Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
The amendment after non-final office action filed November 21, 2025 is acknowledged. Claims 4-5, 7-26 were cancelled, claims 1 and 29 were amended, claims 1-3, 6, 27-30 are pending.
*After further review, a new rejection under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is presented below due to amendment and thus, a second Non-final follows.
Election/Restrictions
The restriction requirement sent out on July 6, 2022 was previously withdrawn in view of amendment of the claims to combine inventions.
Claims 1-3, 6, 27-30 are examined on the merits of this office action.
Withdrawn Objections/Rejections
The rejection of claim(s)1-3, 6, 27-30 are rejected under 35 U.S.C. 103 as being unpatentable over Madan ( Madan et al. BMC Nephrology (2016) 17:37, cited previously) in view of Lal (Volume56, Issue2, February 2016, Pages 195-202, cited in Applicant’s IDS) and Bombacher (Z Klin. Chem. U. Klin, Biochem, pages 291-292, 1969, cited in Applicant’s IDS) is withdrawn in view of amendment of the claims filed November 21, 2025.
The rejection of claims 29-30 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of amendment of the claims filed November 21, 2025.
The rejection of claim(s) 1-3, 6, 29-30 under 35 U.S.C. 102(a)(1) as being anticipated by Madan (BMC Nephrology (2016) 17:37, cited previously) is withdrawn in view of amendment of the claims filed November 21, 2025.
*Applicant’s arguments are moot in light of amendment of the claims, removal of the previous rejection and the new rejection under 35 U.S.C 103 presented below.
New Objections
Claim 27 is objected to for the following informality: the limitation “wherein after administration of the non-synthetic adrenal corticotropin composition, the subject has…” The limitation of “the subject” should be replaced with -the one or more subject-.
Similarly, Claim 28 should be amened to replace the limitation of “the subject” with -the one or more subject-.
New Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 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 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 1-3, 6, 27-30 are rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement (new matter). The claim(s) contain 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(s), at the time of the application was filed, had possession of the claimed invention.
The claims are drawn to “A method of administering an adrenal corticotropin treatment for subjects in need of such treatment, the method comprising: testing the subjects to identify one or more subjects that are responsive to steroid therapy and one or more subjects that are not responsive to steroid therapy; administering to the one or more of the subjects that are responsive to steroid therapy an adrenal corticotropin treatment consisting essentially of a synthetic adrenal corticotropin composition comprising a synthetic ACTH1-24 depot to induce a delayed corticosteroid response i; and administering to the one or more of the subjects that are not responsive to steroid therapy an adrenal corticotropin treatment consisting essentially of a non-synthetic adrenal corticotropin composition comprising a repository corticotropin injection (RCI) of a naturally sourced complex mixture comprising N-25 deamidated porcine ACTH1-39 to induce a non-delayed corticosteroid response, wherein the delayed corticosteroid response is appropriate when the subject is responsive to steroid therapy, wherein the non-delayed corticosteroid response is appropriate when the subject does not show improvement of one or more clinical factors when steroid therapy is provided at maintenance doses used to treat nephrotic syndrome, wherein the delayed corticosteroid response causes a peak corticosteroid blood concentration at least 8 hours after administration of the adrenal corticotropin treatment, and wherein the non-delayed corticosteroid response causes a peak corticosteroid blood concentration less than 8 hours after administration of the adrenal corticotropin treatment”. Claim 29 additionally claims “test the patients to identify one or more patients responsive to steroid therapy and one or more patients that are not responsive to steroid therapy…”
Applicant’s specification states “In some embodiments, a strong corticosteroid response is beneficial when the subject is responsive to steroid therapy. In contrast, in other embodiments, a strong corticosteroid response is not beneficial when the subject is substantially not responsive to steroid therapy. As used herein, “substantially not responsive” means that at typical dosages and administration schedules, a subject does not show improvement of one or more clinical factors (see paragraph 0140). Nowhere in Applicant’s specification do they discuss or provide support for testing patients to identify responsiveness to steroid therapy and then administering the composition. Applicants further state that “Baseline demographics were collected during the screening period between study Day −28 and Day −3” (paragraph 0152). There is no guidance or support for the active method step of testing patients to identify responsiveness to steroid therapy.
Lack of Ipsis Verbis Support
The specification is void of any literal support “testing the subjects/patients to identify one or more subjects that are responsive to steroid therapy and one or more subjects that are not responsive to steroid therapy". Applicant’s specification states “Applicant’s specification states “In some embodiments, a strong corticosteroid response is beneficial when the subject is responsive to steroid therapy. In contrast, in other embodiments, a strong corticosteroid response is not beneficial when the subject is substantially not responsive to steroid therapy. As used herein, “substantially not responsive” means that at typical dosages and administration schedules, a subject does not show improvement of one or more clinical factors (see paragraph 0140). Nowhere in Applicant’s specification do they discuss or provide support for testing patients to identify responsiveness to steroid therapy and then administering the composition. Applicants further state that “Baseline demographics were collected during the screening period between study Day −28 and Day −3” (paragraph 0152). There is no guidance or support for the active method step of testing patients to identify responsiveness to steroid therapy.
An ordinary-skilled artisan cannot clearly envisage the active method steps of testing subjects/patients to identify one or more subjects that are responsive to steroid therapy and one or more subjects that are non-responsive to steroid therapy based on the specification. Thus, such limitations recited in the present claims, which did not appear in the specification, as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C. §112. Applicant is required to cancel the new matter in the response to this Office Action. Alternatively, applicant is invited to provide sufficient written support for the “limitations” indicated above. See MPEP §714.02, §2163.05-06 and §2173.05(i).
Lack of Implicit or Inherent Support
“While there is not in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure.” See MPEP 2163. Thus support can be furnished implicitly or inherently for a specifically claimed limitation. However, the specification lacks any implicit or inherent support for the claimed active step limitation “testing the subjects or patients to identify one or more subjects that are responsive to steroid therapy and one or more subjects that are non- responsive..”. As explained supra, there is no support in the specification for this step.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
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, 28 and 30 is 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 2 recites “the corticosteroid response”, however claim 1 introduces both a delayed corticosteroid response and a non delayed corticosteroid response. Therefore, it is unclear whether the limitation in claim 2 refers to the delayed corticosteroid response, the non-delayed corticosteroid response, or both responses. Accordingly, the claim lacks antecedent basis. Claim 3 is also rejected due to its dependence on claim 2 and not further clarifying this point of confusion.
Claim 6 claims “The method of claim 1, wherein the subject is diagnosed with an autoimmune disorder”. However, claim 1 claims multiple subjects, one or more subjects that are responsive to steroid therapy and one or more subjects that are not responsive to steroid therapy. Because of this, the term “the subject” in claim 6 does not have a clear antecedent basis and thus lacks proper antecedent basis.
Claim 28 claims “the subject has a 5-fold lower plasma free cortisol exposure than the synthetic adrenal corticotropin composition after 2 doses”. It is unclear whether “after 2 doses” refers to administration of the synthetic adrenal corticotropin composition, the non synthetic adrenal corticotropin composition, or both. Accordingly the scope of the comparison is unclear and the claim is indefinite.
Claim 30 recites the limitation "the patient" in line 1. However, claim 29 (from which claim 30 depends on) was amended to recite “patients” and “one or more patients” and does not identify a singular patient. Furthermore, it is unclear whether “the patient” in claim 30 refers a steroid responsive patient, a steroid non responsive patient or both making the scope unclear. There is insufficient antecedent basis for this limitation in the claim.
A suggested amendment of the claim could be “wherein the one or more patients that are not responsive to steroid therapy are….”
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The 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.
Claim(s)1-3, 6, 27-30 are rejected under 35 U.S.C. 103 as being unpatentable over Madan ( Madan et al. BMC Nephrology (2016) 17:37, cited previously) in view of BERG (Nephrol Dial Transplant (2004) 19: 1305–1307), Lal (Volume56, Issue2, February 2016, Pages 195-202, cited in Applicant’s IDS) and Bombacher (Z Klin. Chem. U. Klin, Biochem, pages 291-292, 1969, cited in Applicant’s IDS).
Regarding claims 1 and 29, Madan teaches a method of administering an adrenal corticotropin treatment for a subject in need of such treatment. Specifically, Madan discloses administration of repository corticotropin injection (RCI; H.P. Acthar Gel, porcine ACTH1-39) to patients with nephrotic syndrome who are resistant to steroid therapy (Abstract, Methods; Conclusions). Thus, Madan teaches administering a non-synthetic adrenal corticotropin composition comprising a repository corticotropin injection of porcine ACTH1-39 when the subject does not respond to steroid therapy. This corresponds to the claimed administration when a non-delayed corticosteroid response is appropriate. Identifying a patient as steroid resistant necessarily requires evaluating the patients responsiveness to steroid therapy. Thus, the testing step recite in the claim is inherent in the identification of steroid resistant patients (see MPEP 2112). Furthermore, with respect to the limitation of testing subjects or patients to identify steroid responsive and steroid non responsive subjects (claims 1 and 29), identifying a patient as steroid resistant necessarily requires a testing or assessing the patient for responsiveness to steroid therapy. The claims do not recite any specific testing methodology, biomarker, assay or diagnostic threshold. Accordingly, under the broadest reasonable interpretation, routine clinical assessment of steroid treatment response or failure, as taught by Madan, satisfies the setting limitation.
Madan is silent to administration of a synthetic adrenal corticotropin composition comprising a synthetic ACTH 1-24 depot to subjects responsive to steroid therapy as recited in the claim.
However, Berg teaches treatment of nephrotic syndrome patients using Synacthen Depot (ACTH1-24), which is a synthetic ACTH analogue administered in Depot form (Berg, introduction; Methods, Table 1). Berg reports administration of ACTH1-24 depot to nephrotic patients with a variety of diagnosis. Berg further explains that ACTH therapy had historically been used in the treatment of nephrotic syndrome as an alternative to corticosteroid therapy because ACTH stimulates endogenous corticosteroid production (Berg, introduction). Thus, Berg teaches administration of a synthetic adrenal corticotropin composition comprising synthetic ACTH1-24 depot to nephrotic patients, including patients not identified as steroid resistant, corresponding to the claimed administration to subject responsive to steroid therapy.
Lal teaches that repository corticotropin injection (ACTH analogue) stimulates corticosteroid production through activation of melanocortin receptor-2 (MC2R) in the adrenal cortex, resulting in secretion of glucocorticoids including cortisol. Lal further teaches that administration of ACTH analogues results in increase in plasma cortisol concentrations within hours of administration (Lal Figure 1B, less than 10 hours).
Bombacher further teaches that porcine ACTH1-39 produces a more rapid cortisol response than ACTH1-24, while ACTH1-24 depot produces a delayed and sustained release profile.
It would have been obvious before the effective filing date of the claimed invention to select between synthetic ACTH1-24 depot and porcine ACTH1-39 RCI based on the clinical characteristics of the patient and the desired corticosteroid response profiled. Madan teaches administration of porcine ACTH1-39RCI for treatment of nephrotic patients who are resistant to steroid therapy. Berg teaches administration of synthetic ACTH1-24 depot for treatment of nephrotic patients, including patients not identified as steroid resistant. Lal and Bombacher further teach that ACTH1-39 produces a more rapid increase in cortisol levels whereas ACTH1-24 depot produces a delayed sustained corticosteroid response. Accordingly, one of ordinary skill in the art would have been motivated to administer ACTH1-24 depot to patients responsive to steroid therapy where a sustained corticosteroid response is desired, and to administer ACTH1-39RCI to patients not responsive to steroid therapy where a more rapid corticosteroid responsive is desired, with a reasonable expectation of success based on the known pharmacokinetic differences between these ACTH formulations as taught by Lal and Bombacher.
Furthermore, one of ordinary skill in the art would have been motivated to do so to produce a quick, more consistent response in patients that are already resistant to first line of treatments and thus, in need of a quick therapeutic effect. There is a reasonable expectation of success given that both Lal and Bombacher teach a more rapid increase (less than 8 hours) in cortisol response to treatment with ACTH1-39 (a mechanism in which ACTH imparts its therapeutic effects).
Regarding claim 2, Madan teaches that ACTH analogues act via MC2R in the adrenal cortex to stimulate steroidogenesis, including glucocorticoids (Background, citing known ACTH pathways).
Regarding claim 3, It is well established that ACTH stimulation of the adrenal cortex results in secretion of cortisol as the principal glucocorticoid in humans. Administration of RCI in Madan therefore inherently produces a cortisol response. Inherency does not require recognition in the art, only that the limitation is necessarily present (see MPEP 2112).
Regarding claim 6,Madan teaches use of RCI for nephrotic syndrome, including subpopulations with lupus nephritis (an autoimmune disorder))(see Madan, Table 1, reporting Acthar treatment in lupus patients with nephrotic syndrome).
Regarding claims 27-28, Lal and Bombacher show that ACTH1-39 produces a more rapid but lower amplitude peak cortisol response compared to ACTH1-24 depot. Thus, the limitations of “the subject having a greater than two fold lower mean peak baseline corrected plasma free cortisol as compared to administration of the synthetic adrenal corticotropin” and “5 fold lower plasma free cortisol exposure than the synthetic adrenal corticotropin after two doses”, these are inherent pharmacokinetic properties of the two treatments, and it would have been obvious to expect this comparative outcome based on the teachings of the prior art.
Claim 29 recites substantially similar limitations as in claim 1, including testing patients for steroid responsiveness and administering synthetic ACTH1-24 depot to steroid responsive patients and non synthetic ACTH1-39 repository corticotropin injection to steroid non responsive patients. Accordingly, the combination of Madan, Berg, Bombacher and Lal teaches or suggests the limitations of claim 29 for the same reasons as discussed above.
Regarding claim 30, Madan teaches administration of RCI Acthar gel for treatment of nephrotic syndrome patients who are steroid resistant (Madan, Methods and Conclusions). Acthar gel is naturally sourced porcine ACTH preparation containing ACTH1-39, corresponding to the claimed non synthetic adrenal corticotropin composition comprising a repository corticotropin injection of porcine ACTH1-39. Therefore, Madan teaches or suggests the additional limitation of claim 30.
Conclusion
No claims are allowed.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654