DETAILED ACTION
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after appeal to the Patent Trial and Appeal Board, but prior to a decision on the appeal. 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examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 25 June 2025 has been entered.
Applicant’s responses filed 25 June 2025 and 08 October 2025 have been received and entered. Claims 21 and 28 have been amended and claims 1-20, 22-23, 25-27 and 29 have been previously canceled.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Any objection or rejection of record which is not expressly repeated in this action has been overcome by Applicant’s response and withdrawn.
Applicant’s arguments filed 08 October 2025 have been fully considered but are not found to be persuasive.
Drawings
The drawings were received on 25 June 2025. These drawings are not acceptable.
Figure 1 –
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The text is not solid black. It is fuzzy and hard to read.
Figure 2 –
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The text is of such poor quality, the text is not legible.
Figure 3 – the lines of the drawing are not solid black.
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37 CFR 1.84(a)(1) requires the use of India ink, or its equivalent that secures solid black lines. Additionally, 37 CFR 1.84(l) requires that all drawings must be made by a process which will give them satisfactory reproduction characteristics and that every “line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined”.
As can be seen by the screenshot provided above, the lines are not black, sufficiently dense and dark and not uniformly thick. This results in portions of the drawings being faint and blurry. Correction is required.
Specification
Applicant’s submission of a substitute specification to correct deficiencies noted with regard to Sequence Compliance has been received and entered. The instant application is now in compliance with the Sequence rules.
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because it is not a single paragraph and it is not reflective of that which is new in the art to which the invention pertains (the invention is that which is defined by the claims). Correction is required. See MPEP § 608.01(b).
Applicant did not appear to address this objection in the most recent response. Therefore, the objection is maintained for the reasons of record.
Response to Arguments
The previous ground of rejection made under 35 USC § 101 is withdrawn. Applicant asserts at page 12 of the response that the 101 rejection was the only asserted rejection against claim 28. Applicant is mistaken. In the final rejection, mailed 06 December 2024, claim 28 was rejected under 35 USC § 112(a).
Claim Rejections - 35 USC § 112
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.
Claims 21, 24, 28, 30-43 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(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.
Claims 21 and 28 are directed to a composition comprising a complex comprising “at least one anti-mature ADM antibody or an antigen binding fragment thereof” and mature ADM in a sample of bodily fluid wherein said anti-mature ADM antibody or the antigen binding fragment thereof is “obtained by a process” wherein the process includes generation of an antibody by immunizing a mammal with mature ADM or screening for scFV against adrenomedullin from an antibody gene library. Claim 28 includes the addition limitation of “wherein said at least one anti-mature ADM antibody or the antigen binding fragment thereof exhibits a binding affinity to mature ADM of at least 107 M-1”.
The instant specification fails to provide an adequate written description for a antibodies/antigen binding fragments which bind mature ADM obtained by the recited processes as well as failing to describe antibodies/fragments with the recited binding affinity of claim 28. Neither claim 21 nor claim 28 provide any structure what so ever for the anti-mature ADM antibody/antigen binding fragment in the claimed compositions. While the art before the effective filing date of the claimed invention teaches some antibodies which bind mature adrenomedullin, including mature ADM of SEQ ID NO:4, this does not appear to rise to the level of a recitation of a representative number of species falling within the scope of the genus and neither the prior art nor the instant specification provides any structure/function correlation with regard to antibody structure and binding affinity. The instant claims appear to be directed to a composition of any antibody which could be produced or identified in a screening procedure complexed to mature ADM from a bodily sample of any individual who is not suffering from shock and suffering from one of the recited conditions in the claims if the amount of mature adrenomedullin is above 70 pg/ml; thus encompassing any measurement of mature ADM in a clinical setting if the level of mature adrenomedullin is above 70 pg/ml.
Vas-Cath Inc. V. Mahurkar, 19 USPQ2d 1111, states that Applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention, for purposes of the written description inquiry, is whatever is now claimed (see page 1117). A review of the language of the claims indicates that claim 21 encompasses any anti-mature ADM antibody/antigen binding fragment that could be produced/isolated by the recited processes and claim 28 further requires the anti-mature ADM antibody/antigen binding fragment to exhibit a binding affinity to mature ADM of at least 107 M-1”. While the claims require an anti-mature ADM antibody/antigen binding fragment in the claimed composition which is obtained from a method/screen of a library, no actual antibodies/antigen binding fragments are described in the specification by any particular structure.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B(1), the court states, “An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.”
The specification at page 8 states that a binder with a particular binding affinity to proADM and/or fragments is desired and identifies methods to determine binding affinity of antibodies to adrenomedullin, there is no disclosure of a structure/function relationship with regard to binding affinity. The specification, beginning at page 20, discloses various methods for producing an antibody which would bind adrenomedullin, as well as means of screening antibody gene libraries. However, the specification provides no teachings as to which structural features of the claimed molecules would provide for binding to mature adrenomedullin or correlate with the property of the recited binding affinity of claim 28. In fact, the specification fails to teach any antibodies/fragments by structure and it is not clear which antibodies were utilized in the claimed methods as the specification only discloses that “antibodies were produced via standard antibody production methods” (see page 25).
Given the level of skill and knowledge and predictability in the art, those of skill in the art would not conclude that the applicant was in possession of the claimed genera of antibodies/fragments based on disclosures set forth above. The specification and the claims do not provide any guidance on the structure of the antibodies/fragments that must be present in order for the required binding specificity to be achieved (claim 28).
"A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly.
Further, it is not sufficient to define the genus solely by its principal biological property, because an alleged conception having no more specificity than that is simply a wish to know the identity of any material with that biological property. Per the Enzo court's example, (Enzo Biochem, Inc. v. Gen-Probe Inc., 63 USPQ2d 1609 (CA FC 2002) at 1616) of a description of an anti-inflammatory steroid, i.e., a steroid (a generic structural term) couched "in terms of its function of lessening inflammation of tissues" which, the court stated, "fails to distinguish any steroid from others having the same activity or function" and the expression "an antibiotic penicillin" fails to distinguish a particular penicillin molecule from others possessing the same activity and which therefore, fails to satisfy the written description requirement. Similarly, the function of the variant as claimed does not distinguish a particular variant from others having the same activity or function and as such, fails to satisfy the written-description requirement. Applicant has not disclosed any relevant, identifying characteristics, such as structure or other physical and/or chemical properties, sufficient to show possession of the claimed genus. Mere idea or function is insufficient for written description; isolation and characterization at a minimum are required. A description of what a material does, rather than what it is, usually does not suffice. (Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406).
In the absence of sufficient recitation of distinguishing characteristics, the specification does not provide adequate written description of the claimed genus, which are anti-mature ADM antibodies or antigen binding fragments thereof (claim 21) or which exhibit a binding affinity to mature ADM of at least 107 M-1 (claim 28). Further, the specification does not provide an adequate written description of any antibodies/fragments by structure. One of skill in the art would not recognize from the disclosure that the applicant was in possession of the genus. The specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed (see Vas-Cath at page 1116).
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 1115).
Response to Arguments
Applicant did not argue the written description rejection in the response filed 08 October 2025 or 25 June 2025. In the response filed 03 April 2025, Applicant argues at page 7 of the response that MPEP § 2163(II)(A)(3)(a)(i) “specifically addresses this situation and states unequivocally that applicants have satisfied written description”. The arguments in the response filed 14 April 2025 and 25 April 2025 appear to be identical to those of 03 April 2025.
Applicant’s argument has been fully considered, but is not found persuasive. MPEP § 2163(II)(A)(3)(a)(i) is directed to “claim drawn to a single embodiment or species”. The instant claims encompass a genus of antibodies/fragments. Furthermore, the methods which are recited do not result in the specified antibody/fragment as the processes result in a host of molecules which then must be screened for their ability to bind the specified target as well as be tested for their binding affinity. Therefore, the recitation of the processes in the instant claims do not actually appear to produce a specific species/product but rather a genus of compounds which then would require further screening and selection to arrive at a potential compound which could be used in the claimed sample. The MPEP at the section cited by Applicant goes on to state that “the requirement may not be satisfied where it is not clear that the acts set forth in the specification can be performed, or that the product is produced by that process”.
Applicant asserts at page 7 of the response that the rejection to claim 30 is moot in view of the amendment to the claims. Applicant’s argument has been fully considered, but is not found persuasive. It is not clear how claim 30, which recites that the mature ADM is measured with a sandwich assay avoids the rejection of record.
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.
Claim 24 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 24 is indefinite for the recitation of “a second binder that binds to a region comprised within the sequence of mature ADM”. The claim is indefinite because it is not clear if the “second binder” is distinct from the “at least one binder” of claim 21. Because the second binder binds to the same region as the “at least one binder”, it seems that the claim may encompass the multiple quantities of the first binder. There does not seem to be any reason why the first and the second binder are not the same as the second binder does not require binding to the C-terminal glycine as the antibody binds to a region comprised “within” the sequence. Therefore, the metes and bounds of the claim are indefinite.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 21 and 33-43 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hirata et al. (J. Clin. Endocrinol. 81(4): 1449-1453, 1996).
Hirata et al. teach measurement of human adrenomedullin (amino acids 1-52; see page 1449, column 1, last sentence) in biological samples from subjects with sepsis (page 1449, column 2, last paragraph). Of the 12 subjects, cases 11 and 12 did not suffer from septic shock (see page 1450, column 1, line 6). Hirata et al. teach that
plasma samples were collected in EDTA-containing tubes and hAM was measured using radioimmunoassay (see page 1450, column 1, under “Measurement of plasma immunoreactive (ir)-hAM”). Figure 1, bottom panel reports the plasma ir-hAM (fmol/ml) for case 11, which is more than 70 pg/ml. Therefore, a composition comprising a binder and mature ADM from a subject not suffering from shock is disclosed. With regard to the claim limitations for the binder, these are product by process limitations and MPEP 2113 makes clear that product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. With regard to claim 43, Hirata et al. is silent to the amount of MR-proADM present in the sample from case 11. However, the instant specification at page 4 states that MR-proADM and bio-ADM are generated in a stoichiometric ration from the same precursor and therefore, their plasma levels are correlated to a certain extent. See also page 33 of the specification at the bottom in which MR-proADM is “proposed as a surrogate marker for mature ADM”. Therefore, while Hirata et al. is silent to these levels, the sample from case 11 would be expected to contain more than 0.7 nmol/L of MR-proADM, absent evidence to the contrary.
Response to Arguments
Applicant asserts that it is not reported/disclosed whether patient 11 or 12 develop septic shock in the later course. Applicant’s statement is noted, but seems immaterial. The claims recite that the sample comes from a subject not suffering from a physiological shock state. If patients 11 and 12 were reported as not suffering from septic shock (see page 1450, column 1, line 6), they meet the limitation of the claims even if they develop the condition later.
Applicant argues at page 9 of the response that the assay of Hirata et al. uses an antibody that cross-reacts with ADM-Gly. Applicant is apparently arguing that the values that Hirata is measuring is not mature ADM even though Applicant states “Hirata et al. describe sepsis patients with the claimed human ADM values”.
Applicant’s arguments have been fully considered, but are not found persuasive. Hirata et al. does not state that the antibody used in the assay cross-reacts with ADM-Gly. Rather, Hirata et al. states that the antibody had 100% cross-reactivity with intact hAM(1-52) which has the same amino acid sequence of SEQ ID NO:4 of the instant claims. Additionally, Hirata et al. confirmed the protein which was being detected by performing HPLC on the plasma extracts from one of the patients (see Figure 3). Therefore, Hirata et al. anticipate the instant claims.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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 Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 6am-2:30pm.
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/Christine J Saoud/Primary Examiner, Art Unit 1645