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
Continued Examination Under 37 CFR 1.114
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicants’ submission filed on 7/14/2026 has been entered.
Status of the Claims
2. Claims 1-26 are the original claims filed 8/26/2022. In the Preliminary Amendment of 8/26/2022, claims 1-25 are amended and claim 26 is canceled. In the Reply of 8/7/2025, claims 1-25 are amended. In the Response of 3/23/2026, claims 1-2, 9, 11-12, 14-15, and 18-25 are amended, and claims 3-8, and 17 are canceled. Claim 20 is amended in the claim set of 3/23/2026 but without an updated status identifier. To advance compact prosecution, the status identifier is amended for claim 20. In the Response of 7/17/2026, claims 1, 14-16, 18-20, 22-23 and 25 are amended, claims 2 and 9-10 are canceled and new claim 27 is added.
Claims 1, 11-16, 18-25 and 27 are the claims under examination.
This Office Action contains new grounds for objection and rejection.
Priority
3. USAN 17/802,817, filed 08/26/2022, and having 1 RCE-type filing therein, is a National Stage entry of PCT/EP2021/ 055068, International Filing Date: 03/01/2021, claims foreign priority to EP 20159913.1, filed 02/27/2020, claims foreign priority to EP 20206317.8, filed 11/06/2020.
Information Disclosure Statement
4. As of 10/13/2026, a total of three (3) IDS are filed: 8/26/2025; 3/11/2026; and 4/14/2026. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal of Objections
Specification
5. The objections to the disclosure because of informalities are withdrawn. Both clean and marked-up copies of the specification are filed.
a) The specification is amended to delete the two (2) instances of an embedded hyperlink and/or other form of browser-executable code.
b) The specification is amended to rectify the improper use of the term, i.e., BiaCore, Sulfolink, and nanobodies, which is a trade name or a mark used in commerce.
Claim Objections
6. The objection to Claims 1-2, 9-16, 18-25 because of informalities is moot for the canceled claims and withdrawn for the pending claims.
a) Claims 1, 11-16, and 18-25 are amended to recite “or anti-adrenomedullin antibody fragment” for consistency.
b) Claim 9 is canceled.
c) Claim 23 is amended to include the term “or” between the penultimate and final species of the VH region and the VL region.
Rejections Maintained
Claim Rejections - 35 USC § 112(a)
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 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 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.
Written Description
7. The rejection of Claims 1, 11-16, 18-25 and 27 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 is moot for the canceled claims and maintained for the pending claims.
(A) Applicants allege it is fundamentally illogical to demand that a
specification provides a structural definition for the product of a product by process subject matter and that this is inconsistent with over 100 years of caselaw. That is, demanding structural support for product by process subject matter is antithetical to the entire premises of what a product by process claim is and what it was created for.
Response to Arguments
Under MPEP 2138.05 and Birmingham v. Randall, 171 F.2d 957, 80 USPQ 371, 372 (CCPA 1948) "To establish an actual reduction to practice of an invention directed to a method of making a product, it is not enough to show that the method was performed. "[S]uch an invention is not reduced to practice until it is established that the product made by the process is satisfactory, and [] this may require successful testing of the product."
Claim interpretation
The product obtained by the process comprised within the method of treatment is not simply the production of just any anti-ADM antibody that binds the ADM peptide of SEQ ID NO: 4 by the production steps for anyone of steps (a)-(e) recited in claims 1 and 27, but is required to possess the additional functional attributes recited in:
the body of Claims 1 and 27 (treatment of distributive shock in a human patient following administration within 8.4 hours after occurrence of shock);
Claim 14 (exhibits a binding affinity to ADM of at least 10-7 M by label-free surface plasmon resonance);
Claim 15 (exhibits a binding affinity to ADM exhibits a binding affinity to ADM of between 1 x 10-9 to 3 x 10-9 by label-free surface plasmon resonance);
Claim 18 (binds to the N-terminal end (aa 1) of ADM);
Claim 19 (is an ADM stabilizing antibody or fragment thereof that enhances the half-life for the half retention time of ADM in serum, blood, or plasma by at least 10 %); and
Claim 20 (blocks the bioactivity of ADM not more than 80 %, using a peptide fragment consisting of contiguous amino acids 22 to 52 of the human ADM sequence as a reference antagonist in CHO- K1 cells expressing human recombinant ADM receptor).
Notably, claim 21 references the treatment aspect of the method of claim 1 in reciting “wherein said method further comprises administering chemotherapy, vasopressors, biologics, antibiotics, or anti- viral compounds to said subject.”
The foregoing examples are evidentiary support that the preamble of claim 1 (method of treatment for shock) is limiting and essential to understand the structural and functional meaning of the claims. Further, the body of generic claims 1 and 27 relies on the preamble of generic claims 1 and 27, respectively, for antecedent basis, i.e., the body refers to the method of treating shock first introduced in the preamble. See MPEP 2111.02. Accordingly, while the product by process steps in claims 1 and 27 comprise any one of 5 processes (separated by “or” language within claims 1 and 27) for the antibody of the invention, the claims are unequivocally drawn to a method of treatment requiring the use of a genus of anti-ADM antibodies having selective functional properties well beyond “binding to the N-terminus of ADM of the sequence YRQSMNNFQGLRSFGCRFGTC (SEQ ID No. 4).”
“treatment”: the specification defines treatment falling within a therapy that includes observable outcomes, and not just binding to the sequence of SEQ ID NO: 4, at
[0327] Further preferred embodiments of the present invention relate to methods of therapy (e.g., treatment, curing, alleviating, improving, amelioration, etc.) or prevention of symptoms as defined in any of the foregoing embodiments comprising administering to a subject in need thereof the ADM antibody or an ADM antibody fragment or non-Ig-scaffold according to any of preceding embodiments. The subject is preferably a human.
(B) Applicants allege the decision from Teva is controlling case law for the instant claimed antibodies of the invention where “their only relevant function in this case is to bind to to the antigen (as defined specifically in the claim) and when one considers the claims as a whole, there is reasonable certainty that any antibody resulting from following the steps of the product by process claim will in fact bind to the N-terminus of ADM of the sequence YRQSMNNFQGLRSFGCRFGTC (SEQ ID No. 4).”
Response to Arguments
The lawsuit in Teva vs Lilly centered on competing migraine therapies by administering an effective amount of a humanized anti-CGRP antagonist antibody. Teva markets Ajovy® (fremanezumab), and Eli Lilly markets a competing antibody treatment called Emgality® (galcanezumab). Eli Lilly argued that Teva's patents were invalid under 35 U.S.C. § 112 for lack of written description and enablement, claiming Teva’s genus claims were too broad because the patent only explicitly disclosed a single humanized antibody species. Teva countered that the invention was a method of using a well-known genus to treat headaches, and used against Lilly, their own prior Patent Trial and Appeal Board (PTAB) statement where Lilly had argued that anti-CGRP antibodies and humanization were routine and well-known. Teva pointed to Lilly’s statements in the prior IPRs (and related appeals) regarding the obviousness of Teva’s “antibody patents”:
“[A]nti-CGRP antagonist antibodies were well known in the art”;
The “prior art” was “replete with exemplary disclosures of anti-CGRP antagonist antibodies, including humanized antibodies, to treat human diseases and conditions”;
“[A]nti-CGRP antagonist antibodies that bound to and blocked the biological effect of CGRP were well known in the art”; and
“[T]he prior art already reported several monoclonal anti-CGRP antagonist antibodies, including those that bound to and blocked human CGRP.”
As regards the instant application, the Office’s case-in-chief first presented in the Office Action of 9/23/2025 under section 9 for 112, 1st (written description) analysis provides evidentiary support substantiating the unpredictability of antibodies to even known antigen structures, but Applicants have yet to respond. There is no admission on the record that a genus of anti-ADM antibodies is routine and well-known much less for the use in treating “distributive shock” within “8.4 hours after occurrence of shock in said patient.”
See MPEP 2163 (II)(A)(3)(a) stating in part:
“…the claimed invention itself must be adequately described in the written disclosure and/or the drawings. For example, disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)(“knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011) (patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties).”
The structure/ function correlation is doctrinal under the written description requirements. If art is unpredictable and lacks a clear correlation showing that structural variations lead to predictable functional outcomes, relying broadly on functional language fails the written description requirement. The specification must show that the applicant was in possession of representative structures, not just the desired outcome.
(C) What is claimed vs what is shown in the specification?
Claim interpretation
“distributive shock”: the species of shock are proscribed by the definition provided in the specification at
[0033] The term “distributive shock” refers to a shock where the patient may have septic shock, neurogenic shock, anaphylactic shock or shock due to adrenal crisis. According to the cause, there are four types of distributive shock: neurogenic shock (decreased sympathetic stimulation leading to decreased vasal tone), anaphylactic shock, septic shock and shock due to adrenal crisis.
The specification fully discloses one anti-ADM antibody clone, Adrecizumab, in a method of treating septic shock in Example 2 at:
[0407] The AdrenOSS-2 trial was a double-blind, placebo-controlled, randomized, multicenter, proof-of-concept, biomarker-guided and dose-finding phase II trial to investigate the safety, tolerability, efficacy and pharmacokinetics of Adrecizumab in patients with early septic shock and elevated bio-ADM levels. The trial was conducted in thirty hospitals with medical, surgical and/or mixed ICU in Belgium, France, Germany and the Netherlands. Further details on the trial setting have already been reported earlier by Geven et al. (Geven C, Blet A, Kox M, Hartmann O, Scigalla P, Zimmermann J, Marx G, Laterre P F, Mebazaa A, Pickkers P, (2019) A double-blind, placebo-controlled, randomised, multicentre, proof-of-concept and dose-finding phase II clinical trial to investigate the safety, tolerability and efficacy of adrecizumab in patients with septic shock and elevated adrenomedullin concentration (AdrenOSS-2). BMJ Open 0: e024475).
“8.4 hours”: the specification fully discloses one anti-ADM antibody clone, Adrecizumab, in a method of treating septic shock with intervention within 8.4 hours after occurrence of the shock in Example 2 at:
[0426] To investigate the impact of the length of time between shock diagnosis and the start of treatment with Adrecizumab, the population was split in two groups at the median of the length of time between shock diagnosis and the start of treatment, namely 8.4 hours, and both groups were compared. The 28-day mortality rate was lower with Adrecizumab treatment compared to placebo when the treatment was administered between 0 and 10 hours after shock was diagnosed (HR 0.439 (0.174-1.11)) (FIG. 1A). When the time between shock diagnosis and treatment was between 10 and 12.2 hours the difference in mortality rate between Adrecizumab treatment compared to placebo was less pronounced (HR 0.711 (0.326-1.55)) (FIG. 1B).
[0427] FIG. 2 shows the changes in SOFA Score when Adrecizumab treatment was administered within 8.4 h after shock diagnosis (FIG. 2A) compared to treatment later than 8.4 h after shock diagnosis (FIG. 2B) supporting the surprisingly beneficial effect of the antibody of the present invention.
The POSA could reasonably conclude the method claims are not commensurate in scope with the written description disclosure in the specification as filed, namely, the use of just any anti-ADM antibody in treating any form of disruptive shock in a shock patient with intervention within 8.4 hours after occurrence of the shock. The rejection is maintained.
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.
8. The rejection of Claims 1, 11-16, 18-25 and 27 under 35 U.S.C. 103 as being unpatentable over Clinical Trial NCT03085758 (“A Double-Blind, Placebo-Controlled, Randomized, Multicenter, Proof of Concept and Dose-Finding Phase II Clinical Trial to Investigate the Safety, Tolerability and Efficacy of ADRECIZUMAB in Patients With Septic Shock and Elevated Adrenomedullin”; posted 2017-03-21; ‘758) is moot for the canceled claims and maintained for the pending claims.
(A) Applicants allege amending the claims to recite the patient suffers from “distributive shock” where the genus of anti-ADM antibodies is administered “within 8.4 hours after occurrence of the shock” overcomes the rejection.
Response to Arguments
The most generic claims 1 and 27 are not drawn to ADRECIZUMAB nor are they drawn to treating septic shock. The NCT reference teaches treating septic shock using ADRECIZUMAB.
The specification defines septic shock is a specific species of disruptive shock.
“distributive shock”: the species of shock are proscribed by the definition provided in the specification at
[0033] The term “distributive shock” refers to a shock where the patient may have septic shock, neurogenic shock, anaphylactic shock or shock due to adrenal crisis. According to the cause, there are four types of distributive shock: neurogenic shock (decreased sympathetic stimulation leading to decreased vasal tone), anaphylactic shock, septic shock and shock due to adrenal crisis.
The most generic claims 1 and 27 are not drawn to ADRECIZUMAB nor are they drawn to treating septic shock with intervention within 8.4 hours after occurrence of the shock.
“8.4 hours”: The NCT reference teaches treating septic shock using ADRECIZUMAB as a maximum of less than 12 hours between onset of the cardiovascular organ-dysfunction and administration of ADRECIZUMAB.
The specification fully discloses one anti-ADM antibody clone, Adrecizumab, in a method of treating septic shock with intervention within 8.4 hours after occurrence of the shock in Example 2 at:
[0426] To investigate the impact of the length of time between shock diagnosis and the start of treatment with Adrecizumab, the population was split in two groups at the median of the length of time between shock diagnosis and the start of treatment, namely 8.4 hours, and both groups were compared. The 28-day mortality rate was lower with Adrecizumab treatment compared to placebo when the treatment was administered between 0 and 10 hours after shock was diagnosed (HR 0.439 (0.174-1.11)) (FIG. 1A). When the time between shock diagnosis and treatment was between 10 and 12.2 hours the difference in mortality rate between Adrecizumab treatment compared to placebo was less pronounced (HR 0.711 (0.326-1.55)) (FIG. 1B).
[0427] FIG. 2 shows the changes in SOFA Score when Adrecizumab treatment was administered within 8.4 h after shock diagnosis (FIG. 2A) compared to treatment later than 8.4 h after shock diagnosis (FIG. 2B) supporting the surprisingly beneficial effect of the antibody of the present invention.
Thus, the NCT reference falls squarely within the breadth of scope for the instant claims. Under MPEP 2144.05 In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960) (MPEP 716.02(d)).
(B) Applicants allege the claims explicitly recite, "administering an anti-adrenomedullin (ADM) antibody or an anti-adrenomedullin antibody fragment that binds to the N-terminus of ADM of the sequence YRQSMNNFQGLRSFGCRFGTC (SEQ ID No. 4)." That is, the claims explicitly require that which conveys the unexpected results and this the claims are perfectly commensurate in scope with the showing of unexpected results.
Response to Arguments
Applicants rely on Attorney arguments that are not substantiated by extrinsic evidence showing that in vivo use of any anti-ADM antibody binding to the sequence of SEQ ID NO: 4 will yield unexpected results in a method of treatment. MPEP 716.01 and 2145 (The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)).
The specification fully discloses one anti-ADM antibody clone, Adrecizumab, in a method of treating septic shock with intervention within 8.4 hours after occurrence of the shock is what yields unexpected results in Example 2 at:
[0426] To investigate the impact of the length of time between shock diagnosis and the start of treatment with Adrecizumab, the population was split in two groups at the median of the length of time between shock diagnosis and the start of treatment, namely 8.4 hours, and both groups were compared. The 28-day mortality rate was lower with Adrecizumab treatment compared to placebo when the treatment was administered between 0 and 10 hours after shock was diagnosed (HR 0.439 (0.174-1.11)) (FIG. 1A). When the time between shock diagnosis and treatment was between 10 and 12.2 hours the difference in mortality rate between Adrecizumab treatment compared to placebo was less pronounced (HR 0.711 (0.326-1.55)) (FIG. 1B).
[0427] FIG. 2 shows the changes in SOFA Score when Adrecizumab treatment was administered within 8.4 h after shock diagnosis (FIG. 2A) compared to treatment later than 8.4 h after shock diagnosis (FIG. 2B) supporting the surprisingly beneficial effect of the antibody of the present invention.
The rejection is maintained.
9. The rejection of Claims 1, 11-16, 18-25 and 27 under 35 U.S.C. 103 as being unpatentable over Clinical Trial NCT03989531 (“Adrecizumab in Cardiogenic Shock (ACCOST-HH); posted 2019-06-18; ‘531) is moot for the canceled claims and maintained for the pending claims.
Applicants singular reply is indistinguishable as between NCT 758 above and NCT 531 herein. For purposes of brevity and compact prosecution, the prosecution from section 8 is incorporated in full herein.
The rejection is maintained.
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.
10. The provisional rejection of Claims 1, 11-16, 18-25 and 27 on the ground of nonstatutory double patenting as being unpatentable over claims 1,3-4, 6, 10, 18-19, 22-26, 28 and 36 of copending Application No. 17/801,108 (reference US 20230104578) is moot for the canceled claims and maintained for the pending claims.
Applicants comment that “unexpected results demonstrated by the claims of the current application and discussed above are sufficient to render all of the double patenting rejections moot” is indecipherable. The breadth and scope of the claimed invention, not the claims per se, have not been demonstrated by intrinsic nor extrinsic evidence to substantiate unexpected results for the universe of anti-ADM antibodies that meet the structure/ function requirements.
The rejection is maintained.
11. The provisional rejection of Claims 1, 11-16, 18-25 and 27 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, 24, 26-29, and 33 of copending Application No. 17/802,799 (reference application no. 20230193348) is moot for the canceled claims and maintained for the pending claims.
Applicants comment that “unexpected results demonstrated by the claims of the current application and discussed above are sufficient to render all of the double patenting rejections moot” is indecipherable. The breadth and scope of the claimed invention, not the claims per se, have not been demonstrated by intrinsic nor extrinsic evidence to substantiate unexpected results for the universe of anti-ADM antibodies that meet the structure/ function requirements.
The rejection is maintained.
12. The provisional rejection of Claims 1, 11-16, 18-25 and 27 on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8, 14-15, and 20-27, of copending Application No. 19/099,348 (US 20260167706) is moot for the canceled claims and maintained for the pending claims.
Applicants comment that “unexpected results demonstrated by the claims of the current application and discussed above are sufficient to render all of the double patenting rejections moot” is indecipherable. The breadth and scope of the claimed invention, not the claims per se, have not been demonstrated by intrinsic nor extrinsic evidence to substantiate unexpected results for the universe of anti-ADM antibodies that meet the structure/ function requirements.
The rejection is maintained.
13. The provisional rejection of Claims 1, 11-16, 18-25 and 27 on the ground of nonstatutory double patenting as being unpatentable over the claims to the following family of cases that are drawn to identical VH/CDR1-3 and VLCDR1-3 as well as the HC/LC that comprise the Adrecizumab antibody is moot for the canceled claims and maintained for the pending claims.
Applicants comment that “unexpected results demonstrated by the claims of the current application and discussed above are sufficient to render all of the double patenting rejections moot” is indecipherable. The breadth and scope of the claimed invention, not the claims per se, have not been demonstrated by intrinsic nor extrinsic evidence to substantiate unexpected results for the universe of anti-ADM antibodies that meet the structure/ function requirements.
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The rejection is maintained.
Objections Maintained
Specification
14. The objection to the disclosure because of informalities is maintained. The specification contains the peptide sequence “Ala-Ala-Ala-Ala” that is > 4 amino acids in length and required to be identified by sequence identifier (SEQ ID NO) pursuant to 37 CFR 1.821-1.825. The sequence listing containing new SEQ ID NO. 26 is not entered. See the new grounds for objection set forth below.
The objections are maintained.
New Grounds for Objection
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
New Grounds for Objection
Claim Objections
16. Claims 1, 11-16, 18-25 and 27 are objected to because of the following informalities:
a) Amend claim 1 to include numeration between the different product by process methods distinguished by “or” language in claim 1 for clarification:
Claim 1: A method of treatment for shock, comprising: administering an anti-adrenomedullin (ADM) antibody or an anti-adrenomedullin antibody fragment thereof that binds to the N-terminus of ADM of the sequence YRQSMNNFQGLRSFGCRFGTC (SEQ ID No. 4) to a patient with distributive shock who is a human, within 8.4 hours after occurrence of shock in said patient;
wherein said anti-adrenomedullin (ADM) antibody or an anti-adrenomedullin antibody fragment thereof is obtained as a product of the following process:
(a) injecting an animal with a peptide comprising amino acids 1-21 of ADM or a conjugate comprising a peptide comprising amino acids 1-21 of ADM,
fusing activated B-cells from the animal after injection with a myeloma cell line and culturing the resulting cells,
selecting and culturing cells expressing the anti-adrenomedullin (ADM) antibody or an anti- adrenomedullin antibody fragment thereof ; or
(b) injecting an animal with a peptide comprising amino acids 1-21 of ADM or a conjugate comprising a peptide comprising amino acids 1-21 of ADM,
fusing activated B-cells from the animal after injection with a myeloma cell line and culturing the resulting cells, and
selecting said cells expressing [the] a monoclonal antibody; or
(c) injecting an animal with a peptide comprising amino acids 1-21 of ADM or a conjugate comprising a peptide comprising amino acids 1-21 of ADM,
fusing activated B-cells from the animal after injection with a hybridoma cell line to produce a trioma cell line and culturing the resulting cells, and
selecting said cells expressing [the] a monoclonal antibody; or
(d) injecting an animal with a peptide comprising amino acids 1-21 of ADM or a conjugate comprising a peptide comprising amino acids 1-21 of ADM,
infecting activated B-cells from the animal after injection and culturing the resulting cells, and
selecting the immortalized B-cells expressing the monoclonal antibody; or
(e) targeting a peptide comprising amino acids 1-21 of ADM or a conjugate comprising a peptide comprising amino acids 1-21 of ADM in a phage display; or
(f) selecting human monoclonal antibodies that bind to a target molecule using a human combinatorial monoclonal antibody library, wherein the target molecule is the N-terminus of ADM [:] of the sequence YRQSMNNFQGLRSFGCRFGTC (SEQ ID No. 4).”
b) Amend claim 27 to include numeration between the different product by process methods distinguished by “or” language in claim 27 for clarification:
“A method of treatment for shock, comprising: administering to a patient with distributive shock who is a human, within 8.4 hours after occurrence of shock in said patient, a product of the following process:
(a) injecting an animal with [an] a peptide comprising amino acids 1-21 of ADM or a conjugate comprising [an] a peptide comprising amino acids 1-21 of ADM,
fusing activated B-cells from the animal after injection with a myeloma cell line and culturing the resulting cells,
selecting and culturing cells expressing the anti-adrenomedullin (ADM) antibody or an anti- adrenomedullin antibody fragment ; or
(b) injecting an animal with [an] a peptide comprising amino acids 1-21 of ADM or a conjugate comprising a peptide comprising amino acids 1-21 of ADM,
fusing activated B-cells from the animal after injection with a myeloma cell line and culturing the resulting cells, and
selecting said cells expressing [the] a monoclonal antibody; or
(c) injecting an animal with a peptide comprising amino acids 1-21 of ADM or a conjugate comprising a peptide comprising amino acids 1-21 of ADM,
fusing activated B-cells from the animal after injection with a hybridoma cell line to produce a trioma cell line and culturing the resulting cells, and
selecting said cells expressing [the] a monoclonal antibody; or
(d) injecting an animal with a peptide comprising amino acids 1-21 of ADM or a conjugate comprising a peptide comprising amino acids 1-21 of ADM,
infecting activated B-cells from the animal after injection and culturing the resulting cells, and
selecting the immortalized B-cells expressing [the] a monoclonal antibody; or
(e) targeting a peptide comprising amino acids 1-21 of ADM or a conjugate comprising a peptide comprising amino acids 1-21 of ADM in a phage display; or
(f) selecting human monoclonal antibodies that bind to a target molecule using a human combinatorial monoclonal antibody library, wherein the target molecule is the N-terminus of ADM[:] of the sequence YRQSMNNFQGLRSFGCRFGTC (SEQ ID No. 4).”
c) Amend claims 1, 11-16, 18-25 and 27 to recite “or anti-adrenomedullin antibody fragment thereof.”
Appropriate correction is required.
New Grounds for Rejection
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
17. Claim 18 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 18 recites “wherein said anti- adrenomedullin (ADM) antibody or anti-adrenomedullin antibody fragment binds to the N-terminal end (aa 1) of ADM.” The N-terminal end of claim 18 is broader in scope than the N-terminal end of AMD comprising the sequence of SEQ ID NO: 4 in claim 1, and by which the antibodies of the method of treatment are selected for binding.
Applicants may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 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 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.
Written Description/ New Matter
18. Claim 11 is 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(s) 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.
Claim 11 recites the term “bioADM” that is not found in the specification or drawings of the original filed application. A general search in public databases for the terms <bioAMD and protein> does not identify any known compound or structure. ((MPEP 706.03(m) states in part "New matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP § 608.04 to § 608.04(c). See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976) and MPEP § 2163.05 for guidance in determining whether the addition of specific percentages or compounds after a broader original disclosure constitutes new matter.”)
Conclusion
19. No claims are allowed.
20. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
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