DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The claim listing filed July 10, 2024 is pending.
Claims 1, 4, 5, 9, 10, 12-17, 19-27, 31, 32, and 39-41 are canceled.
Claims 2, 3, 6-8, 11, 18, 28-30, and 33-38 are pending and currently under consideration.
Claim 2 is an independent claim.
Specification
The disclosure is objected to because of the following informalities:
The word “signalling,” which is found at least 40 times throughout the specification should be “signaling.”
Appropriate correction is required.
Claim Objections
Claims 2, 3, 6, 7, 29, 30, 33, and 34 objected to because of the following informalities:
Claims 3, 6-8, 11, 18, 28-30, and 33-38 are all dependent on canceled claim 1. For the purpose of examination, claims 3, 6-8, 11, 18, 28-30, and 33-38 are being read as dependent on claim 2.
The second recitation of the word “treating” should be deleted from line 1 of claim 2.
The word “signalling” should be “signaling” in claims 2, 3, 6, 7, 33, and 34.
In claim 29, the phrase “the group consisting of a topical corticosteroid, a topical calcineurin inhibitor, an anti-histamine, an emollient, or an anti-bacterial therapeutic” should be “the group consisting of a topical corticosteroid, a topical calcineurin inhibitor, an anti-histamine, an emollient, and an anti-bacterial therapeutic” in lines 3-5.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
Indefinite language
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 2, 3, 6-8, 11, 18, 28-30, and 33-38 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.
Claims 2, 3, 6, and 7 recite the phrases "such as an anti-IL4Ra antibody" and/or “(e.g. dupilumab)” which render the claims indefinite because it is unclear whether the limitation(s) following the phrases are part of the claimed invention. See MPEP § 2173.05(d).
The use of the exemplary language, “such as” and “e.g.” in claims 2, 3, 6, and 7 renders the claims indefinite because it is unclear whether the limitations following the phrases “such as” and “e.g.” are part of the claimed invention. Therefore, claims 2, 3, 6, and 7 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
To obviate this part of the rejection, limitations that follows the phrases “such as” and “e.g.” should be claimed in a dependent claim.
For the purposes of applying prior art, the limitations following phrases “such as” and “e.g.” are not being considered.
Claim 2 also recites “the subject who has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signalling” in lines 4 and 5. However, there is no recitation of “a subject who has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signalling” prior to this limitation in the claim. Therefore, “the subject who has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signalling” lacks antecedent basis and renders claim 2 indefinite.
Amending claim 2 to recite “a subject who has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signalling” in lines 4 and 5 would obviate this part of the rejection.
Claims 2 and 28-30 recite “the IL-13 binding protein.” However, there is no recitation of “an IL-13 binding protein” prior to this limitation in the claims. Therefore, the limitation of “the IL-13 binding protein” lacks antecedent basis and renders the claims indefinite.
Amending claim 2 to recite “an IL-13 binding protein” in lines 5 and 6 would obviate this part of the rejection.
Claim 2 also recites “the treatment” in lines 8 and 12. However, there is no recitation of “a treatment” prior to this limitation in claim 2. Therefore, the limitation of “the treatment” lacks antecedent basis and renders the claim indefinite.
Amending claim 2 to replace the phrase “the treatment” with “the method” would obviate this part of the rejection.
Claims 3 and 6 recite “wherein the method comprises the step of selecting a subject” in lines 2-3. It is unclear if the method step recited in claims 3 and 6 is addition to or in place of the step of claim 2. Furthermore, it is also unclear if the step recited in claim 3 happens before or after the step recited in claim 2. Therefore, the claim has been rendered indefinite.
Amending claims 3 and 6 to recite “wherein the method further comprises the step of selecting a subject…prior to the administration of the IL-13 binding protein to the subject subcutaneously” would obviate this part of the rejection.
Claims 37 and 38 recite the phrases “wherein the method achieves >75% improvement of Eczema Area and Severity Index (EASI-75) compared to baseline at week 16” and “wherein the method achieves >75% improvement of Eczema Area and Severity Index (EASI-75) compared to baseline at week 26,” respectively, in lines 2 and 3. However, it is unclear if the baseline or the measurement of EASI-75 is being measured at weeks 16 and 26, respectively. For example, the phrase “baseline at week 16” can be read as the baseline being measured at week 16. However, the claim can also be read as the EASI-75 being measured at week 16. Therefore, the claims have been rendered indefinite.
Amending claims 37 and 38 to “wherein the method achieves, at week 16, a >75% improvement of Eczema Area and Severity Index (EASI-75) compared to baseline” and “wherein the method achieves, at week 26, a >75% improvement of Eczema Area and Severity Index (EASI-75) compared to baseline,” respectively, would obviate this part of the rejection.
Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to that which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to that which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 2, 3, 6-8, 11, 18, 28-30, 33, and 35-38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a method for treating moderate-to-severe or severe atopic dermatitis (AD) in a subject in need thereof, wherein the AD is inadequately controlled by an agent that inhibits IL-13 and IL-4 signaling, such as an anti-IL4Ra antibody (e.g. dupilumab), or wherein the subject who has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signaling, such as an anti-IL4Ra antibody (e.g. dupilumab), wherein the method comprises the step of administering the IL-13 binding protein to the subject subcutaneously, wherein the IL-13 binding protein is tralokinumab and wherein the treatment comprises the steps of: (a) administering a first dose of about 600 mg of the IL-13 binding protein to the subject; and (b) administering one or more secondary dose(s) of about 300 mg of the IL-13 binding protein to the subject, wherein each secondary dose is administered to the subject about 2 weeks or about 4 weeks after the immediately preceding dose, and wherein the treatment is carried out for at least 2 weeks.
The Applicant has disclosed that the agent that inhibits IL-13 and IL-4 signaling may be an antibody or antigen binding fragment thereof, an antibody or antigen binding fragment thereof that binds to IL-4Ra, or dupilumab (e.g. see page 8, lines 17-23). The Applicant has also disclosed that the agent that inhibits IL-13 and IL-4 signaling may be a small molecule inhibitor or an IL-4 mutein (e.g. see page 15, lines 1 and 2).
The Applicant has only disclosed one example to describe the claimed method (e.g. see example 1, spanning pages 39-43). In this example, the Applicant has only disclosed dupilumab as the agent that inhibits IL-13 and IL-4 signaling.
When given the broadest reasonable interpretation in light of specification, the agent of the instant invention is defined broadly to be any agent that inhibits IL-13 and IL-4 signaling.
It is noted that the claims do not recite sufficient structure for the genera of agents that inhibit IL-13 and IL-4 signaling.
The phrase “anti-IL4Ra antibody” in claims 2, 3, and 6, and the phrase “an antibody or antigen binding fragment thereof that binds to IL-4Ra” in claim 30 are also not sufficient to overcome the lack of written description for the genera of agents that inhibit IL-13 and IL-4 signaling.
It is noted that claims 2, 3, 6, and 7 recite dupilumab as an exemplary agent that inhibit IL-13 and IL-4 signaling in “such as” and/or “e.g.” clauses. However, these claims still do not recite sufficient structure because, as the claim currently reads, the agent may not be dupilumab.
Claim 34 is the only claim that recites sufficient structure for the genera of agents that inhibit IL-13 and IL-4 signaling.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, January 5, 2001, see especially page 1106 column 3). In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted:
“A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”
Regarding the claims that are drawn to a subgenera of agents that inhibit IL-13 and IL-4 signaling, wherein the agents are antibodies, artisans are well aware that knowledge of a given antigen (for instance IL-13 and/or IL-4) provides no information concerning the sequence/structure of antibodies that bind the given antigen. For example, Edwards et al. (J. Mol. Biol., 2003, 334:103-118) teach that over 1,000 different antibodies to a single protein can be generated, all with different sequences spanning almost the entire heavy and light chain germline repertoire (42/49 functional heavy chain germlines and 33 of 70 V-lambda and V-kappa light chain germlines, and with extensive diversity in the HCDR3 region sequences (that are generated by VDJ germline segment recombination) as well, see entire document).
As such, it does not seem possible to predict the sequence/structure of an antibody that binds a given antigen, as there does not appear to be any common or core structure present within all antigen binding molecules that gives rise to the function of antigen binding. Further, given data, such as that of Edwards et al., indicating the diversity of sequences in a population of antibodies that bind to a given antigen, no number of species appears to reasonably representative of the breadth of the genus of antibodies or antigen binding molecules that bind the given antigen.
It should be pointed out that it is well established in the art that the formation of an intact antigen-binding site requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three different complementarity determining regions, CDR1, 2 and 3, which provide the majority of the contact residues for the binding of the antigen binding molecule to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin (Janeway Jr et al., Immunology, 3rd Edition, 1997 Garland Publishing Inc., pages 3:1-3:11.see entire selection).
Thus, based upon the prior art, skilled artisans would reasonably understand that it is the structure of the CDRs within an antibody which gives rise to the functional property of antigen binding, the epitope to that which said CDRs bind is an inherent property which appears to necessarily be present due to conservation of critical structural elements, namely the CDR sequences themselves.
This applies to the instant invention which is drawn to a subgenera of agents that inhibit IL-13 and IL-4 signaling, wherein the agents are antibodies.
Regarding the subgenera of agents that that inhibit IL-13 and IL-4 signaling which are not antibodies, namely those that are small molecules or IL-4 muteins, the same logic applies. Small molecules and IL-4 muteins that inhibit IL-13 and IL-4 signaling still require very precise structure in order confer binding function.
As noted above, the Applicant has disclosed that the agent that inhibits IL-13 and IL-4 signaling may be an antibody or antigen binding fragment thereof, an antibody or antigen binding fragment thereof that binds to IL-4Ra, dupilumab, a small molecule inhibitor, or an IL-4 mutein. The only agent that the Applicant has disclosed which has sufficient structure is dupilumab.
Such a disclosure does not serve to provide sufficient written description of the claimed to genera of agents that inhibit IL-13 and IL-4 signaling. The disclosure does not identify sufficient structural features or combination of features which give rise to the function of inhibiting IL-13 and IL-4 signaling. Additionally, there does not appear to be any reasonable shared structure present in the genera of agents which gives rise to their functional activity. Ultimately, identifying an agent on the basis of inhibiting IL-13 and IL-4 signaling rather than by identifying the sequence/structure, namely a complete set of six CDRs for an antibody, of the agent in question is generally insufficient to provide written description.
Therefore, in view of the breadth of the claims and the limited disclosure, artisans would reasonably conclude that applicant was not in possession of the full breadth of agents that inhibit IL-13 and IL-4 signaling as encompassed by the claims at the time the instant application was filed.
Amending the claims to limit the agent that inhibits IL-13 and IL-4 signaling to dupilumab, not in a “such as” or “e.g.” clause, would obviate this part of the rejection.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claims 2, 3, 6-8, 11, 28-30, and 33-38 are rejected under 35 U.S.C. 103 as being unpatentable over Tubau and Puig 2021 (Immunotherapy, 13(4), 327–344) in view of Linder et al. 2021 (JEADV. 35(3); e192-e194, an IDS reference filed 12/04/2023).
Independent claim 2 is drawn to a method for treating moderate-to-severe or severe atopic dermatitis (AD) in a subject in need thereof, wherein the AD is inadequately controlled by an agent that inhibits IL-13 and IL-4 signaling or wherein the subject has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signaling, wherein the method comprises the step of administering the IL-13 binding protein to the subject subcutaneously, wherein the IL-13 binding protein is tralokinumab and wherein the treatment comprises the steps of: (a) administering a first dose of about 600 mg of the IL-13 binding protein to the subject; and (b) administering one or more secondary dose(s) of about 300 mg of the IL-13 binding protein to the subject, wherein each secondary dose is administered to the subject about 2 weeks or about 4 weeks after the immediately preceding dose, and wherein the treatment is carried out for at least 2 weeks.
Dependent claim 3 limits the method to that wherein the method comprises the step of selecting a subject in which AD is inadequately controlled by an agent that inhibits IL-13 and IL-4 signaling.
Dependent claim 6 limits the method to that wherein the method comprises the step of selecting a subject who has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signaling.
Dependent claim 7 limits the agent that inhibits IL-13 and IL-14 signaling to that which does not result in >75% improvement of Eczema Area and Severity Index (EASI-75) compared to baseline.
Dependent claim 8 limits the AD to which is also inadequately controlled by cyclosporine A.
Dependent claim 11 limits the method to that which is carried out for at least 2 weeks, at least 3 weeks, at least 12 weeks, at least 3 months, at least 16 weeks, at least 24 weeks, at least 26 weeks, at least 6 months, at least 32 weeks, at least 36 weeks, at least a year, or at least 52 weeks or more.
Dependent claim 28 limits the method to that wherein the IL-13 binding protein is administered as a monotherapy.
Dependent claims 29 and 30 limits the method to that wherein the IL-13 binding protein is administered in combination with a second therapeutic agent selected from the group consisting of a topical corticosteroid, a topical calcineurin inhibitor, an anti-histamine, an emollient, or an anti-bacterial therapeutic. Dependent claim 30 further limits topical corticosteroid.
Dependent claim 33 limits the method to that wherein the agent that inhibits IL-13 and IL-4 signaling is an antibody or antigen binding fragment thereof that binds to IL-4Ra.
Dependent claim 34 limits the method to that wherein the agent that inhibits IL-13 and IL-4 signaling is dupilumab.
Dependent claim 35 limits the method to that wherein the method achieves >50% improvement of Eczema Area and Severity Index (EASI-50) compared to baseline.
Dependent claim 36 limits the method to that wherein the method achieves >75% improvement of Eczema Area and Severity Index (EASI-75) compared to baseline.
Dependent claim 37 limits the method to that wherein the method achieves >75% improvement of Eczema Area and Severity Index (EASI-75) compared to baseline at week 16.
Dependent claim 38 limits the method to that wherein the method achieves >75% improvement of Eczema Area and Severity Index (EASI-75) compared to baseline at week 26.
Regarding claims 2 and 11, Tubau and Puig teach method for treating moderate-to-severe or severe atopic dermatitis (AD) in a subject in need thereof by administering tralokinumab at a first dose of about 600 mg followed by one or more secondary dose(s) of about 300 mg, wherein teach secondary dose is administered above 2 weeks or about 4 weeks after the immediately preceding dose, and wherein the treatment is carried out for at least 2 weeks (e.g. see page 335, sixth paragraph).
It is noted that tralokinumab is a human IgG4 mAb that specifically binds to IL-13 with very high affinity and neutralizes its effects (e.g. see page 335, third paragraph).
Regarding claim 8, Tubau and Puig also teach that tralokinumab ca be used in patients with severe AD who were not controlled or had contraindications to oral cyclosporin A (e.g. see paragraph spanning pages 335 and 336).
Regarding claim 28, Tubau and Puig also teach that tralokinumab can be administered as a monotherapy (e.g. see page 335, sixth paragraph).
Regarding claims 29 and 30, Tubau and Puig also teach that tralokinumab can be administered in combination with a topical corticosteroid (TCS) (e.g. see page 335, sixth paragraph).
Regarding claims 35-38, Tubau and Puig also teach that the method achieved ASI-75 at week 16 which was maintained at week 52 (e.g. see page 335, sixth paragraph).
Further regarding claim 2 and regarding claims 3, 6, 33, and 34, Tubau and Puig also teach that there were non-responders to treatment of atopic dermatitis with dupilumab (e.g. see paragraph spanning pages 333 and 334) and those that developed conjunctivitis in response to dupilumab (e.g. see page 334, second paragraph).
It is noted that dupilumab is a fully human IgG4 mAb directed against IL-4 receptor alpha (IL-4Rα), thus inhibiting IL-4 signaling through Type I receptor and IL-4 and IL-13 signaling via Type II receptor (e.g. see page 328, fourth paragraph). Tubau and Puig also teach that dupilumab was the first biological agent approved for treatment of AD (e.g. see page 328, fourth paragraph).
Regarding claim 7, Tubau and Puig also teach that a primary endpoint in treating AD with dupilumab is EASI-75. Therefore, a patient that is a non-responder to dupilumab would not reach EASI-75.
Tubau and Puig do not teach treating AD with tralokinumab specifically in a patient population that has had AD inadequately controlled by an agent that inhibits IL-13 and IL-4 signaling or a patient population that has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signaling.
Linder et al. teach, similarly to Tubau and Puig, that there is a population of patients that experience no or a limited response to dupilumab (e.g. see page e192, right column, first paragraph under “Analysis of non-responders to dupilumab in clinical practice: a cohort study”). Linder et al. teach also teach that non-responders to dupilumab are defined by failure to reach 50% improvement in SCORAD (SCORAD50) at month 4 (e.g. see paragraph spanning pages e192 and e193). Linder et al. teach also that an optimal response is defined as SCORAD75 at month 4 (e.g. see paragraph spanning pages e192 and e193).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Tubau and Puig to incorporate the teachings of Linder et al. to specifically treat AD with tralokinumab in a patient population that has had AD inadequately controlled by an agent that inhibits IL-13 and IL-4 signaling or a patient population that has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signaling. This is because there is a patient population that has little to no response to dupilumab or those that developed conjunctivitis in response to dupilumab (Tubau and Puig and Linder et al.) and because tralokinumab specifically binds to IL-13 with very high affinity and neutralizes its effects (Tubau and Puig).
Given the success and safety of using tralokinumab for treating moderate-to-severe or severe AD and that there is a population of patients that have little to know response to dupilumab, the first biological agent approved for treatment of AD that is an antibody that inhibits IL-4 and IL-13 signaling; it would have been obvious to one of ordinary skill in the art to specifically treat AD with tralokinumab in a patient population that has had AD inadequately controlled by an agent that inhibits IL-13 and IL-4 signaling or a patient population that has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signaling with a reasonable expectation of success.
A skilled artisan would have been motivated to find an alternative treatment for AD in patients who had little or no response or an adverse response, such as conjunctivitis, to the commonly used antibody that inhibits IL-4 and IL-13 signaling dupilumab. It would have been obvious to a skilled artisan to capture this patient population and find a successful treatment regimen, such as that taught by Tubau and Puig using tralokinumab, for treating their AD with a reasonable expectation of success.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Tubau and Puig 2021 (Immunotherapy, 13(4), 327–344) in view of Linder et al. 2021 (JEADV. 35(3); e192-e194, an IDS reference filed 12/04/2023), as applied to claim 2, and further in view of Faggioni et al. 2013 (US20130281876A1).
Dependent claim 18 limits the tralokinumab to that which is administered as a pharmaceutical composition comprising 50 mM sodium acetate buffer, 85 mM sodium chloride, 0.01% (w/v) polysorbate 80, wherein the pharmaceutical composition has a pH of 5.5.
The combined teachings of Tubau and Puig in view of Linder et al. pertaining to claim 2, and the rationale for combining them are outlined in the 103 rejection above.
The combined reference teachings do not teach that the tralokinumab is administered as a pharmaceutical composition comprising 50 mM sodium acetate buffer, 85 mM sodium chloride, 0.01% (w/v) polysorbate 80, wherein the pharmaceutical composition has a pH of 5.5.
Faggioni et al. teach that tralokinumab is formulated at 150 mg/mL in 50 mM sodium acetate, 85 mM sodium chloride, 0.01% (w/v) plant-derived polysorbate 80 at pH 5.5 (e.g. see [0031] and [0141]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined teachings of Tubau and Puig in view of Linder et al. as applied to claim 2, and incorporate the teachings of Faggioni et al. to include that the tralokinumab is administered as a pharmaceutical composition comprising 50 mM sodium acetate buffer, 85 mM sodium chloride, 0.01% (w/v) polysorbate 80, wherein the pharmaceutical composition has a pH of 5.5. This is because tralokinumab has already been successfully formulated at 150 mg/mL in 50 mM sodium acetate, 85 mM sodium chloride, 0.01% (w/v) plant-derived polysorbate 80 at pH 5.5.
Given that tralokinumab has already been successfully formulated at 150 mg/mL in 50 mM sodium acetate, 85 mM sodium chloride, 0.01% (w/v) plant-derived polysorbate 80 at pH 5.5; it would have been obvious to a skilled artisan to specifically use this formulation in the method of treating AD with tralokinumab in a specific patient population as taught by Tubau and Puig in view of Linder et al. with a reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 2, 3, 6-8, 11, 18, 28-30, and 33-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 12,187,788 (the ‘788 Patent) in view of Tubau and Puig 2021 (Immunotherapy, 13(4), 327–344) and Linder et al. 2021 (JEADV. 35(3); e192-e194, an IDS reference filed 12/04/2023).
The instant claims are drawn to a method for treating moderate-to-severe or severe atopic dermatitis (AD) in a subject in need thereof, wherein the AD is inadequately controlled by an agent that inhibits IL-13 and IL-4 signaling or wherein the subject has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signaling, wherein the method comprises the step of administering the IL-13 binding protein to the subject subcutaneously, wherein the IL-13 binding protein is tralokinumab and wherein the treatment comprises the steps of: (a) administering a first dose of about 600 mg of the IL-13 binding protein to the subject; and (b) administering one or more secondary dose(s) of about 300 mg of the IL-13 binding protein to the subject, wherein each secondary dose is administered to the subject about 2 weeks or about 4 weeks after the immediately preceding dose, and wherein the treatment is carried out for at least 2 weeks.
The claims in the ‘788 Patent are drawn to a method of treating atopic dermatitis (AD) in a subject in need thereof, wherein the method comprises the steps of: (a) administering a first dose of about 300 mg of an IL-13 binding protein to the subject; and (b) administering one or more secondary dose(s) of about 300 mg of the IL-13 binding protein to the subject, wherein each secondary dose is administered to the subject about 4 weeks after the immediately preceding dose, wherein prior to step (a) the method further comprises a step of administering a first prior dose of the IL-13 binding protein followed by one or more prior dose(s) of the IL-13 binding protein to the subject, such that each of the one or more prior dose(s) of the IL-13 binding protein is administered to the subject about 2 weeks after the immediately preceding prior dose, and wherein the IL-13 binding protein is an anti-IL-13 antibody, or an IL-13 binding fragment thereof, comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein: (i) the heavy chain variable region comprises: a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:1; a heavy chain complementarity determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO: 2; and a heavy chain complementarity determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:3; and (ii) the light chain variable region comprises: a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:4; a light chain complementarity determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:5; and a light chain complementarity determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:6.
It is noted that the anti-IL-13 antibody comprising SEQ ID NOs: 1-6 is tralokinumab (e.g. see Table 1 spanning columns 25 and 26).
The claims in the ‘788 Patent differ from the instant invention by failing to recite a 600 mg loading dose and the specific patient population of the instant invention, namely, a patient population that has had AD inadequately controlled by an agent that inhibits IL-13 and IL-4 signaling or a patient population that has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signaling.
The teachings of Tubau and Puig and Linder et al. are outlined in the 103 rejection above.
It would be obvious to one of ordinary skill in the art to modify the claims in the ‘788 Patent and to incorporate the teachings of Tubau and Puig and Linder et al. to include that the tralokinumab is administered at a 600 mg loading dose and in a specific patient population that has had AD inadequately controlled by an agent that inhibits IL-13 and IL-4 signaling and a patient population that has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signaling. This is because a 600 mg loading dose of tralokinumab has already been successfully used in a method of treating AD (Tubau and Puig) and because there is a patient population that has little to no response to dupilumab or those that developed conjunctivitis in response to dupilumab (Tubau and Puig and Linder et al.)
Given the success and safety of using tralokinumab for treating moderate-to-severe or severe AD with a 600 mg loading dose and that there is a population of patients that have little to know response to dupilumab, the first biological agent approved for treatment of AD that is an antibody that inhibits IL-4 and IL-13 signaling; it would be obvious to one of ordinary skill in the art to specifically treat AD with tralokinumab in a patient population that has had AD inadequately controlled by an agent that inhibits IL-13 and IL-4 signaling or a patient population that has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signaling and with a 600 mg loading dose with a reasonable expectation of success.
A skilled artisan would be motivated to find an alternative treatment for AD in patients who had little or no response or an adverse response, such as conjunctivitis, to the commonly used antibody that inhibits IL-4 and IL-13 signaling dupilumab. It would be obvious to a skilled artisan to capture this patient population and find a successful treatment regimen, such as that taught by Tubau and Puig using tralokinumab, for treating their AD with a reasonable expectation of success.
Therefore, the claims in the ‘788 Patent would render the instant claims obvious.
Claims 2, 3, 6-8, 11, 18, 28-30, and 33-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 4-6, 9-12, 15, 16, 20-23, 44-46, 48-51, and 53-60 of co-pending U.S. Application No. 17/913,483 (the ‘483 Application) in view of Tubau and Puig 2021 (Immunotherapy, 13(4), 327–344) and Linder et al. 2021 (JEADV. 35(3); e192-e194, an IDS reference filed 12/04/2023).
The instant claims are drawn to a method for treating moderate-to-severe or severe atopic dermatitis (AD) in a subject in need thereof, wherein the AD is inadequately controlled by an agent that inhibits IL-13 and IL-4 signaling or wherein the subject has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signaling, wherein the method comprises the step of administering the IL-13 binding protein to the subject subcutaneously, wherein the IL-13 binding protein is tralokinumab and wherein the treatment comprises the steps of: (a) administering a first dose of about 600 mg of the IL-13 binding protein to the subject; and (b) administering one or more secondary dose(s) of about 300 mg of the IL-13 binding protein to the subject, wherein each secondary dose is administered to the subject about 2 weeks or about 4 weeks after the immediately preceding dose, and wherein the treatment is carried out for at least 2 weeks.
The claims in the ‘483 Application are drawn to a method of treating atopic dermatitis (AD) in a subject in need thereof, wherein the method comprises the steps of: (a) administering an IL-13 binding protein to the subject every two weeks and then (b) administering the IL-13 binding protein to the subject every four weeks, wherein the IL-13 binding protein is an anti-IL-13 antibody, or an IL-13 binding fragment thereof, comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein:(i) the heavy chain variable region comprises :a heavy chain complementarity determining region 1 (HCDR1) comprising an amino acid sequence of SEQ ID NO:1; a heavy chain complementarity determining region 2 (HCDR2) comprising an amino acid sequence of SEQ ID NO:2; and a heavy chain complementarity determining region 3 (HCDR3) comprising an amino acid sequence of SEQ ID NO:3; and(ii) the light chain variable region comprises: a light chain complementarity determining region 1 (LCDR1) comprising an amino acid sequence of SEQ ID NO:4; a light chain complementarity determining region 2 (LCDR2) comprising an amino acid sequence of SEQ ID NO:5; and a light chain complementarity determining region 3 (LCDR3) comprising an amino acid sequence of SEQ ID NO:6.
It is noted that the anti-IL-13 antibody comprising SEQ ID NOs: 1-6 is tralokinumab (e.g. see Table 1 spanning columns 25 and 26).
The claims in the ‘483 Application differ from the instant invention by failing to recite the same dosing regimen and the specific patient population of the instant invention, namely, a patient population that has had AD inadequately controlled by an agent that inhibits IL-13 and IL-4 signaling or a patient population that has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signaling.
The teachings of Tubau and Puig and Linder et al. are outlined in the 103 rejection above.
It would be obvious to one of ordinary skill in the art to modify the claims in the ‘483 Application and to incorporate the teachings of Tubau and Puig and Linder et al. to include that the tralokinumab is administered at the claimed dosing regimen and in a specific patient population that has had AD inadequately controlled by an agent that inhibits IL-13 and IL-4 signaling and a patient population that has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signaling. This is because the claimed dosing regimen of tralokinumab has already been successfully used in a method of treating AD (Tubau and Puig) and because there is a patient population that has little to no response to dupilumab or those that developed conjunctivitis in response to dupilumab (Tubau and Puig and Linder et al.)
Given the success and safety of using tralokinumab for treating moderate-to-severe or severe AD with the claimed dosing regimen and that there is a population of patients that have little to know response to dupilumab, the first biological agent approved for treatment of AD that is an antibody that inhibits IL-4 and IL-13 signaling; it would be obvious to one of ordinary skill in the art to specifically treat AD with tralokinumab in a patient population that has had AD inadequately controlled by an agent that inhibits IL-13 and IL-4 signaling or a patient population that has experienced conjunctivitis when treated with an antibody that inhibits IL-4 and IL-13 signaling and with the claimed dosing regimen with a reasonable expectation of success.
A skilled artisan would be motivated to find an alternative treatment for AD in patients who had little or no response or an adverse response, such as conjunctivitis, to the commonly used antibody that inhibits IL-4 and IL-13 signaling dupilumab. It would be obvious to a skilled artisan to capture this patient population and find a successful treatment regimen, such as that taught by Tubau and Puig using tralokinumab, for treating their AD with a reasonable expectation of success.
Therefore, the claims in the ‘483 Application would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/GRACE H LUNDE/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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