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 .
Claim Status
Claims 1-9, 11 and 17-19 are currently pending.
It is noted that claims 11 and 17-19 were inadvertently omitted from the groupings in the Lack of Unity mailed on 21 April 2026. However, as indicated in the wording for Group I, the Group was intended to include “antibodies, compositions thereof and therapeutic methods of use”, therefore, claims 11 and 17-19 are properly grouped with Group I.
Election/Restrictions
Applicant's election with traverse of Group I and species C (clone 211B11H10G5) in the reply filed on 22 June 2026 is acknowledged. The traversal is on the ground(s) that there would not be a serious search burden on the examiner if Groups I and II were searched together. This is not found persuasive because the restriction was made under Lack of Unity and search burden is not a consideration for determining Lack of Unity.
The requirement is still deemed proper and is therefore made FINAL.
Claims 8-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 22 June 2026.
Applicant’s statement regarding the amino acid sequences for hu-mAb4 are not consistent with the instant specification. Applicant states at page 6 of the response that hu-mAb4 has a HCV with the amino acid sequence of SEQ ID NO:25 and a LCV with the amino acid sequence of SEQ ID NO:31. However the specification in Example 9 (beginning at page 30) states:
the original heavy chain mVH sequence of molecule c-mAb3 was modified to give 2 humanized sequences huVH3 (SEQ ID NO: 28, VH3) and huVH4 (SEQ ID NO: 30, VH4). (lines 11-12)
the original light chain mVL of molecule c-mAb3 was modified to give 2 humanized sequences huVL3 (SEQ ID NO: 29, VL3) and huVL4 (SEQ ID NO: 31, VL4). (lines 18-19)
The 8 sequences designed above were combined into 4 humanized antibodies hu-mAb1(VH1+VL1), hu-mAb2(VH2+VL2), hu-mAb3(VH3+VL3) and hu-mAb4(VH4+VL4) for subsequent expression validation. c-mAb1 is the parent antibody to hu-mAb1, c-mAb2 is the parent antibody to hu-mAb2, and c-mAb3 is the parent antibody to hu-mAb3 and hu-mAb4. (lines 20-24).
Table 4 at page 31:
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Therefore, Applicant’s assertion of the amino acid sequence structure for hu-mAb4 does not find support in the specification as originally filed.
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 16 June 2023 has been considered by the examiner.
Drawings
The drawings are objected to because they do not comply with 37 CFR 1.84(l) which requires that all drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black, sufficiently dense and dark, and uniformly thick and well-defined. The weight of all lines and letters must be heavy enough to permit adequate reproduction. See representative screenshot of the issue below:
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Figure 1 has panels A-C. 37 CFR 1.84(u)(1) requires that partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. View numbers must be preceded by the abbreviation “FIG”. The panels in Figure 1A-C are not properly labeled. Additionally, the Brief Description of the Drawings should also refer to the partial views according to 37 CFR 1.84(u)(1).
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:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is defective. See item 1) a) or 1) b) above.
The file name which is found in the substitute specification filed 19 February 2026 does not match the file name in the PTO database. See screenshots below:
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The file name must match exactly. The missing text is “103791361_” which should be appended to the beginning of the file name.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it is a single, incomplete sentence. Additionally, the acronym/abbreviation “BCMA” should be spelled out at its first usage. Lastly, speculative applications should not be referred to in the abstract and “prevention of tumor” would be considered speculative in view of the prior art at the time of the instant invention.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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. Additionally, the abbreviation “BCMA” should be spelled out for clarity purposes.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see page 14, line 10 of specification submitted 19 February 2026). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the term TWEEN® (see page 25, line 26; page 27, lines 22 and 25; page 28, line 21; page 29, lines 5 and 9 of the specification filed 19 February 2026), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term BD Accuri™ (see page 26, line 26 of the specification filed 19 February 2026), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The specification at page 31, Table 10 is objected to because it appears to contain an error. Applicant elected the antibody of clone 211B11H10G5 for examination and indicated that humanized antibodies hu-mAB3 and hu-mAB4 were derived from the elected clone. Applicant indicated that hu-mAB4 had a heavy chain variable region with the amino acid sequence of SEQ ID NO:25. However, Table 10 indicates that the HCV of hu-mAB4 is SEQ ID NO:30. The information in the Table appears to be incorrect because the HCV with the amino acid sequence of SEQ ID NO:30 does not contain the CDRs of the elected antibody from clone 211B11H10G5. See alignment below of SEQ ID NO:5 (top line) and SEQ ID NO:30 (bottom line).
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This information is also jumbled in the text describing Example 9 as the text at lines 11-12 are incorrect because the heavy chain of c-mAb3 could not give rise to SEQ ID NO:30 with CDR grafting because the CDRs of c-mAb3 are not contained in SEQ ID NO:30.
Additionally, the amino acid sequences which are indicated to be associated with hu-mAb1 in Table 10 are clearly incorrect as the “heavy chain” is shorter than the “light chain”. Therefore, it is not clear which amino acid sequences should be associated with hu-mAb1.
Applicant should NOTE that correction of these mistakes/inconsistencies will require clear explanation of what the errors are and where the basis for making any corrections/changes comes from in the specification as originally filed. Because Table 10 affirmatively associates the VH1 of hu-mAb1 with SEQ ID NO:24, VL1 of hu-mAb1 with SEQ ID NO:25 and VH4 of hu-mAb4 with SEQ ID NO:30, Applicant will need to point to basis in the specification as originally filed as to why this is not correct and what the correction should be.
Claim Rejections - 35 USC § 112
Claims 1-3 and 7 (and dependent claims 4-6, 11 and 17-19) 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 anti-BCMA antibody/antigen-binding fragment thereof comprising:
an HCDR1, an HCDR2 and an HCDR3 comprised in a heavy chain variable region set forth in SEQ ID NO: 1; and/or an LCDR1, an LCDR2 and an LCDR3 comprised in a light chain variable region set forth in SEQ ID NO: 2;
an HCDR1, an HCDR2 and an HCDR3 comprised in a heavy chain variable region set forth in SEQ ID NO: 3; and/or an LCDR1, an LCDR2 and an LCDR3 comprised in a light chain variable region set forth in SEQ ID NO: 4;
an HCDR1, an HCDR2 and an HCDR3 comprised in a heavy chain variable region set forth in SEQ ID NO: 5; and/or an LCDR1, an LCDR2 and an LCDR3 comprised in a light chain variable region set forth in SEQ ID NO: 6; or
an HCDR1, an HCDR2 and an HCDR3 comprised in a heavy chain variable region; and/or an LCDR1, an LCDR2 and an LCDR3 comprised in a light chain variable region; wherein compared to the heavy chain variable region and/or the light chain variable region according to any of (i) to (iii), at least one CDR of the heavy chain variable region and/or the light chain variable region comprises a mutation that is a substitution, deletion or addition of one or more amino acids (e.g., a substitution, deletion or addition of 1, 2 or 3 amino acids) and is capable of retaining the binding affinity to BCMA.
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 table below and the structural similarity which may be possessed in common (antibody framework structure) is not sufficient to provide for the common use (binding BCMA).
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As demonstrated in Table 4 at page 23, the antibodies have different binding capabilities as antibody 211B11H10G5 can bind monkey BCMA while the other two species of antibody form the other two clones cannot. 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 are 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 4-6, 11 and 17-19 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 1-7, 11 and 17-19 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 “anti-BCMA antibody or an antigen-binding fragment thereof”. Claim 1 only requires the binding domain to comprise 3 CDRs from either the variable heavy chain or the variable light chain and there is no requirement that the CDRs comprise any particular amino acid sequence as the claim recites “variant thereof”. Claim 2 requires both variable heavy and light chains, but does not require that the variable heavy/light chain be from the same antibody and again, the claim encompasses variants. Claim 3 only requires the variable heavy chain or the variable light chain (and variants thereof). Claim 5 encompasses a single-chain antibody. Claim 7 recites that the polypeptide or variant thereof comprises 3 amino acid sequences (presumably, heavy chain CDR regions) “wherein the polypeptide specifically binds to BCMA as part of an anti-BCMA antibody, the antibody further comprising sequences set forth” wherein the sequences recited are presumably light chain CDRs. Claim 7 also includes embodiments where the presumed light chain CDRs are recited with the specifically binding language and the further limitation includes the presumed heavy chain CDRs.
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 6 CDRs with the amino acid sequences of SEQ ID NO:13-15 (heavy chain CDRs) and SEQ ID NO: 22, 17 and 23 (light chain CDRs). An antibody with this complement of CDRs has written description. The elected species also encompass an antibody with a heavy and light chain variable region of SEQ ID NO: 5 and 6, which also has written description. Lastly, the elected species also encompasses a humanized antibody (hu-mAb3) which comprises a heavy and light chain variable region of SEQ ID NO: 28 and 29.
NOTE: While Applicant’s election indicated that humanized antibody hu-mAb4 was encompassed, Applicant stated that the heavy and light chain variable regions comprised the amino acid sequences of SEQ ID NO:25 and 31, respectively. However the instant specification does not provide support for this pairing of sequences and is contrary to the information found in Example 9 and in Table 4. A claim to this pairing would be considered new matter. It is noted that the instant claims do not appear to be directed to this specific pairing.
The instant specification does not describe antibodies which lack a full complement of CDRs and have the ability to bind human BCMA. The instant specification does not teach antibodies with less than a complete completement of CDRs from the same antibody as having the ability to bind human BCMA. The instant specification also does not teach mixing and matching CDRs between antibodies or mixing and matching heavy and light chain variable regions between antibodies. The instant specification does not teach modifications to the disclosed heavy and light chain variable regions from the isolated antibody 211B11H10G5 and especially does not each any variation in the CDRs of the isolated antibody.
The specification fails to provide a written description of the genus of antibodies which lack the 6 CDRs of SEQ ID NO:13-15, 22, 17 and 23 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 only possess 3 of the necessary CDRs or mix and match CDRs and/or heavy/light variable chains and bind human BCMA as required by the claims, and there is no direction provided in the instant specification as to what additional structure would be required in order to obtain an antibody with the necessary binding characteristics and functional characteristics recited in the claims. There is no disclosure that a single domain (comprising 3 CDRs) has the ability to specifically bind human BCMA. 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 human BCMA or have the binding characteristics of the parent antibody (211B11H10G5) which is required by 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 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 comprising 6 CDRs with a heavy chain amino acid sequence of SEQ ID NO:5 and a light chain amino acid sequence of SEQ ID NO:6 and 6 CDRs of SEQ ID NO:13-15, 22, 17 and 23; 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). A review of the language of the claim indicates that these claims are drawn to antibodies which have specific functional characteristics.
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 BCMA antibodies 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).
Additionally, the specification does not provide a written description of an antibody antigen binding fragment that binds human BCMA and only comprises 3 CDRs from one variable chain. A single domain antibody would be an antibody that consists of a single domain from either the heavy chain or light chain. The instant specification fails to describe any such antibody which binds to human BCMA. Single domain antibodies are typically camelid antibodies, but these single domain antibodies cannot be formed by just deleting the light variable chain or the heavy variable chain of a conventional antibody. There is no written description of such and Applicant is not in possession of such an antibody.
In the absence of sufficient recitation of distinguishing characteristics, the specification does not provide adequate written description of the claimed genus, which are antibodies that specifically bind human leptin and which vary from the disclosed BCMA antibody comprising the amino acid sequence structure of SEQ ID NO:5 and 6(light and heavy chains) or SEQ ID NO:13-15, 22, 17 and 23 (6 CDRs). 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 a person 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).
Claims 17-19 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.
Claims 17-19 are not enabled for preventing a tumor by administration of an antibody which binds BCMA because B cells act as both tumor-suppressors and tumor-promotors. The claims fail to recite under which conditions the antibodies should be administered such that administration would result in treating a tumor rather than inhibiting tumor suppression. The claims fail to indicate that the subject being treated has a tumor. The claims fail to indicate what therapeutic effect is to be achieved by the administration. Furthermore, B-cells do not play an active role in all cancer and therefore, inhibition of B-cells would not be expected to treat/prevent any and all tumors as currently claimed.
The prior art of record fails to teach that administration of antibodies which bind BCMA can be administered to prevent a tumor. The instant specification fails to provide any examples of methods of treatment or prevention and the prior art of record does not teach that antibodies which bind BCMA can be used to prevent tumors broadly in a subject. While the art clearly teaches that antibodies to BCMA can reduce tumor load in subjects with multiple myeloma, the antibodies are administered to a subject with multiple myeloma and not to a subject without cancer (i.e. as a prophylactic for prevention as currently claimed) (see Oden et al. Mol. Oncol. 9(7): 1348-1358, 2015).
None of claims 17-19 recite that the subject being administered the anti-BCMA antibody has a tumor or is in need of therapy. The claims also fail to indicate what therapeutic effect is to be achieved by the administration of the anti-BCMA antibody. The claims are clearly not enabled for treatment of a subject who does not have a condition which would require inhibition of BCMA. The claims are also clearly not enabled for treatment of any and all tumors by the administration of an antibody which binds to BCMA because not all tumors are mediated by BCMA and therefore, inhibition of BCMA would not be expected to treat any and all tumors. The instant specification provides no examples of treatment and therefore, no guidance can be gained from the specification with regards to such.
With regard to administration of antibodies which bind BCMA for treating tumors, the art clearly demonstrates that indiscriminate inhibition of B cells would not be considered a treatment for any and all tumors. Sarvaria et al. (B cell regulation in cancer and anti-tumor immunity. Cell. Mol. Immunol. 14: 662-674, 2017) teach that B-cell subsets with distinct phenotypes and functions possess diverse roles in relation to anti-tumor responses. Xu et al. (B cells in tumor metastasis: friend or foe? Int. J. Biol. Sci. 19: 2382-2393, 2023) teach that B cells can inhibit tumor metastasis as well as assisting other immune cells in suppressing tumor metastasis (see page 2384, section 5.1 and 5.2). Xu et al. also teach that B cells can kill tumor cells (see page 2385, section 5.3). Xu et al. also teach that B cells can promote tumor metastasis (see page 2386, section 6), therefore the role of B cells in tumor growth and metastasis is complicated and unpredictable. Lastly, Xu et al. teach that while B-cell immunotherapy has great potential and promising prospects for preventing and treating tumor metastasis, the role of B cells is complex and diverse and current research in this area is limited (see page 2390, last paragraph). One of ordinary skill, in view of the lack of guidance in the specification and the unpredictability of the role of B cells in tumor growth and metastasis would not reasonably conclude that the claims are enabled for treating any and all cancers by the administration of an antibody which binds to BCMA.
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 1-7, 11 and 17-19 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 1 recites an “anti-BCMA antibody or an antigen-binding fragment thereof”. This recitation is indefinite because it is not clear which antigen-binding fragment is intended. Antibodies can bind multiple antigens (the antigen which binds to the variable region as well as Fc receptors on immune cells and complement proteins). Therefore, the claim should clearly indicate the antigen to which the antibody is binding.
Claim 1 recites “the mutation is a conservative amino acid mutation”. However, the recitation of “conservative” is indefinite because it is not clear what is being conserved. Amino acid substitutions can conserve the structure/side chains of the amino acid it is replacing but could also conserve function of the protein into which it is substituted, or both. Therefore, the metes and bounds of the claim cannot be determined.
Claims 1, 2 and 7 recite “retaining the binding affinity to BCMA”. The claim is indefinite because it is not clear which BCMA is intended by the claims. The specification teaches that not all antibodies which were generated bound to BCMA from all species (the elected species of antibody binds to both human and monkey BCMA but other antibodies do not). Therefore, the metes and bounds of “retaining the binding affinity to BCMA” are unclear and therefore, the claims are indefinite.
Regarding claims 1-2, 4, 7 and 11, the phrase “preferably” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention or if they are just preferred embodiments.
Regarding claims 5, 11 and 17, the phrase "for example" (or the abbreviation “e.g.”) renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 11, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 3, 5-6 and 17-19 are indefinite for depending on an indefinite claim.
Allowable Subject Matter
An antibody or antigen-binding fragment thereof which binds to human BCMA and comprises heavy and light chain CDRs comprising the amino acid sequences of SEQ ID NO: 13-15, 22, 17 and 23 would be free of the prior art of record. Additionally, an antibody or antigen-binding fragment thereof which binds to human BCMA comprising the heavy and light chain variable regions of SEQ ID NO: 5 and 6 or SEQ ID NO:28 and 29 would also be free of the prior art of record. A claim to inhibiting human or monkey BCMA by administration of said antibody or antigen-binding fragment thereof would also be free of the prior art of record, including in a subject with a tumor.
Conclusion
No claim is allowed.
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/Christine J Saoud/Primary Examiner, Art Unit 1645
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