DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 26 January 2026 has been entered.
Applicant’s amendment filed 26 January 2026 has been received and entered. Claims 15 and 25 have been amended and claims 1-14, 16-24 and 26-34 have been canceled. Claims 15 and 25 are currently pending and under consideration in the instant Office action.
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or rejection of record which is not expressly repeated n this action has been overcome by Applicant’s response and withdrawn.
Applicant’s arguments filed 26 January 2026 have been fully considered but are not found to be persuasive.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The newly submitted title contains a misspelling (SURGIGAL) as well as not being clearly indicative of the invention to which the claims are directed (method administers an anti-interleukin-1α antibody which is a key aspect of the invention to which the claims are directed).
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 15 and 25 are 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 limitation “means for binding” invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. While the specification administered a monoclonal antibody identified as MABp1, the instant application fails to provide a written description/structure of this monoclonal antibody and only references this antibody by way of mention to another patent application, 13/225,029, in paragraph [0009] in the specification (it is noted that this material was not incorporated by reference). Lastly, 13/225,029 does not provide a limiting disclosure for MABp1 because the disclosure of 13/225,029 appears to reference two different antibodies named MABp1 and therefore, there is no basis for determining which MABp1 is intended by the instant disclosure or what structure would be possessed by an antibody named “MABp1”. The specification also states at [0022] that any suitable type of antibody or other biologic agent that specifically binds IL-1α and prevents or delays complications in a human subject having received or expected to receive surgical treatment for a stenosed blood vessel might be used in the invention, no such structures/antibodies/materials are disclosed. While the specification envisions anti-IL-1α antibodies as having particular association rate (Ka), the disclosure does not describe any antibodies which would possess such properties or for which the stated outcome of the claims is achieved. Therefore, the claims are indefinite and are rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
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 15 and 25 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.
The instant claims are directed to methods which require administration of “a neutralizing interleukin-1α (IL-1α) antibody” and wherein “the chance of a major adverse clinical event occurring in the subject is reduced by at least 50% 15 weeks after the initial administration of the pharmaceutical composition”. The only compound which is provided in the instant specification is a monoclonal antibody identified as MABp1. However, the instant application fails to provide a written description of this monoclonal antibody and only references this antibody by way of mention to another patent application, 13/225,029, in paragraph [0009] in the specification. It is noted that this material was not incorporated by reference. Lastly, 13/225,029 does not provide a limiting disclosure for MABp1 because the disclosure of 13/225,029 appears to reference two different antibodies named MABp1 and therefore, there is no basis for determining which MABp1 is intended or what structure would be possessed by “MABp1”. As there is no structure provided for MABp1, there is no written description for MABp1, which is the only compound disclosed in the instant specification as a means for neutralizing IL-1α and which results in the particular outcome recited in the claims. The subject matter of MABp1 is not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The specification at [0022] states that any suitable type of antibody or other biologic agent that specifically binds IL-1α and prevents or delays complications in a human subject having received or expected to receive surgical treatment for a stenosed blood vessel might be used in the invention. While the disclosure envisions anti-IL-1α antibodies as having particular association rate (Ka), the disclosure does not describe a genus of antibodies which would possess such properties or for which the stated outcome of the claims is achieved. In fact, the only antibody which is mentioned is MABp1, which is discussed above with regard to written description. The specification fails to provide an adequate written description for MABp1 and further, fails to support an adequate written description for a genus of antibodies for practicing the method of the instant claims.
While the prior art recognizes that the 6CDRs of an antibody are the portion of the antibody that primarily define the binding region of a given antibody, the instant claims do not recite any structural element for the monoclonal antibodies which bind IL-1α. A disclosure of a single species of antibody which possesses a particular association rate is not sufficient to the support the broad genus of any and all antibodies which possess that same property. In the instant disclosure, the structure of the MABp1 antibody is not provided and the specification does not teach or describe what structures would be necessary for an antibody to bind IL-1α with a Ka of at least 1x109M-1 (disclosed for MABp1).
The structures of the antibodies/antigen-binding fragments claimed are not adequately described. In AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., Ill USPQ2d 1780 (Fed. Cir. 2014) AbbVie had claims to functionally claimed antibodies and Centocor presented evidence that the antibodies described in AbbVie's patents were not representative of other members of the functionally claimed genus. The decision states, “When a patent claims a genus using functional language to define a desired result, ‘the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus.’ Id. at 1349. We have held that 'a sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can “visualize or recognize” the members of the genus.’ Id. at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). Here, the claimed invention is a class of fully human antibodies that are defined by their high affinity and neutralizing activity to human IL-12, a known antigen. AbbVie's expert conceded that the '128 and '485 patents do not disclose structural features common to the members of the claimed genus.”
The AbbVie decision considers how large of a genus is involved and what species of the genus are described in the patent. With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus. See Ariad, 598 F.3d at 1353 (The written description requirement guards against claims that “merely recite a description of the problem to be solved while claiming all solutions to it and ... cover any compound later actually invented and determined to fall within the claim's functional boundaries.”).
In the instant application, the specification and claims draw a fence around a perceived genus but the genus is not adequately described. While the specification discloses a method which utilized an IL-1α antibody (named MABp1), this singular antibody (for which no structure is provided) does not support a genus of neutralizing interleukin-1α antibodies. No reasonable structure-function correlation has been established that is commensurate in scope with the claims with regard to the broad genus of neutralizing agents as no structure is provide at all. The specification does not describe representative examples to support the full scope of the claims.
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). 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.”
Thus, 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 genera of antibodies recited in the claims. "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. 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 of antibodies which provide a means for neutralizing IL-1α. 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 refers to pages 35-36 of Ex parte Chamberlain (Appeal 2022-001944) and asserts that the Appeals Review Panel found that claim 9 of U.S. Pat. Application no. 16/803,690 complied with the written description requirement and that the current claims are drafted in a similar manner. Applicant’s argument has been fully considered, but is not found persuasive. The decision that Applicant has cited (mailed 10 January 2023 – this is the only decision of Appeal 2022-001944 which has 36 pages or more) made a new ground of rejection for claim 9 for lack of written description and that rejection/decision was reheard and the rejection/decision was affirmed on 01 June 2023. The Examiner cannot find at any point in the prosecution history of the cited application that claim 9 was found to have written description by the Appeals Review Panel, contrary to Applicant’s assertion.
Applicant, at “B.” on page 2 of the response, asserts that “the amendments to claims 15 and 25 presented herein are believed to render this rejection moot for the reasons provided in the foregoing section”. Applicant’s response has been considered, but is not found persuasive for the reasons provided above in the grounds of rejection.
Claims 15 and 25 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The instant claims are directed to a method of reducing the chance of a major adverse clinical event or reducing the chance of restenosis, both occurring in a human subject having received or expected to receive surgical treatment for a stenosed blood vessel, the method comprising “the step of administering to the subject a neutralizing anti-interleukin-1α (IL-1α) antibody which comprises a means for binding and neutralizing interleukin-1α (IL-1α) and a constant region” and wherein a particular outcome is achieved by the administration.
The instant specification at page 9 lists Example 1 as “CV-18C3 is a sterile injectable liquid formulation of MABp1 in a stabilizing isotonic buffer”. Example 2 administered MABp1 to patients intravenously (3.75 mg/kg at day 0 and weeks 2, 4 and 6) followed subcutaneous administration (200 mg every 4 weeks starting at month 2) wherein the patients undergoing percutaneous femoro-popliteal revascularization. The results achieved by this administration regimen resulted in a reduction in the chance of a major adverse clinical event and chance of restenosis by at least 50% 15 weeks after the initial administration of the liquid formulation of MABp1.
The claims fail to comply with the enablement requirement because the claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. Example 2, described in the specification and discussed above does in fact achieve the stated results of claims 15 and 25, however, one or ordinary skill in the art would not be able to make/use the invention because specification does not provide an enabling disclosure for the antibody being used in the method (MABp1). The specification does not provide an adequate written description of the antibody named MABp1. The antibody (MABp1) does not appear to have been publicly available before the effective filing date of the claimed invention and the sterile injectable liquid formulation mentioned in Example 1 (CV-18C3) also does not appear to have been publicly available before the effective filing date of the claimed invention.
The only working embodiment disclosed in the instant administered the antibody MABp1. This embodiment is not enabled because the antibody is not described and therefore, the skilled artisan cannot practice this method as the antibody was not available and not adequately described. With regard to the claimed methods recited in claims 15 and 25, the instant specification does not provide an enabling disclosure for the scope of the claims because the only means for neutralizing interleukin-1α which is disclosed is MABp1, but it is only disclosed by name and no distinguishing properties of MABp1 are provided.
The instant specification discloses a single working embodiment of treatment which provides the necessary results of a reduction of the chance of major adverse clinical event or restenosis by at least 50% 15 weeks after the initial administration of the pharmaceutical composition in the subjects having received or expected to receive surgical treatment for a stenosed blood vessel. The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable arts, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971). However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938).
The courts have stated that the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Chamberlain (Am. J. Pathol. 168: 1396-1403, 2006) and Patti (Am. J. Cardiol. 89: 372-376, 2002) (cited by Applicant) demonstrate that before the effective filing date of the claimed invention, one of ordinary skill in the art would have found the state of the art to be unpredictable because IL-1α was not known to play a causative role in neointima formation. Chamberlain showed that, after vessel injury, IL1β knockout mice exhibited reduced neointima formation compared to control, while IL-1α knockout mice exhibited the same amount of neointima formation as the control group. Patti showed that patients with high IL-1ra (receptor inhibitor) plasma levels were at a higher risk of developing MACE after percutaneous coronary intervention for coronary artery disease. As these references teach away from inhibiting IL-1α in order to inhibit neointima formation, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it unpredictable to administer an IL-1α antibody, let alone any “means for neutralizing IL-1α” to reduce the chance of MACE or restenosis in a subject receiving or expected to receive surgical treatment for a stenosed blood vessel. Furthermore, as the state of the prior art at the time of the invention would have found it unpredictable to inhibit IL-1α for any benefit of inhibiting neointima formation, it cannot provide any guidance or direction with regard to the claimed methods.
The instant specification teaches a single example of treatment which resulted in the claimed of effect of reducing the chance of a major adverse clinical event or restenosis by at least 50% 15 weeks after the initial administration of the pharmaceutical composition. The only treatment regimen which was used administered MABp1 at a dose of 3.75 mg/kg at day 0 and weeks 2, 4, 6 followed by subcutaneous administration at a dose of 200 mg every 4 weeks starting at month 2. There is no evidence of record which would support a conclusion that the specific antibody used could be administered at lower doses to achieve the desired and required result. There is no evidence of record which would support a conclusion that the specific antibody used could be administered at higher doses to achieve the desired and required result. In fact, because Patti showed that patients with high IL-1ra (receptor inhibitor) plasma levels were at a higher risk of developing MACE after percutaneous coronary intervention for coronary artery disease, one of ordinary skill in the art would reasonably expect that higher doses would increase the risk of developing MACE because an antibody which binds IL-1α would result in less receptor activation as is the case with increased IL-1ra. Furthermore, one of ordinary skill in the art would not expect that lower doses would achieve the desired and required outcome because normally physiological outcomes tend to be dose dependent. Likewise, one of ordinary skill in the art would not reasonably conclude that the specific dosing regimen which was used in Example 2 in the specification which resulted in the stated 50% reduction in chance of MACE or restenosis to be predictive of dosing regimens which differ in number of dosages, routes of administration and dosage amounts. There is no evidence provided which would suggest that the dosing regimen could be adjusted and result in the claimed result of the claims (reducing the chance of a major adverse clinical event or restenosis by at least 50% 15 weeks after the initial administration of the pharmaceutical composition) and because there are no other treatment regimens presented, there is no means to extrapolate to other regimens which would provide for the claimed outcome. The amount of experimentation required to achieve the desired/claimed results would be undue because of the number of variables which would impact the outcome (IV dosage, the number of IV doses given, the subcutaneous dosage, the number of sc doses given, the time between doses and the antibody/means which is administered). Furthermore, specification does not provide an enabling disclosure for MABp1. Because MABp1 was not available at the time the instant invention was made, there is no information regarding its structure and therefore no information with which to compare other IL-1α antibodies. IL-1α antibodies were known in the art at the time of the instant invention however there is no information regarding IL-1α antibodies neointima formation or restenosis. It is unknown if any IL-1α antibody could be used in the claimed method or if the antibody must bind to a particular epitope on IL-1α to be effective or if a particular binding affinity is required to be effective or if any other compound which neutralizes IL-1α would achieve the same results.
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability, 5) existence of working samples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). As pointed out above, the nature of the invention and the state of the prior art are known to be unpredictable as the prior art of record taught away from the claimed invention. While the skill in the art is high, this does not make up for the fact that the claims are extremely broad when considering the number of variables involved and the lack of direction/guidance in the specification because of the singular example provided in the specification. Lastly, the only working example in the specification utilizes an antibody for which there is no written description, therefore, the MABp1 antibody is also not enabled because one of ordinary skill in the art would not be able to make it. Taking into account all of these factors, it would require undue experimentation to practice the invention as claimed in order to reduce a major adverse clinical event or restenosis in a subject having received or expected to receive surgical treatment for a stenosed blood vessel by at least 50% 15 weeks after the initial administration of the pharmaceutical composition.
Response to Arguments
Applicant argues at pages 2-3 of the response that the Examiner’s conclusion that MABp1 was not available at the time of the instant invention and that there is no information regarding its structure is incorrect. Applicant asserts that paragraph 9 of the instant application indicates that MABp1 is described in US Pat. application 13/225,029 and was published on 01/19/12 and alleges that the amino acid sequences of the heavy and light chain of MABp1 are those of SEQ ID NO:9 and 11, respectively.
Applicant’s argument has been fully considered, but is not found persuasive. As pointed out in the written description rejection above (and in the previous Office action, mailed 27 October 2025). The instant application only references this antibody by way of mention to another patent application, 13/225,029, in paragraph [0009] in the specification (and the material was not incorporated by reference). The disclosure of 13/225,029 (U.S. Pat. No. 8,962,814) does not provide a limiting disclosure for MABp1 because the disclosure of 13/225,029 appears to reference two different antibodies named MABp1 and therefore, there is no basis for determining which MABp1 is intended or what structure would be possessed by “MABp1”.
‘814 mentions “MABp1” in Example 4 (column 14 at line 45 and 56). ‘814 then states in Example 5, lines 62-64, the “complete sequence encoding for another human anti-hIL-1algG1/Kappa light chain specific for human IL1α (MABp1) was synthesized and expressed as described above.” Based on the two distinct recitations of MABp1 and the statement regarding “another” MABp1, the skilled artisan is not apprised of which MABp1 is intended or which properties/characteristics are associated with which “MABp1” as there are clearly more than one disclosed in 13/225,029.
As there is no structure provided for MABp1, there is no written description for MABp1, which is the only compound disclosed in the instant specification as a means for neutralizing IL-1α and which results in the particular outcome recited in the claims. The instant specification does not provide any distinguishing information for how to make an antibody which would neutralize IL-1α such as epitope to be bound and have the necessary functionality of reducing the chance of a major adverse clinical event in a subject by at least 50% 15 weeks after the initial administration, contrary to Applicant’s assertion.
Applicant cites MPEP 2164.0 at pages 3-4 of the response and asserts that the claims are fully enabled because the “how to make” part of the enablement requirement is satisfied if the specification discloses at least one method for making and using the claimed invention that bears a reasonable correlation to the entire scope of the claim. Applicant’s argument has been fully considered, but is not found persuasive. As pointed out previous, the nature of the neutralizing anti-IL-1α is unknown. Additionally, the specification teaches a single example of treatment which resulted in the claimed of effect of reducing the chance of a major adverse clinical event or restenosis by at least 50% 15 weeks after the initial administration of the pharmaceutical composition. The only treatment regimen which was used administered MABp1 at a dose of 3.75 mg/kg at day 0 and weeks 2, 4, 6 followed by subcutaneous administration at a dose of 200 mg every 4 weeks starting at month 2. There is no evidence of record which would support a conclusion that the specific antibody used could be administered at lower doses to achieve the desired and required result. There is no evidence of record which would support a conclusion that the specific antibody used could be administered at higher doses to achieve the desired and required result. In fact, because Patti showed that patients with high IL-1ra (receptor inhibitor) plasma levels were at a higher risk of developing MACE after percutaneous coronary intervention for coronary artery disease, one of ordinary skill in the art would reasonably expect that higher doses would increase the risk of developing MACE because an antibody which binds IL-1α would result in less receptor activation as is the case with increased IL-1ra. Furthermore, one of ordinary skill in the art would not expect that lower doses would achieve the desired and required outcome because normally physiological outcomes tend to be dose dependent. Likewise, one of ordinary skill in the art would not reasonably conclude that the specific dosing regimen which was used in Example 2 in the specification which resulted in the stated 50% reduction in chance of MACE or restenosis to be predictive of dosing regimens which differ in number of dosages, routes of administration and dosage amounts. There is no evidence provided which would suggest that the dosing regimen could be adjusted and result in the claimed result of the claims (reducing the chance of a major adverse clinical event or restenosis by at least 50% 15 weeks after the initial administration of the pharmaceutical composition) and because there are no other treatment regimens presented, there is no means to extrapolate to other regimens which would provide for the claimed outcome. The amount of experimentation required to achieve the desired/claimed results would be undue because of the number of variables which would impact the outcome (IV dosage, the number of IV doses given, the subcutaneous dosage, the number of sc doses given, the time between doses and the antibody/means which is administered). Furthermore, specification does not provide an enabling disclosure for MABp1. Because MABp1 was not available at the time the instant invention was made, there is no information regarding its structure and therefore no information with which to compare other IL-1α antibodies. IL-1α antibodies were known in the art at the time of the instant invention however there is no information regarding IL-1α antibodies neointima formation or restenosis. It is unknown if any IL-1α antibody could be used in the claimed method or if the antibody must bind to a particular epitope on IL-1α to be effective or if a particular binding affinity is required to be effective or if any other compound which neutralizes IL-1α would achieve the same results. Therefore, the disclosure of the instant specification fails to provide a reasonable correlation to the entire scope of the claims, contrary to Applicant’s assertion.
Applicant argues at page 6 of the response that the invention was the first to disclose that administration of a neutralizing antibody to IL-1α could reduce the change of a major adverse clinical event (MACE) or restenosis occurring in a human and that prior to this discovery, it was unknown what effects, if any, administration of a neutralizing antibody to IL-1α would have on MACE. Applicant then asserts that the examiner’s reasoning why a single working embodiment with a specific dosage, a specific dosing regimen and a singular antibody which is not described structurally is not commensurate in scope with the claims to a method that lacks any specificity to dose, regimen or compound to be administered is not consistent with In re Goffe. While it is appreciated that Applicant would like breadth in what is claimed, a singular species rarely supports a broad genus. The Examiner has provided a detailed analysis as to why the instant claims are not enabled (see above) and Applicant has not argued the merits of the rejection and has attempted to merely rely on case law which is not persuasive.
Claims 15 and 25 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 15 and 25 have been amended to recite administering “a neutralizing anti-interleukin-1α(IL-1α) antibody which comprises a means for binding and neutralizing interleukin-1α(IL-1α) and a constant region”. This limitation is new matter. The specification as originally filed does not include the term “means” nor does it include the term “neutralizing”. The specification at [0022] states that any suitable type of antibody or other biologic agent that specifically binds IL-1α and prevents or delays complications in a human subject having received or expected to receive surgical treatment for a stenosed blood vessel might be used in the invention. However, this disclosure does not provide basis for the limitation of “neutralizing anti-interleukin-1α (IL-1α) antibody”. Therefore, the claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor/joint inventor/inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Response to Arguments
Applicant asserts at page 7 of the response that the rejection is moot in view of the amendment to the claims. Applicant states that before the priority date of the current application, the MABp1 antibody was “well known to neutralize IL-1α (pointing to paragraph 54 of the ‘384 publication). Applicant’s argument has been fully considered, but is not found persuasive. The instant specification must provide basis for the limitations of the instant claims. The instant specification at no point utilizes the term “means” nor does it utilize the term “neutralizing”. The specification at [0022] states that any suitable type of antibody or other biologic agent that specifically binds IL-1α and prevents or delays complications in a human subject having received or expected to receive surgical treatment for a stenosed blood vessel might be used in the invention. However, this disclosure does not provide basis for the limitation of “neutralizing anti-interleukin-1α (IL-1α) antibody”. The instant claims are not directed to a method which administers MABp1 of the ‘384 publication nor is there basis to limit the instant claims to an antibody that is neutralizing for IL-1α as currently claimed, therefore, the claims contain new matter.
Conclusion
No claim is allowed.
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/Christine J Saoud/Primary Examiner, Art Unit 1645
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