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 .
Election/Restrictions
Applicant's election with traverse of species 2 (antibody/antigen-binding portion thereof comprising CDRs with the amino acid sequences of SEQ ID NO:2, 4, 6, 8, 10 and 12) in the reply filed on 17 February 2026 is acknowledged. The traversal is on the ground(s) that species 1 and 2 are “functionally related antibodies for modulating immune response” and therefore, “it would not be a serious burden to search and examine Species 1 and 2 in the same application. This is not found persuasive because the two antibodies recited in the claims are not structurally related (see sequences and querie match information for each CDR of embodiments 1 and 2).
HCDR1 (17.6%) LCDR1 (9.4%)
NYWIN (1) RASQNIGTSIH(1)
GFSLTSNSIS(2) KSSQSLLYSENQENYLA(2)
HCDR2 (14.9%) LCDR2 (31.2%)
NIYPSDTYINHNQKFKD(1) YASESIS(1)
AIWSGGGTDYNSDLKS(2) WASTRQS(2)
HCDR3 (14.8%) LCDR3 (17.9%)
SAYANYFDY(1) QQSDSWPTLT(1)
RGGYPYYFDY(2) QQYYDTPLT(2)
The search for the two antibodies is not coextensive and would require a completely distinct and independent search of the CDRs for the second antibody (as well as heavy/light chain sequences). This constitutes a serious burden of search.
The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statement (IDS) submitted on 31 May 2023 has been considered by the examiner.
Certain citations were lined through on the IDS because they do not include the identifying information required by 37 CFR 1.84(b)(5). Specifically, a publication date is required (note: a mailing date is not necessarily a publication date) and an author. For documents which were obtained by a searching authority, the searching authority may be considered the author if none is specifically identified. The material which was submitted has been considered (as indicated by the initials next to the citations) but the citations have been lined through as they are not compliant with 37 CFR 1.84.
Drawings
The drawings are objected to because they are not compliant with 37 CFR 1.84(a)(1) because the drawings (Figures 1, 2A, 5-10, 12-18) do not have “solid black lines”. The result is that the drawings appear fuzzy and text appearing blurry. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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:
As pointed out in (1)(b)(iii) above, the file size must be recited in bytes. The instant specification at [002] states “with a file size of about 43,845 bytes”. This language is not acceptable. A data file has a precise size and the use of the term “about” is not accurate or permitted. The term “about” should be deleted from paragraph [002]. This will require the submission of a substitute specification.
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 current title contains no information which would be “clearly indicative of the invention to which the claims are directed”. The claims are directed to antibodies which bind to CD11b and compositions thereof. Appropriate correction is required.
Improper Markush
Claims 1-3 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of an antibody/antigen-binding portion thereof comprising (A) (i) a heavy chain variable region comprising CDR’s having the amino acid sequence SEQ ID NO: 1, 3, 5; or SEQ ID NO: 2, 4, 6, and
(ii) a light chain variable region comprising CDR’s having the amino acid sequence SEQ ID NO: 7, 9, 11; or SEQ ID NO: 8, 10, 12; or
(B) heavy/light chain variable regions with the amino acid sequences of SEQ ID NO:18-22/28-32,
is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the antibodies/antigen-binding portions which are recited in the claims do not share a single structural similarity as pointed out above in the response to the traversal of the species election requirement. The CDRs of the encompassed antibodies/portions are not structurally related as shown by the lack of amino acid percent identity between the sequences and the structural similarity which may be possessed in common (antibody structure) is not sufficient to provide for the common use (binding CD11b). The different collections of heavy chain/light chain and CDRs relate to specific antibodies which bind a specific target. The structures of these heavy/light chains and CDRs is not shared by the different alternatives and therefore, the recited species do not share a common structure which provides for a common function and therefore, are not proper species of one another.
Claims 4-16 are rejected for depending on a rejected claim as they do not correct the above noted deficiency.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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 1-2, 4-6 and 11-13 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 an antibody or antigen-binding portion thereof comprising (i) a heavy chain variable region with 3 CDRs having the amino acid sequences of SEQ ID NO:1, 3 and 5 OR the amino acid sequences of SEQ ID NO:2, 4 and 6 and (ii) a light chain variable region with 3 CDRs having the amino acid sequence of SEQ ID NO:7, 9 and 11 OR the amino acid sequences of SEQ ID NO:8, 10 and 12 according to claim 1. Claim 2 defines the antibody or antigen-binding portion thereof as comprising a heavy chain variable region comprising the amino acid sequence of one of SEQ ID NO:13-22 and a light chain variable region comprising the amino acid sequence of one of SEQ ID NO:23-32. Claims 4-6 and 11-13 are directed to compositions which comprise the antibody or antigen-binding portion thereof of claims 1-2.
However, the claims fail to provide an adequate written description for such antibodies and antigen-binding portions thereof because while the claims recite CDR structures for the antibodies or heavy/light chain variable regions, the claims encompass mixing and matching of CDRs and heavy/light chains from different antibodies.
The claims as currently presented do not require the antibody to have a full complement of CDRs from a particular recited antibody or have two variable domains (heavy and light chain) from a particular antibody. The elected species of antibody has CDRs with the amino acid sequences of SEQ ID NO: 2, 4, 6, 8, 10 and 12 and heavy/light chain variable regions with the amino acid sequences of SEQ ID NO:18-22/28-32. An antibody with these structures (all 6 recited CDRs or both heavy/light chains) of CDRs has written description. However, the instant specification does not describe antibodies which mix and match CDRs from different antibodies which also have the ability to bind their respective targets. The instant specification does not teach antibodies with less than a complete complement of CDRs from the same antibody as having the ability to bind their stated target. Additionally, the specification does not teach a genus of antibodies which bind to a particular target which mix and match the CDRs of the heavy and light chain or which mix and match the heavy and light chain of different isolated antibodies.
The specification fails to provide a written description of the claimed antibodies/antigen-binding portions thereof in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention. The instant specification fails to describe any antibodies which mix and match CDRs and/or heavy/light variable chains, and there is no direction provided in the instant specification as to how to use such antibodies which mix and match CDRs/heavy/light chain variable regions as is encompassed by the claims. While the specification contemplates mixing and matching heavy and light chains from different antibodies and mixing and matching CDRs from different antibodies, the specification does not make such antibodies or demonstrate that such constructs would bind their respective target and have the necessary functional activities which would be required to use the antibodies of the claims.
The structures of the antibodies 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. The specification exemplifies an antibody which has CDRs with the amino acid sequences of SEQ ID NO: 2, 4, 6, 8, 10 and 12 and heavy/light chain variable regions with the amino acid sequences of SEQ ID NO:18-22/28-32; however, the claims are not so limited and the structural variability of the claimed genus is large. No reasonable structure-function correlation has been established that is commensurate in scope with the claims. 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 claimed genera of antibodies/antigen-binding portions thereof based on disclosures set forth above. "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 antibodies which mix and match CDRs and/or heavy/light chain variable regions. 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).
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 1-16 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.
Claims 1-7 all recite “antibody” or “antigen-binding portion thereof”. However, the claims fail to indicate what antigen is to be bound by the antibody and therefore, the claim is indefinite. Dependent claims 8-16 do not correct the deficiency of claims 1-7 and therefore, they are also indefinite for the same reason.
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.
Claims 4-7 are 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. Claims 4-7 are directed to either a composition or a pharmaceutical composition wherein the composition comprises an antibody or antigen-binding portion of one of the preceding claims. However, the claims do not limit the subject matter of the preceding claims as the only component of the composition is the recited antibody/antigen-binding portion. This rejection could be avoided by the recitation of a second component in the composition (e.g. an excipient or carrier). Applicant 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.
Art Made of Record
WO 2022/147338 A1 (Monoclonal antibody against human MAC-1 and uses thereof)
Conclusion
No claim is allowed.
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, 8am-4pm.
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/Christine J Saoud/Primary Examiner, Art Unit 1645