page 1856 right column. Owners were asked to rate the severity of pruritic on a scale of 1 to 5 based on the quantity of pruritic behavior. Regarding claims 42, 43, 52, 58, and 59 , the pruritic behavior includes scratching, licking, biting/chewing, or body rubbing. Further, regarding claim 42, Tables 1 and 2 of Steffan et al. include baseline pruritic scores indicating that at least one dog in the method demonstrated baseline pruritic behavior.
Steffan et al. teaches using a scoring system based on the estimated quantity of pruritic behavior displayed, but does not teach measuring the number of times a pruritic behavior is displayed.
Regarding quantitatively measuring pruritic behavior in claims 39 and 54 and measuring the number of times a pruritic behavior is displayed in claims 44, 53, and 60, Grimstad et al. measures the number of scratching counts in mice following IL-31 treatment; see Figure 3. Regarding measuring pruritic behavior within one week of administering the anti-IL-31 antibody in claim 49 and 54, Grimstad et al. administered the anti-IL-31 antibody every 5 days and evaluates scratching behavior every week; see “Intervention” and “Clinical Assessment”. Regarding claim 65, Grimstad et al. demonstrates efficacy of reducing pruritic behavior (ie. scratching) with an anti-IL-31 antibody compared album and untreated controls through 42 days or 6 weeks; see Figure 3.
Regarding claims 39, 40, 49, 50, 54, 55, and 56, Siadak et al. teaches a monoclonal anti-IL-31 antibody that neutralizes the activity of human IL-31 and can be used to treat atopic dermatitis; see Abstract and Example 7. Siadak et al. teaches that IL-31 antagonists are used to improve clinical outcome of dermatitis and pruritic diseases including atopic dermatitis, prurigo nodularis, and eczema by inhibition, reduction, prevention or blocking the inflammation and/or scratching associated with disease; see paragraph 0137. Regarding claims 41, 51, and 57, Siadak et al. teaches that the anti-IL-31 antibody can be administered subcutaneously or intravenously; see paragraph 0208.
Siadak et al. does not teach administering an anti-IL-31 antibody which binds canine IL-31.
Mizuno et al. teaches the sequence of canine IL-31; see Figure 1. Mizuno et al. teaches that dogs express IL-31 mRNA; see Figure 2. Mizuno et al. teaches that humans and mice with atopic dermatitis overexpress IL-31 mRNA in their skin; see page 142.
Mizuno et al. does not teach a canine anti-IL-31 antibody.
Wonderling et al. teaches methods of producing antibodies against a canine cytokine; see paragraphs 0088 and 0096. Wonderling et al. teaches producing monoclonal antibodies; see paragraphs 0049 and 0087.
Given that Steffan et al. and Mizuno et al. teach the dogs develop atopic dermatitis, cyclosporine treatment is not known to be safe long-term and is associated with impaired renal function, and IL-31 is overexpressed in the skin of subjects with atopic dermatitis, it would have been obvious to one of ordinary skill in the art to develop an antibody to antagonize the action of canine IL-31. Moreover, given that Siadak et al. teaches using an antibody against human IL-31 to treat pruritic diseases and reducing the symptoms of atopic dermatitis, one of ordinary skill in the art would have had a reasonable expectation of success to treat atopic dermatitis in dogs with an anti-IL-31 antibody. Step d) “selecting […] for further development” in claim 49 is indefinite. However, it would have been obvious to one of ordinary skill in the art to further develop an anti-IL-31 antibody with demonstrated anti-pruritic activity in order to market it as a therapeutic for pruritic conditions.
Because Mizuno et al. teaches the sequence of canine IL-31 and Wonderling et al. teaches immunizing mammals to generate antibodies against cytokines, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to use the sequence and method taught by Mizuno et al. and Wonderling et al. to produce an anti-canine IL-31 antibody.
Indeed, the development of a method to assess the antipruritic activity and in vivo efficacy of the produced anti-dog IL-31 antibodies is needed to validate that a candidate anti-IL-31 antibody reduces pruritic symptoms. Steffan et al. teaches a method of evaluating in vivo efficacy or antipruritic activity of an agent comprising measuring pre- and post-treatment pruritic behavior, comparing the pre- and post-treatment levels of pruritic behavior, and identifying the agent administered as having efficacy or antipruritic activity when the pruritic behavior is reduced. The method of Steffan et al. relies on owners rating pruritic behavior based on an estimated quantity of pruritic behavior placing each dog into a categorical scoring index. The method of Steffan et al. could be improved by making the data more empirical and relying less on estimations of behavior and impressions of treatment response by modifying Steffan et al. to observe and measuring the pruritic behaviors similar to Grimstad et al. It would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to combine the methods of Steffan et al. and Grimstad et al. because both references evaluate a therapeutic for the treatment of atopic dermatitis. It would have been obvious to one of ordinary skill in the art that a mouse and dog have different body sizes and using the paw magnet and MicroAct device taught for use with mice in Grimstad et al. to measure the duration of pruritic behavior may not be appropriate for use with all dogs and to modify the method to measure absolute counts of observed pruritic behavior and scores based on measured counts rather than owner estimations. Further, it would have been obvious to one of ordinary skill in the art that candidate anti-IL-31 antibodies which result in reduced post-treatment pruritic behavior compared to baseline pruritic behavior, similar to Steffan et al., demonstrate antipruritic activity and in vivo efficacy in treating pruritic conditions, including atopic dermatitis.
Regarding claims 47 and 61 and baseline pruritic behavior measured immediately prior to administration of the candidate anti-IL-31, Grimstad et al. Figure 3 demonstrates that even in untreated mice the severity or quantity of pruritic behavior in atopic dermatitis waxes and wanes over time. It would have been obvious to one of ordinary skill in the art assess baseline pruritic behavior immediately prior to candidate anti-IL-31 antibody administration in order limit the potential confounding of the natural fluctuation of pruritic behavior in atopic dermatitis.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Claims 46 is rejected under 35 U.S.C. 103 as being unpatentable over Steffan et al. (Journal of American Veterinary Medical Association. 226 (11): 1855-1863; Published: June 1, 2005), Grimstad et al. (Experimental Dermatology. 18: 35-43; Published: October 24, 2008), Siadak et al. (US 2010/0008909 A1: Published: January 14, 2010), Mizuno et al. (Veterinary Immunology and Immunopathology. 131 (1-2): 140-143; Published: September 15, 2009), and Wonderling et al. (US 2002/0052030 A1; Published: May 2, 2002) as applied to claim(s) 39-44, 47, 49-52, 54-59, and 61 above, and further in view of Costa et al. (British Journal of Pharmacology. 154: 1094-1103; Published Online: May 5, 2008).
The teachings of Steffan et al., Grimstad et al., Siadak et al., Mizuno et al., and Wonderling et al. as related to claim(s) 39-44, 47, 49-52, 54-59, and 61, from which these claims depend are given previously in this Office action and are fully incorporated here.
Neither Steffan et al., Grimstad et al., Siadak et al., Mizuno et al., nor Wonderling et al. teach a 1-hour acclimatization time.
Regarding claim 46, Costa et al. teaches an acclimatization period of at least 1 hour prior to observation of pruritic behavior; see page 1095 right column.
While Grimstad et al. teaches an acclimatization period of at least 30 minutes prior to pruritic behavior observation, Costa et al. teaches an acclimatization period of at least 1 hour. Given that Grimstad et al. teaches an acclimatization period of at least 30 minutes (30 minutes or longer) and Costa et al. teaches an acclimatization period of at least 1 hour (1 hour or longer), it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to allow for an acclimatization period of at least 30 minutes, including at least 1 hour, prior to the baseline observation period.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Claims 45, 48, 60, and 62-64 are rejected under 35 U.S.C. 103 as being unpatentable over Steffan et al. (Journal of American Veterinary Medical Association. 226 (11): 1855-1863; Published: June 1, 2005), Grimstad et al. (Experimental Dermatology. 18: 35-43; Published: October 24, 2008), Siadak et al. (US 2010/0008909 A1: Published: January 14, 2010), Mizuno et al. (Veterinary Immunology and Immunopathology. 131 (1-2): 140-143; Published: September 15, 2009), and Wonderling et al. (US 2002/0052030 A1; Published: May 2, 2002) as applied to claim(s) 39-44, 47, 49-52, 54-59, and 61 above, and further in view of Gotoh et al. (European Journal of Pharmacology. 650 (2011): 215-219; Published Online: October 15, 2010).
The teachings of Steffan et al., Grimstad et al., Siadak et al., Mizuno et al., and Wonderling et al. as related to claim(s) 39-44, 47, 49-52, 54-59, and 61, from which these claims depend are given previously in this Office action and are fully incorporated here.
Neither Steffan et al., Grimstad et al., Siadak et al., Mizuno et al., nor Wonderling et al. teach a video surveillance or at least 75% reduction in pruritic behavior.
Regarding claims 45 and 60, Gotoh et al. teaches videotaping the pruritic behavior following treating while personnel are outside of the observation room; see page 216.
It would have been obvious to one or ordinary skill in the art to video tape the behavioral observation period with personnel outside of the observation. One would have been motivated to modify the method taught by Steffan et al., Grimstad et al., Siadak et al., Mizuno et al., and Wonderling et al. to include remote video observation because removing personnel from the observation room may reduce stress, a confound variable. Gotoh et al. notes that because the treatment step was recorded on the videotape, experiments were conducted in a single blind manner. One would have been motivated to modify the method to conduct live video monitoring as, unlike Gotoh et al., live video monitoring of an observation area would enable double blinded behavior assessment.
Regarding claims 48 and 62-64 and the 75% relative reduction in pruritic activity, it would have been obvious to optimize a threshold for identifying antipruritic activity or in vivo efficacy to arrive at least 75% relative reduction as a cutoff determining a candidate anti-IL-31 antibody has antipruritic activity or in vivo efficacy. Indeed, the threshold would be expected to change depending on the tested population (e.g. simply having pruritus versus having atopic dermatitis), the therapeutic doses tested, and the timing of pre- and post-treatment evaluations. Gotoh et al. teaches that a statistically significant reduction in pruritic activity was achieved following treatment when biting was reduced by approximately 75% compared to control; see Figure 2. Further, Gotoh et al. demonstrates that not all doses of the therapeutic resulted in statistically significant reduction in pruritic behavior. Moreover, Grimstad et al. demonstrates that the time of the post-treatment evaluation would influence the amount of pruritic behavior observed; see Figure 3. Thus, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success identifying a candidate anti-IL-31 antibody as having antipruritic activity or in vivo efficacy based on an optimized threshold reduction of pruritic behavior. The step of “advancing […] for continued development in claim 63 is indefinite. However, it would have been obvious to one of ordinary skill in the art to further develop an anti-IL-31 antibody with demonstrated anti-pruritic activity in order to market it as a therapeutic for pruritic conditions.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 39, 40, 42-45, 47, 49, 50, 52-56, and 58-61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8-19 of U.S. Patent No. 10,526,405 B2 in view of Steffan et al. (Journal of American Veterinary Medical Association. 226 (11): 1855-1863; Published: June 1, 2005) and Grimstad et al. (Experimental Dermatology. 18: 35-43; Published: October 24, 2008).
Regarding evaluating antipruritic activity or in vivo efficacy in instant claims 39, 49 and 54, issued claim 1 teaches evaluating antipruritic activity of an IL-31 inhibitor in an in vivo study in dogs. Regarding instant claims 40, 42, 44, 50, 53, 55, and 58, issued claims 1 and 14 teach first administering IL-31 to induce pruritus, quantifying pruritic behavior, administering an IL-31 inhibitor, including a monoclonal anti-IL-31 antibody, and assessing effectiveness of the IL-31 based on reduction of pruritic behavior following administration of the IL-31 inhibitor. Regarding the scoring system in instant claim 49, issued claims 9-12 teach a cumulative pruritic score index. Regarding instant claims 43, 52, and 59, issued claim teaches pruritic behaviors of licking, chewing, scratching, head-shaking, and scooting. Regarding instant claims 45 and 60, issued claim 9 teaches using real-time video surveillance to measure behavior.
The issued claims do not teach treating dogs which have a naturally occurring pruritic condition like atopic dermatitis.
Regarding instant claims 39, 49, 54, and 56, Steffan et al. teaches evaluating the efficacy of cyclosporine in dogs with atopic dermatitis; see Abstract. Regarding step (b) of instant claims 39, 49, and 54, pruritic behavior in the dogs was evaluated prior to the initiation of treatment and at the end of a 4-week treatment period; see page 1856 right column. Owners were asked to rate the severity of pruritic on a scale of 1 to 5 based on the quantity of pruritic behavior. Regarding instant claims 42, 43, 52, 58, and 59, the pruritic behavior includes scratching, licking, biting/chewing, or body rubbing. Further, regarding claim 42, Tables 1 and 2 of Steffan et al. include baseline pruritic scores indicating that at least one dog in the method demonstrated baseline pruritic behavior.
The issued claims and Steffan et al. teaches using a scoring system based on the estimated quantity of pruritic behavior displayed, but neither teach measuring the number of times a pruritic behavior is displayed.
Regarding quantitatively measuring pruritic behavior in instant claims 39 and 54 and measuring the number of times a pruritic behavior is displayed in instant claims 44, 53, and 60, Grimstad et al. measures the number of scratching counts in mice following IL-31 treatment; see Figure 3. Regarding measuring pruritic behavior within one week of administering the anti-IL-31 antibody in instant claim 49 and 54, Grimstad et al. administered the anti-IL-31 antibody every 5 days and evaluates scratching behavior every week; see “Intervention” and “Clinical Assessment”.
Both the issued claims and Steffan et al. teach methods of evaluating in vivo efficacy or antipruritic activity of an agent comprising measuring pre- and post-treatment pruritic behavior, comparing the pre- and post-treatment levels of pruritic behavior, and identifying the agent administered as having efficacy or antipruritic activity when the pruritic behavior is reduced. While the issued claims do not explicitly recite counting the number of behaviors, issued claim 1 encompasses measuring the number of behaviors. The method of Steffan et al. relies on owners rating pruritic behavior based on an estimated quantity of pruritic behavior placing each dog into a categorical scoring index and could be improved by making the data more empirical and relying less on estimations of behavior and impressions of treatment response by modifying Steffan et al. to observe and measuring the pruritic behaviors similar to Grimstad et al. - counting pruritic behaviors. It would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to combine the methods of the issued claims, Steffan et al., and Grimstad et al. because all references evaluate a therapeutic for the treatment of atopic dermatitis or a pruritic condition. It would have been obvious to one of ordinary skill in the art that a mouse and dog have different body sizes and using the paw magnet and MicroAct device taught for use with mice in Grimstad et al. to measure the duration of pruritic behavior may not be appropriate for use with all dogs and absolute counts of observed pruritic behavior would be an obvious alternative. Further, it would have been obvious to one of ordinary skill in the art that candidate anti-IL-31 antibodies which result in reduced post-treatment pruritic behavior compared to baseline pruritic behavior, similar to Steffan et al., demonstrate antipruritic activity and in vivo efficacy in treating pruritic conditions, including atopic dermatitis. Step d) “selecting […] for further development” in claim 49 is indefinite. However, it would have been obvious to one of ordinary skill in the art to further develop an anti-IL-31 antibody with demonstrated anti-pruritic activity in order to market it as a therapeutic for pruritic conditions.
Regarding instant claims 47 and 61 and baseline pruritic behavior measured immediately prior to administration of the candidate anti-IL-31, Grimstad et al. Figure 3 demonstrates that even in untreated mice the severity or quantity of pruritic behavior in atopic dermatitis waxes and wanes over time. It would have been obvious to one of ordinary skill in the art assess baseline pruritic behavior immediately prior to candidate anti-IL-31 antibody administration in order limit the potential confounding of the natural fluctuation of pruritic behavior in atopic dermatitis.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Claims 41, 51, and 57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8-19 of U.S. Patent No. 10,526,405 B2 in view of Steffan et al. (Journal of American Veterinary Medical Association. 226 (11): 1855-1863; Published: June 1, 2005) and Grimstad et al. (Experimental Dermatology. 18: 35-43; Published: October 24, 2008) as applied to claim(s) 39, 40, 42-45, 47, 49, 50, 52-56, and 58-61 above, and further in view of Siadak et al. (US 2010/0008909 A1: Published: January 14, 2010).
The teachings of the issued claims in view of Steffan et al. and Grimstad et al. as related to claim(s) 39, 40, 42-45, 47, 49, 50, 52-56, and 58-61, from which these claims depend are given previously in this Office action and are fully incorporated here.
Neither the issued claims, Steffan et al., nor Grimstad et al. teach administering an anti-IL-31 antibody subcutaneously or intravenously.
Siadak et al. teaches a monoclonal anti-IL-31 antibody that neutralizes the activity of human IL-31 and can be used to treat atopic dermatitis; see Abstract and Example 7. Siadak et al. teaches that IL-31 antagonists are used to improve clinical outcome of dermatitis and pruritic diseases including atopic dermatitis, prurigo nodularis, and eczema by inhibition, reduction, prevention or blocking the inflammation and/or scratching associated with disease; see paragraph 0137. Regarding claims 41, 51, and 57, Siadak et al. teaches that the anti-IL-31 antibody can be administered subcutaneously or intravenously; see paragraph 0208.
Given the Siadak et al. teaches the anti-IL-31 antibodies can be administered subcutaneously or intravenously, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to administer the candidate anti-IL-31 antibody in the issued claims subcutaneously or intravenously. Moreover, one would be motivated to make this modification because the issued claims teach parenteral administration, which encompass subcutaneous or intravenous routes; see issued claim 19.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Claim 46 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8-19 of U.S. Patent No. 10,526,405 B2 in view of Steffan et al. (Journal of American Veterinary Medical Association. 226 (11): 1855-1863; Published: June 1, 2005) and Grimstad et al. (Experimental Dermatology. 18: 35-43; Published: October 24, 2008) as applied to claim(s) 39, 40, 42-45, 47, 49, 50, 52-56, and 58-61 above, and further in view of Costa et al. (British Journal of Pharmacology. 154: 1094-1103; Published Online: May 5, 2008).
The teachings of the issued claims in view of Steffan et al. and Grimstad et al. as related to claim(s) 39, 40, 42-45, 47, 49, 50, 52-56, and 58-61, from which these claims depend are given previously in this Office action and are fully incorporated here.
Neither the issued claims, Steffan et al., nor Grimstad et al. teach an acclimation period of at least 1 hour.
Regarding claim 46, Costa et al. teaches an acclimatization period of at least 1 hour prior to observation of pruritic behavior; see page 1095 right column.
While Grimstad et al. teaches an acclimatization period of at least 30 minutes prior to pruritic behavior observation, Costa et al. teaches an acclimatization period of at least 1 hour. Given that Grimstad et al. teaches an acclimatization period of at least 30 minutes (30 minutes or longer) and Costa et al. teaches an acclimatization period of at least 1 hour (1 hour or longer), it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to allow for an acclimatization period of at least 30 minutes, including at least 1 hour, prior to the baseline observation period. One would have been motivated to add this acclimatization period to the method of the issued claims in order to reduce stress as a confounding variable.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Claims 48 and 62-64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8-19 of U.S. Patent No. 10,526,405 B2 in view of Steffan et al. (Journal of American Veterinary Medical Association. 226 (11): 1855-1863; Published: June 1, 2005) and Grimstad et al. (Experimental Dermatology. 18: 35-43; Published: October 24, 2008) as applied to claim(s) 39, 40, 42-45, 47, 49, 50, 52-56, and 58-61 above, and further in view of Gotoh et al. (European Journal of Pharmacology. 650 (2011): 215-219; Published Online: October 15, 2010).
The teachings of the issued claims in view of Steffan et al. and Grimstad et al. as related to claim(s) 39, 40, 42-45, 47, 49, 50, 52-56, and 58-61, from which these claims depend are given previously in this Office action and are fully incorporated here.
Neither the issued claims, Steffan et al., nor Grimstad et al. teach a threshold of 75% relative reduction.
Similar to the method of the issued claims, Gotoh et al. teaches a method of administering a pruritic agent to create a model with which to evaluate the antipruritic activity of agents; see Abstract.
Regarding instant claims 48 and 62-64 and the 75% relative reduction in pruritic activity, it would have been obvious to optimize a threshold for identifying antipruritic activity or in vivo efficacy to arrive at least 75% relative reduction as a cutoff determining a candidate anti-IL-31 antibody has antipruritic activity or in vivo efficacy. Indeed, the threshold would be expected to change depending on the tested population (e.g. simply having pruritus versus having atopic dermatitis), the therapeutic doses tested, and the timing of pre- and post-treatment evaluations. Gotoh et al. teaches that a statistically significant reduction in pruritic activity was achieved following treatment when biting behavior was reduced by approximately 75% compared to control; see Figure 2. Further, Gotoh et al. demonstrates that not all doses of the therapeutic resulted in statistically significant reduction in pruritic behavior. Moreover, Grimstad et al. demonstrates that the time of the post-treatment evaluation would influence the amount of pruritic behavior observed; see Figure 3. Thus, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success identifying a candidate anti-IL-31 antibody as having antipruritic activity or in vivo efficacy based on an optimized threshold reduction of pruritic behavior. The step of “advancing […] for continued development in claim 63 is indefinite. However, it would have been obvious to one of ordinary skill in the art to further develop an anti-IL-31 antibody with demonstrated anti-pruritic activity in order to market it as a therapeutic for pruritic conditions.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Claims 39, 40, 42-44, 54-56, and 58-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 11, 13-15, 18-25, 27, 31, and 34-38 of copending Application No. 19/202,626 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 39, 42-44, 54, and 58-60, copending claims 1-8, 13-15, 18, 19, 21-25, and 34-38 teach a method of assessing antipruritic activity of a candidate anti-IL-31 antibody comprising measuring pruritic behavior displayed by a dog, assigning a score based on the intensity of the pruritic behavior, administering a candidate anti-IL-31 antibody to the dog, measuring post-treatment pruritic behavior, and identifying the antibody as having antipruritic activity when there is a reduction in the post-treatment score compared to the pre-treatment score. Note that intensity is not defined in the copending specification and is interpreted to mean the quantity or number of times a pruritic behavior is displayed.
Regarding instant claims 40 and 55, copending claims 20 and 36 teach that a monoclonal anti-IL-31 antibody is administered.
Regarding instant claims 56, copending claim 31 teaches the dog has atopic dermatitis.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 41 and 57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 11, 13-15, 18-25, 27, 31, and 34-38 of copending Application No. 19/202,626, as applied to claim(s) 39, 40, 42-44, 54-56, and 58-60 above, and in view of Siadak et al. (US 2010/0008909 A1: Published: January 14, 2010).
The teachings of copending Application No. 19/202,626 as related to claim(s) 39, 40, 42-44, 54-56, and 58-60, from which these claims depend are given previously in this Office action and are fully incorporated here.
Copending Application No. 19/202,626 does not teach administering the antibody subcutaneously or intravenously.
Regarding claims 41 and 57, Siadak et al. teaches that the anti-IL-31 antibody can be administered subcutaneously or intravenously; see paragraph 0208.
Given that Siadak et al. teaches using an antibody against human IL-31 to treat pruritic diseases and reducing the symptoms of atopic dermatitis, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to treat atopic dermatitis in dogs with a candidate anti-IL-31 antibody administered subcutaneously or intravenously.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 46 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 11, 13-15, 18-25, 27, 31, and 34-38 of copending Application No. 19/202,626, as applied to claim(s) 39, 40, 42-44, 54-56, and 58-60 above, and in view of Costa et al. (British Journal of Pharmacology. 154: 1094-1103; Published Online: May 5, 2008) and Grimstad et al. (Experimental Dermatology. 18: 35-43; Published: October 24, 2008).
The teachings of copending Application No. 19/202,626 as related to claim(s) 39, 40, 42-44, 54-56, and 58-60, from which these claims depend are given previously in this Office action and are fully incorporated here.
Copending Application No. 19/202,626 does not teach an acclimatization period of at least 1 hour prior to observation of pruritic behavior
Regarding instant claim 46, Costa et al. teaches an acclimatization period of at least 1 hour prior to observation of pruritic behavior; see page 1095 right column.
While Grimstad et al., which similarly teaches a mouse model of assessing anti-13 antibody based on pruritic behavior, teaches an acclimatization period of at least 30 minutes prior to pruritic behavior observation, Costa et al. teaches an acclimatization period of at least 1 hour. Given that Grimstad et al. teaches an acclimatization period of at least 30 minutes (30 minutes or longer) and Costa et al. teaches an acclimatization period of at least 1 hour (1 hour or longer), it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to allow for an acclimatization period of at least 30 minutes, including at least 1 hour, prior to the baseline observation period.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 45, 47-53, and 60-64 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 11, 13-15, 18-25, 27, 31, and 34-38 of copending Application No. 19/202,626, as applied to claim(s) 39, 40, 42-44, 54-56, and 58-60 above, and in view of Grimstad et al. (Experimental Dermatology. 18: 35-43; Published: October 24, 2008), Siadak et al. (US 2010/0008909 A1: Published: January 14, 2010), and Gotoh et al. (European Journal of Pharmacology. 650 (2011): 215-219; Published Online: October 15, 2010).
The teachings of copending Application No. 19/202,626 as related to claim(s) 39, 40, 42-44, 54-56, and 58-60, from which these claims depend are given previously in this Office action and are fully incorporated here.
Copending Application No. 19/202,626 does not teach assessing pruritic behavior within one week of administration of the anti-IL-31 antibody nor a baseline pruritic behavior assessment conducted immediately before administration of the anti-IL-31 antibody.
Regarding quantifying pruritic behavior within one week as in instant claims 49 and 63, from which instant claims 50-53 and 64 depend, Grimstad et al. teaches quantifying scratching behavior at Day 7 following anti-IL-31 antibody treatment.
Neither the copending claims nor Grimstad et al. teach observing behavior via video surveillance.
Regarding claims 45 and 60, Gotoh et al. teaches videotaping the pruritic behavior following treating while personnel are outside of the observation room; see page 216.
Neither the copending claims, Grimstad et al. nor Gotoh et al. teach administering the anti-IL-31 anitbody subcutaneously or intravenously.
Regarding claim 51, Siadak et al. teaches that the anti-IL-31 antibody can be administered subcutaneously or intravenously; see paragraph 0208.
Given that the copending pending claims do not specify a post-treatment observation window and the Grimstad et al. teaches a similar method of measuring pruritic behavior following anti-IL-31 antibody administration, it would have been obvious and one would have had a reasonable expectation of success to combine the method the copending claims with Grimstad et al. and measure behavior within one week post-treatment.
Regarding instant claims 47 and 61 and baseline pruritic behavior measured immediately prior to administration of the anti-IL-31, Grimstad et al. Figure 3 demonstrates that even in untreated mice the severity or quantity of pruritic behavior in atopic dermatitis waxes and wanes over time. It would have been obvious to one of ordinary skill in the art assess baseline pruritic behavior immediately prior to anti-IL-31 antibody administration in order limit the potential confounding of the natural fluctuation of pruritic behavior in atopic dermatitis.
It would have been obvious to one or ordinary skill in the art to video tape the behavioral observation period with personnel outside of the observation. One would have been motivated to modify the method taught by the copending claims to include remote video observation because removing personnel from the observation room may reduce stress, a confound variable. Gotoh et al. notes that because the treatment step was recorded on the videotape, experiments were conducted in a single blind manner. One would have been motivated to modify the method to conduct live video monitoring as, unlike the single blind evaluation of Gotoh et al., live video monitoring would enable double blinded behavior assessment.
Regarding claims 48 and 62-64 and the 75% relative reduction in pruritic activity, it would have been obvious to optimize the predefined threshold taught by the copending claims to arrive at least 75% relative reduction as a cutoff determining a candidate anti-IL-31 antibody has antipruritic activity or in vivo efficacy. Indeed, the threshold would be expected to change depending on the tested population (e.g. simply having pruritus versus having atopic dermatitis), the therapeutic doses tested, and the timing of pre- and post-treatment evaluations. Gotoh et al. teaches that a statistically significant reduction in pruritic activity was achieved following treatment when biting was reduced by approximately 75% compared to control; see Figure 2. Further, Gotoh et al. demonstrates that not all doses of the therapeutic resulted in statistically significant reduction in pruritic behavior. Moreover, Grimstad et al. demonstrates that the time of the post-treatment evaluation would influence the amount of pruritic behavior observed; see Figure 3. Thus, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success identifying a candidate anti-IL-31 antibody as having antipruritic activity or in vivo efficacy based on an optimized threshold reduction of pruritic behavior.
Finally, given that Siadak et al. teaches using an antibody against human IL-31 to treat pruritic diseases and reducing the symptoms of atopic dermatitis, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to treat atopic dermatitis in dogs with a candidate anti-IL-31 antibody administered subcutaneously or intravenously. The steps of “selecting […] for further development” and “advancing […] for continued development in claims 49 and 63 are indefinite. However, it would have been obvious to one of ordinary skill in the art to further develop an anti-IL-31 antibody with demonstrated anti-pruritic activity in order to market it as a therapeutic for pruritic conditions.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant’s amendments filed July 14, 2026 are acknowledged. Any rejection not repeated above is resolved by amendment.
Regarding priority, Applicant argues that because a chimeric anti-IL-31 antibody was tested for anti-pruritic activity in a dog pruritus model and demonstrated reduced pruritic scored in treated dogs, was caninized, then evaluated again for anti-pruritic activity in another dog model that the candidate anti-IL-31 antibody was selected or advanced for further development.
First, there is no limiting definition in the Specification which restricts candidate anti-IL-31 antibody to only the chimeric anti-IL-31 antibody. Candidate anti-IL-31 antibody also encompasses the caninized anti-IL-31 antibody.
Second, and more importantly, “further development as an anti-pruritic therapeutic for the treatment of atopic dermatitis” or “continued development for the treatment of atopic dermatitis” could encompass any number of activities, such as: optimizing excipients, filing regulatory paperwork, conducting further trials, or designing commercial marketing materials. Applicant has only disclosed one activity as potential development (i.e. canonizing an antibody), which is not commensurate with the scope of “further[ing] development as an anti-pruritic therapeutic for the treatment of atopic dermatitis”.
Regarding the rejections of claims 49-53 and 63-64 under 35 U.S.C. 112(b), Applicant argues that the addition of identifying the candidate antibody resolves the issue with the selecting for further or advancing for continued development.
Because identifying and, selecting or advancing, are two subordinate clauses separated by the word “and” both actions must be performed. It is still unclear what action must be completed to meet “selecting […] for further development” or “advancing the candidate […] for continued development”. The steps of “selecting” or “advancing” appear to be mental steps. If the steps of “selecting” or “advancing” were to require further action, it is unclear what activities does Applicant consider to meet “selecting” for further development or “advancing” for continued development?
Regarding the rejection of claims 54-62 under 35 U.S.C. 112(b), Applicant argues that the claim does not require a single measurement to simultaneously satisfy both the “within one week” and “one to two weeks” timeframes. Further, Applicant asserts that “the claim establishes that an initial measurement is taken within own week, and the efficacy determination is based on whether the reduction persists for at least one to two weeks”. Examiner disagrees. Steps (c) and (d) recite “the measured pruritic activity” and this limitation has antecedent basis in step (b) “quantitatively measuring at least one pruritic behavior in the dog within one week of administration of the anti-IL-31 antibody”. The claim only requires one measurement within one week. It is unclear how “the measured pruritic activity” assessed within one week is used to establish that the pruritic behavior is reduced for one to two weeks. If a measurement between one to two weeks or at two weeks is not required to the claim – which it is not required because it is not recited – then can one simply declare the pruritic activity reduced for at least one to two weeks to meet the limitations of step (d)? Applicant argues that more than one measurement must be taken to complete steps (b) and (d), but the claim only require one measurement within one week.
On page 13, regarding the rejection of claims 49-53 under 35 U.S.C. 103(a) over Fleck et al. in view of Steffan et al., Applicant’s arguments relate the amended recitation of a “candidate anti-IL-31 antibody” and are addressed in the updated rejection as necessitated by amendment.
On page 14, regarding the rejection of claims 63 and 64 under 35 U.S.C. 103(a) over Fleck et al. in view of Steffan et al., Gotoh et al., and Grimstad et al., Applicant argues that the references do not teach “advancing” or “excluding” a candidate for development based on whether or not it reduces pruritic behavior by 75%. The clause related to advancing or excluding were rejected as indefinite and remain rejected as indefinite. As indicated in the 112b rejection, for the purpose of compact prosecution, step (d) is interpreted as requiring identifying a candidate as having in vivo efficacy in the treatment of atopic dermatitis when pruritic behavior score is reduced by at least 75% relative to the baseline – a mental step. Regarding the 75% threshold, Applicant asserts that the “assertion that optimizing a threshold to 75% would have been obvious is conclusory and unsupported by evidence.” Examiner disagrees. Applicant’s assertion overlooks the analysis of the findings presented in Gotoh et al. and Grimstad et al. as discussed in the rationale. Further, on pages 14-15, Applicant argues that the 75% threshold “reflects a deliberate and non-arbitrary design choice that materially impacts the development workflow.” Applicant continues “[i]n example 9, the canine IL-31-induced pruritic model showed that post-IL-31 challenge pruritic scores decreased by at least 85% in overall pruritic reactivity after treatment with caninized 34D03”. Applicant has not provided any evidence as to the criticality of the 75% threshold nor any explanation for the discrepancy between the showing of 85% reduction, but the recitation of a 75% threshold.
On pages 15-16, regarding the rejection of claims 39-44, 47, 49-59, and 61 under 35 U.S.C. 103(a) as being unpatentable over Steffan et al., Grimstad et al., Siadak et al., Mizuno et al., and Wonderling et al., Applicant alleges that the Office used improper hindsight and the Office Actions does not identify any disclosure in the cited references that would have led a person of ordinary skill in the art to modify or combine the references to identify, select, or evaluate an anti-IL-31 antibody candidates in dogs by measuring pruritic behavior an comparing to a baseline measurements. Examiner disagrees. MPEP 2145 X.A. states "[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." Moreover, “there is no requirement that an ‘express, written motivation to combine must appear in prior art references before a finding of obviousness.’”; see MPEP 2145 X.A. The obviousness rejection does not include knowledge which was not within the level of ordinary skill in the art at the time the claimed invention was made and provides an explicit rationale for the combination – the rejection is proper.
On page 17, regarding the rejection of claims 39-44, 47, 49-59, and 61 under 35 U.S.C. 103(a) as being unpatentable over Steffan et al., Grimstad et al., Siadak et al., Mizuno et al., and Wonderling et al., Applicant alleges that the references do not teaching identifying an anti-IL-31 antibody as having anti-pruritic activity where measured pruritic activity is reduced relative to baseline nor selecting for further development. Examiner disagrees. The clause selecting for further development remains indefinite. Identifying an anti-IL-31 antibody as having anti-pruritic activity where measured pruritic activity is reduced relative to baseline is addressed in the rationale.
On pages 17-18, regarding the rejection of claims 39-44, 47, 49-59, and 61 under 35 U.S.C. 103(a) as being unpatentable over Steffan et al., Grimstad et al., Siadak et al., Mizuno et al., and Wonderling et al., Applicant asserts that there is no reasonable expectation of success because canine IL-31 may function differently from human or mouse IL-31 “creat[ing] substantial uncertainty about whether anti-IL-31 antibodies would be effective in treating canine atopic dermatitis.” Arguments presented by Applicant cannot take the place of evidence in the record – Applicant has not provided any support for the suggestion that IL-31 in canines would be expected to function differently. On page 18, Applicant argues against Steffan et al. individually stating that cyclosporine evaluated in Steffan et al. has a distinct mechanism from anti-IL-31 antibodies. The rejection has already addressed why one of ordinary skill would be motivated against treating with cyclosporine and towards evaluating the anti-pruritic activity of anti-IL-31 antibodies to treat canine pruritic conditions. Applicant argues that Steffan’s method for evaluating the anti-pruritic activity of cyclosporine cannot be adapted to another potential anti-pruritic agents, but provides no evidence.
On pages 18-19, regarding the rejection of claims 39-44, 47, 49-59, and 61 under 35 U.S.C. 103(a) as being unpatentable over Steffan et al., Grimstad et al., Siadak et al., Mizuno et al., and Wonderling et al., Applicant argues that Grimstad et al. teaches away because teaches that at the end-point (ie. when the mice were sacrificed and biopsied) there was no significant difference in dermatitis between the treatment groups, that there was no weight difference between treatment groups, and that Grimstad et al. teaches “[o]ur results suggest that other factors are needed for the development of dermatitis, and that IL-31 does not play a key role in this pathogenesis in this atopic dermatitis model” [emphasis added].
Examiner disagrees.
First, regarding dermatitis, the findings of Grimstad et al. are presented out of context, with the reference stating just two paragraphs earlier that “[f]or the entire treatment period, the difference in clinically assessed dermatitis between the anti-IL-31 group and non-intervention group was significantly reduced.” In summary, the physical evaluation of live subjects demonstrated significantly reduced clinically assessed dermatitis in the anti-IL-31 antibody treatment group, but when the subjects were euthanized and their skin biopsied, there was no statistical significance between groups. One of ordinary skill in the art would interpret treatment, in line with instant disclosure, to include suppressing clinically assessed symptoms of disease, which Grimstad et al. demonstrated. Additionally, the claims do not require reduced dermatitis presentation by biopsy.
Second, regarding weight, Grimstad et al. states: In humans it is recognized that severe itching negatively affects weight gain (2,29). However, we found no effect of IL-31 antibody treatment of NC⁄ Nga mice on weight development. Here, Grimstad et al. appears to acknowledge that weight loss may not be an analogous symptom in this NC⁄ Nga mouse model. Additionally, all instant claims are to pruritic activity or pruritic behavior – weight loss is not a pruritic behavior or activity evaluated in the instant claims.
Finally, regarding this quote, “[o]ur results suggest that other factors are needed for the development of dermatitis, and that IL-31 does not play a key role in this pathogenesis in this atopic dermatitis model” [emphasis added], Grimstad et al. again appears to acknowledge that these findings may be the result of this specific model. On pages 41-42, Grimstad et al. acknowledges immune response distinctions in NC/Nga mice which may explain why dermatitis at end-point and weight reduction were not significantly different in the anti-IL-31 antibody treatment group.
As humans with atopic dermatitis, NC⁄ Nga mice can develop Th1, Th2, or mixed-type skin lesions. Typically, the first weeks after debut of dermatitis, skin inflammation in NC⁄ Nga is of Th2-type when mice are kept under conventional conditions (10,39). Systemic deficient Th1 response to bacterial stimulation in NC⁄ Nga mice leads to Th2-dominance with excessive production of IgE and atopic-like dermatitis (44), but stimulation with bacterial antigen will over time induce a shift towards Th1 predominance (45–47).
Interestingly, in STAT6-deficient NC⁄ Nga mice, histological features of skin lesions fulfil the criteria for the pathogenesis of AD, although these mice fail to produce IgE and Th2 cytokines (48). Development of atopic dermatitis-like skin lesions in NC⁄ Nga can therefore appear without Th-2 mediated immune response (48). STAT6-deficient NC⁄ Nga mice exhibit scratching behaviour like wild-type NC⁄ Nga mice, with onset prior to clinical manifestation of dermatitis (personal notification from M. Kubo).
We observed an initial effect on scratching behaviour in animals treated with anti IL-31 antibody, but this effect wore off. This suggests a diminishing pruritic role of IL-31 in dermatitis over time. A possible reduction of the acute Th2 dominated phase to a chronic inflammatory state where Th1 responses play a more important role might explain this.
IL-31 is predominantly a cytokine produced under Th2 predominant conditions. As conditions shift towards Th1 preponderance, the role of IL-31 as an important pruritic cytokine may diminish, while other pruritic mediator may concert more important roles. This may explain the time limitation reduction on scratching behaviour for the IL-31 antibody. It is possible that earlier intervention could lead to a different result, both for scratching behaviour and development of dermatitis. However, this would be a change of model, since that would be a prophylactic rather than a treatment study.
However, more importantly, Grimstad et al. concludes that, despite not having a significant impact on weight gain or end-point dermatitis, the “IL-31 antibody reduces scratching behaviour in an atopic dermatitis-like murine model during the onset of clinical skin manifestations. Our findings suggest IL-31 antibody as a new potential therapeutic approach for pruritus in atopic dermatitis and other pruritic diseases”; see Abstract.
On pages 18-19, regarding the rejection of claims 39-44, 47, 49-59, and 61 under 35 U.S.C. 103(a) as being unpatentable over Steffan et al., Grimstad et al., Siadak et al., Mizuno et al., and Wonderling et al., Applicant argues that Mizuno et al. teaches away because the reference teaches that IL-31 mRNA expression was not elevated in dogs with AD, as is in humans or mice models, that the AD induction mechanism may differ in dogs, and that TARC is upregulated in the skin of dogs with AD.
Examiner disagrees.
First, while Mizuno et al. teaches that IL-31 mRNA was not overexpressed in the skin of dogs with AD, the reference acknowledges, on page 143, the limitation of only assessing mRNA expression:
Recently, immunohistochemical staining of human IL-31 in CLA-positive T cells in human skin (Bilsborough et al., 2006) and elevated serum levels of IL-31 in patients with AD (Raap et al., 2008) were reported. Once an antibody to canine IL-31 becomes available, the measurement of serum IL-31 levels or immunohistochemical staining of the skin could be performed to obtain more accurate information reading contribution of IL-31 to the pathogenesis of canine AD [emphasis added].
Additionally, the anti-IL-31 antibody used in the instantly claimed methods does not target IL-31 mRNA, but rather IL-31 protein. Mizuno et al. acknowledges that they have not evaluated IL-31 protein and suggests that those findings may differ from the findings related to IL-31 mRNA.
Second, regarding the statement, “[o]ne possibility is that the mechanism of AD induction in dogs differs”, one of ordinary skill in the art would not interpret treatment as restricted to preventing the induction of a disease.
Finally, if one of ordinary skill in the art might look to TARC as a therapeutic target if presented with Mizuno et al. in isolation, however, not when presented with Steffan et al., Grimstad et al., Siadak et al., Mizuno et al., and Wonderling et al. in combination as discussed in the rejection. Together, these references clearly point to IL-31 as a therapeutic target for AD and pruritic conditions.
On pages 19-20, regarding the rejections of claims 46 under 35 U.S.C. 103(a) as being unpatentable over Steffan et al., Grimstad et al., Siadak et al., Mizuno et al., and Wonderling et al. further in view of Costa et al. and of claims 45, 48, 60, and 62-64 over Steffan et al., Grimstad et al., Siadak et al., Mizuno et al., and Wonderling et al. further in view of Gotoh et al., Applicant argues that Costa et al. and Gotoh et al. teach methods in mice, not dogs, does not cure the deficiencies of Steffan et al., Grimstad et al., Siadak et al., Mizuno et al., and Wonderling et al. Examiner disagrees for the reasons discussed above.
Further, Applicant argues that Examiner has not provide sufficient support for optimization to arrive at the 75% threshold. Examiner disagrees. Rationale for arriving at the 75% threshold is discussed in the rejection.
Lastly, regarding the nonstatutory double patenting rejections over the claims of U.S. Patent No. 10,526,405 and copending Application No. 19/202,626, Applicant states that Applicant is concurrently filing terminal disclaimers. However, no such terminal disclaimers are found on file. The nonstatutory double patenting rejections are maintained.
Conclusion
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/KATHERINE ANN HOLTZMAN/Examiner, Art Unit 1646
/JULIET C SWITZER/Primary Examiner, Art Unit 1682
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