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 July 10, 2026 is acknowledged.
Claims 4-5, 7-28 are cancelled, claims 1-2, 29-30 were amended and claims 1-3, 6, 29-30 are pending.
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The restriction requirement sent out on July 6, 2022 was previously withdrawn in view of amendment of the claims to combine inventions.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, 29-30 are examined on the merits of this office action.
Withdrawn Rejections
The rejection of 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under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement (new matter) is withdrawn in view of amendment of the claims filed July 10, 2026.
The rejection of claims 2-3, 6, 28 and 30 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of amendment of the claims filed July 10, 2026.
Maintained Revised Rejections
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, 29-30 remain 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).
The claimed “strong corticosteroid response” is understood in light of the specification as referring to a corticosteroid response characterized as a non-dose dependent, delayed, and having a high daily steroid equivalent dose (see paragraph 0139) and indicates that such a response is beneficial in a patient responsive to steroid therapy (see paragraph 0140). Thus, the claimed strong corticosteroid response is consistent with the delayed response associated with ACTH1-24 depot and the selection of such treatment for a steroid responsive patient.
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 to a subject that does not respond to steroid therapy. As amended, claims 1 and 29 no longer require testing subjects or patients to identify steroid responsiveness. Rather, the claims require determining whether a delayed corticosteroid response or a non-delayed corticosteroid response is appropriate for the subject, selecting between synthetic or non-synthetic treatments and administering the selected treatment. Madan teaches treatment of steroid resistant nephrotic syndrome patients with RCI. Madan therefore teaches or suggests the claimed non-responsive patient circumstance and provides the patients known clinical response to steroid therapy as a basis for selecting an appropriate treatment.
Madan is silent to administration of a synthetic adrenal corticotropin composition comprising a synthetic ACTH 1-24 depot to subjects when a delayed corticosteroid response is appropriate and wherein the subjects are 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). Berg further teaches that ACTH can be used when steroid treatment is indicated (see last page, last paragraph). Although Berg reports that 11 patients had previously received steroids without response, the remaining patients are not reported as having failed steroid therapy (see Table 1). Thus, Berg demonstrates that synthetic ACTH1-24 depot was a known treatment for nephrotic syndrome and recognizes its use in circumstances in which steroid treatment is indicated.
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.
Thus, the prior art teaches the differing corticosteroid response profiles of the claimed treatment alternatives. In particular, synthetic ACTH1-24 depot provides a delayed and sustained response, whereas ACTH1-39 provides a comparatively rapid, non delayed response.
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.
With respect to the claimed temporal limitations, Bombacher and Lal teach or suggest the differing timing of the corticosteroid responses resulting from the different treatments. Wherein the cited data establish the claimed peak corticosteroid blood concentrations of at least 8 hours for ACTH1-24 depot and less than 8 hours for ACTH1-39, the temporal limitations reflect the known response profiles (inherent pharmacokinetic profiles) of the respective treatments.
Furthermore, the known response profiles, and the patients known response to steroid therapy provide a rational basis for making the claimed selection. The motivation to for making the claimed selection need not be identical to Applicant’s stated reason for determining that a strong corticosteroid response is beneficial or not beneficial. It is sufficient that the prior art provides a reasons with rational underpinning to make the claimed selection with a reasonable expectation of success. The claimed characterization of the resulting response as beneficial or not beneficial does not render the selection nonobvious wherein the underlying patient characteristics and response profiles were known in the art.
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).
Claim 29 recites substantially similar limitations as in claim 1, including determining whether a delayed corticosteroid response or a non-delayed corticosteroid response is appropriate for the patient, selecting between synthetic or non-synthetic treatments and administering the selected treatment.
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 the limitation of a peak corticosteroid blood concentration at at least 8 hours or less than 8 hours depending on the treatment (claims 1 and 29), 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 “peak corticosteroid of at at least 8 hours for the synthetic treatment and “less than 8 hours” for the non-synthetic treatment, are considered 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.
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.
Response to Applicant’s Arguments
Applicants argue that “Claim 1 has been amended to recite, inter alia, "determining whether a delayed corticosteroid response or a non-delayed corticosteroid response is appropriate for the subject; based on the determination, selecting...and administering the selected adrenal corticotropin treatment to the subject." As amended, the claimed method recites an affirmative treatment-selection process involving the two recited treatment options. Applicant respectfully submits that Madan, Lal, and Bombacher fail to disclose, teach, or suggest determining whether a delayed corticosteroid response or a non- delayed corticosteroid response is appropriate for the subject/patient; based on that determination, selecting between the synthetic ACTH1-24 depot treatment and the non- synthetic RCI treatment; and administering the selected adrenal corticotropin treatment, as recited by independent claim 1.
Madan does not teach or suggest any kind of determining whether a delayed corticosteroid response or non-delayed corticosteroid response is appropriate for a subject, selecting between synthetic ACTH1-24 depot and RCI based on that determination, and then administering the selected treatment. The Examiner alleges "Madan discloses administration of repository corticotropin injection ... to patients with nephrotic syndrome who are resistant to steroid therapy." Office Action, p. 8. The Examiner points to the entirety of Madan for this alleged disclosure. However, Madan is not concerned with steroid-resistant patients. Rather, Madan is concerned with identifying a treatment for nephrotic syndrome generally, without accounting for different treatments based on steroid responsiveness. Even accepting that Madan identifies steroid-resistant patients, that is not the same as determining whether a delayed or non-delayed corticosteroid response is appropriate and selecting between the two recited ACTH treatment options.
The Examiner admits that "Madan is silent to administration of a synthetic corticotropin composition comprising a synthetic ACTH 1-24 depot to subjects responsive to steroid therapy as recited in the claim." Office Action, p. 8. Further, Madan does not even mention synthetic ACTH1-24. The Examiner relies on Berg, Lal, and Bombacher to allegedly teach administration of a synthetic ACTH1-24 depot to subjects that are responsive to steroid therapy. Berg, at most, discloses administration of synthetic ACTH1-24 depot to nephrotic syndrome patients. Berg does not teach selecting between synthetic ACTH1-24 depot and RCI based on a determination that a delayed or non-delayed corticosteroid response is appropriate.
The Examiner appears to reason that Berg's patients include patients "not identified as steroid resistant," and therefore correspond to steroid-responsive patients. Applicant respectfully disagrees. A patient "not identified as steroid resistant" is not necessarily a patient determined to be steroid responsive, much less a patient for whom a delayed corticosteroid response or strong corticosteroid response has been determined to be beneficial. Berg does not disclose the claimed determination or selection between two treatment options and does not provide a reason to use steroid responsiveness or strong corticosteroid response to choose between synthetic ACTH1-24 depot and RCI. Lal relates to a comparison of repository corticotropin injections (porcine adrenocorticotropic hormone [ACTH] analog) and intravenous methylprednisolone (IVMP). Lal does not even mention a synthetic ACTH1-24 depot at all. In fact, Lal is entirely silent in regard to treating patients with the two claimed compositions based on steroid responsiveness. Bombacher teaches away from the method of independent claim 1. First, Bombacher is specifically concerned with finding an alternative to highly purified natural (i.e., non-synthetic) ACTH. In fact, Bombacher disparages the use of naturally occurring ACTH stating, "there was always the danger of sensitizing the patient towards the animal protein with all the unwanted consequences such as anaphylactic shock in all its forms." Bombacher, p. 1. Thus, one of skill in the art looking to Bombacher would have been discouraged from administering the repository corticotropin injection of independent claim Furthermore, Bombacher teaches "the duration of action of the synthetic product was much shorter than the natural hormone." Bombacher, p. 1. Bombacher specifically teaches that synthetic ACTH1-24 produces a non-delayed response. In fact, Bombacher specifically teaches that the action of the synthetic ACTH1-24 depot is much shorter than the non-synthetic ACTH1-39. Thus, one of skill in the art looking to Bombacher would be taught the exact opposite of what is claimed by independent claim 1, where the synthetic ACTH1-24 depot is administered to induce a delayed corticosteroid response in subjects that are responsive to steroid therapy.
Therefore, both Lal and Bombacher do not teach that a delayed corticosteroid response is appropriate when a strong corticosteroid response is beneficial, nor that a non-delayed corticosteroid response is appropriate when a strong corticosteroid response is not beneficial. Thus, Lal and Bombacher fail to remedy the deficiencies of Madan and Berg.
The Examiner concludes that it would have been obvious to select between synthetic ACTH1-24 depot and RCI based on clinical characteristics and desired corticosteroid response profile. Applicant respectfully submits that this conclusion is based on impermissible hindsight.
The cited art does not teach the claimed decision rule. The Office Action uses Applicant's own disclosure as a roadmap to combine the disparate teachings of the cited art into a treatment-selection method in which a practitioner determines whether a delayed or non-delayed corticosteroid response is appropriate and then selects between the two recited ACTH treatment options. The Office Action further states that a person of ordinary skill would have been motivated to administer RCI to steroid-resistant patients to produce a quick therapeutic effect. That rationale is not the rationale of the claims. The claimed method recites determining whether a delayed or non-delayed corticosteroid response is appropriate and selecting the ACTH treatment accordingly. In particular, the claims recite that a non- delayed corticosteroid response is appropriate when a strong corticosteroid response is determined not to be beneficial, including 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. The cited art does not teach the claimed determination or selection.
Applicant’s arguments have been fully considered but not found persuasive. IN response to Applicants argument that Madan, Berg, Lal and Bombacher fail to teach or suggested the method of the instant claims is not persuasive. The rejection is based on the combined teachings of the references, not any single reference disclosing the claimed method in its entirety. MPEP 2145 “One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Where a rejection of a claim is based on two or more references, a reply that is limited to what a subset of the applied references teaches or fails to teach, or that fails to address the combined teaching of the applied references may be considered to be an argument that attacks the reference(s) individually. Where an applicant’s reply establishes that each of the applied references fails to teach a limitation and addresses the combined teachings and/or suggestions of the applied prior art, the reply as a whole does not attack the references individually as the phrase is used in Keller and reliance on Keller would not be appropriate. This is because "[T]he test for obviousness is what the combined teachings of the references would have suggested to [a PHOSITA]." In re Mouttet, 686 F.3d 1322, 1333, 103 USPQ2d 1219, 1226 (Fed. Cir. 2012). Madan teaches RCI treatment of steroid resistant nephrotic syndrome patients; Berg teaches synthetic ACTH1-24 depot treatment of nephrotic syndrome patients; and Lal and Bombacher teach of corticosteroid response characteristics associated with ACTH treatment.
Applicant argues that Mada does not teach the claimed determination and selection. Madan is not relied upon for the entire selection process. Rather, Madan teaches use of RCI in steroid resistant nephrotic syndrome patients and therefore establishes steroid responsiveness as a known clinical circumstance relevant to treatment. Applicant further argues that Bergs patients “not identified as steroid resistant” cannot be equated with steroid responsive patients. Berg is relied upon for teaching synthetic ACTH1-24 depot as a known treatment for nephrotic syndrome, not for establishing that patients not identified as steroid resistant were necessarily steroid responsive. Berg treated 23 patients with ACTH1-24 depot; 11 of which had previously received steroids without response, while the remaining patients are not reported as having received and failed steroid therapy. Berg further teaches that “ACTH can obviously be used when steroid treatment is indicated”.
Applicant argues that Lal does not disclose ACTH1-24 depot or the claimed selection process. Lal is not relied upon for those teachings alone, but for its teachings concerning ACTH induced corticosteroid production and corticosteroid response characteristics. References relied upon in an obviousness combination need not individually disclose every claim limitation. Applicant further argues that Bombacher teaches away because it discusses disadvantages of naturally occurring ACTH and states that the synthetic product has a shorter duration of action than natural ACTH. These arguments are not persuasive. Madan independently demonstrates therapeutic use of naturally source porcine ACTH1-39 RCI despite the disadvantages identified by Bombacher. Further, duration of action is not necessarily the same as time to peak corticosteroid concentration, which the temporal characteristic recited by the claims. Thus, Bombacher’s statement concerning duration does not alone establish teaching away from the claimed peak response timing.
Applicant further argues that the references fail to teach whether a “strong corticosteroid response” is beneficial. The specification describes a strong corticosteroid response as including a delayed response and indicates that such a response is beneficial when the patient is responsibe to steroid therapy (paragraph 0139-0140). The cited art teaches the underlying ACTH treatments, corticosteroid response characteristics, and relevance of prior steroid response upon which the claimed determination is based.
Applicant argues that the Examiners rationale constitutes hindsight and administering RCI to obtain a more rapid response is not Applicant’s rationale for the claimed selection. This argument is not persuasive. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Furthermore, the motivation supporting an obviousness combination need not be the same motivation or purpose identified by Applicant. The relevant inquiry is whether the prior art as a whole provides a reason with rational underpinning to make the claimed selection with a reasonable expectation of success.
Madan teaches RCI treatment of steroid resistant nephrotic patients, Berg teaches ACTH1-24 depot as a treatment for nephrotic syndrome, and Lal and Bombacher teach relevant corticosteroid response characteristics. Collectively, these teachings would have provided one of ordinary skill reason select between known ACTH treatments based on the patients clinical circumstances and the desired corticosteroid response profile. Importantly, the amended claim do not require a separate test for steroid responsiveness, nor do they require administering both treatments in a single performance of the method. Rather, the claims require determining the appropriate response, selecting between the treatment alternatives based on the determination, and administering the selected treatment.
The claims recite a conditional treatment selection method do not require administration of both recited treatments or treatment of both patient populations. Rather, based on the determination of which response is appropriate, one of the two recited treatment is selected and administered. Thus, the prior art does not need to disclose simultaneous or actual administration of both treatments.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654
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