Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Applicant’s election of species: HCDRs 1-3 of SEQ ID NOs: 114-115-116 and LCDRs 1-3 of SEQ ID NOs: 120-121-122, corresponding to a VH sequence of SEQ ID NO: 113 and a VL sequence of SEQ ID NO: 112, filed June 15, 2026, is acknowledged.
Claims 2, 14, and 23 have been canceled.
Claims 1, 3-10, 25, 28, and 34-36 have been amended.
It is noted that prior art does not teach or suggest a monoclonal antibody or antigen-binding fragment which is specific for human CXCR5 and comprises the elected CDR combination. Thus, the search is extended to other species encompassed by the claims. Accordingly, the restriction requirement between species, as set forth in the Office action mailed on April 15, 2026, has been reconsidered. The restriction requirement is hereby withdrawn for all pending claims.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a continuation or divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 1, 3-12, 25, 28, 34-36 and 39 are pending and under consideration.
Claim Interpretation
Claim 35 recites “a polynucleotide encoding the VH or the VL chain of the antibody or antigen-binding fragment thereof of claim 1”. Claim 1 recites specific CDRs for VH or VL. Thus, claim 35 is interpretated as encompassing any VH or VL comprising the recited CDR sets of claim 1.
Priority
It is acknowledged that this application is a 371 of Internation Application No. PCT/US2022/019587 filed March 9, 2022, which claims the benefit of priority to U.S. Provisional Patent Appl. No. 63158,462 filed March 9, 2021, and Internation Patent Application No. PCT/CN2021/111049, filed on August 5, 2021.
Certified copies of foreign priority applications have been received as required by 37 CFR 1.55.
The priority date has been established as August 5, 2021.
Information Disclosure Statement
The Information Disclosure Statements filed on 10/20/2023 and 05/06/2024 have been considered and entered by examiner.
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 – Nucleotide and/or amino acid sequences appearing in the drawings e.g. Figs. 1, 2A, 2B, 4A, and 4B are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
According to the Specification filed 09/07/2023, SEQ ID NO: 111 represents a specific sequence (see page 69 of Table D). However, SEQ ID NO: 111 is skipped (000) in Sequence Listing of 09/07/2023.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Claim Objections
Claim 35 is objected to because of the following informalities: “the light VL” should be “the VL” because VL refers to light chain variable region as evidenced by claim 1. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 9, 25 and 34 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 9 recites “the amino acid sequence of SEQ ID NO: 111” which renders the claim indefinite, because according the Table D of Specification, SEQ ID NO: 111 represent a specific sequence. However, SEQ ID NO: 111 is skipped (000) based on Sequence Listing. For the examination purpose, the sequence shown in Table D is used in sequence search.
The phrase “indication with ectopic germinal centers (GCs)” in claim 25 renders the claim indefinite. The phrase lacks clarity because the phrase does not provide an objective criterion for determine which conditions are included. As a result, it is not possible for the skilled person to clearly identify the boundaries of the claim or to determine which conditions are intended to be covered. The scope of the claims is therefore unclear. Incorporating the limitation of claim 28 would overcome the rejection.
Claim 34 is also rejected because it depends on claim 25.
Claim Rejections - 35 USC § 112(d)
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.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 3, which depends on claim 1, recites “wherein the VH sequence has at least 90% sequence identity to any one of the amino acid sequences of SEQ ID NOs: 56 or 65”. However, claim 1(iv) recites “the VH CDR1 sequence, the VH CDR2 sequence, and the VH CDR3 sequence comprise the amino acid sequences of SEQ ID NOs: 33, 49, and 65, respectively”. Thus, claim 3 fails to include all the limitations of claim 1 and broaden the scope of claim 1.
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.
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, 3-12, 25, 28, and 34-36 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. This is a WRITTEN DESCRIPTION rejection.
Claim 1 is drawn an isolated monoclonal antibody, or an antigen-binding fragment thereof, wherein said monoclonal antibody or antigen-binding fragment thereof is specific for human CXCR5, and wherein said monoclonal antibody comprises:(1) a heavy chain variable region (VH), comprising a VH CDR1 sequence, a VH CDR2 sequence, and a VH CDR3 sequence; and/or (2) a light chain variable region (VL), comprising a VL CDR1 sequence, a VL CDR2 sequence, and a VL CDR3 sequence;…”. By reciting comprising (1) or (2), given Broadest Reasonable Interpretation (BRI), claim 1 would encompass a broad genus of antibodies (unlimited number of antibodies) comprising (1) a recited heavy chain variable region only; or (2) a recited light variable region only; or (3) a recited heavy chain variable region paired with an unknown light chain variable region, or (4) a recited light chain variable region paired with an unknown heavy chain variable region. The specification teaches a few CXCR5 antibodies, such as HFB2-4, HFB2-4hzG1, HFB2-4hz, HFB2-5 and HFB2-3 (see Table A-E of the specification). All the antibodies disclosed in the specification comprise a complete set of HCDRs 1-3 and LCDRs1-3.
The specification does not disclose other antibodies with only partial CDR structure (e.g. only HCDRs or only LCDRs) or different CDR combinations, encompassed by the claims with claimed properties, e.g. specific for human CXCR5 or treating diseases (claim 25). Thus, these claims lack written description because the specification lacks a representative number of species that satisfies the entirety of the genus.
Vas-Gath, Inc. v" Mahurkar, 19 USPQ2d 1111, makes clear that "to satisfy the written description requirement, an 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, and that the invention, in that context, is whatever is now claimed".
On 22 February 2018, the USPTO provided a Memorandum clarifying the Written Description Guidelines for claims drawn to antibodies, which can be found at www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf. That Memorandum indicates that, in compliance with recent legal decisions, the disclosure of a fully characterized antigen no longer is sufficient written description of an antibody to that antigen. Accordingly, the instant claims have been evaluated in view of that guidance.
By the time the invention was made, it is well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three "complementarity determining regions" ("CDRs") which provide the majority of the contact residues for the binding of the antibody to its target epitope. Even a single point mutation in HCDR1 region could lead to antibody lose its binding activity (Ni et al., The Protein Journal, 43, pp. 683-696, July 2024, see Abstract). Thus, the specific antibody disclosed by the specification (e.g. 19L04) would not tell structure of other antibodies with CDR variants encompassed by rejected claims. Wong (Wong et al., MABS, 2021, Vol. 13, No. 1, e1873478, Publication Year: 2021) teaches that sequence-distant antibodies can target the same epitope (Abstract).
In view of above, the specification teaches a few antibodies and humanized variants which bind to human CXCR5, are summarized in Tables A-E of the specification. The specification does not disclose any other antibodies which bind to human CXCR5 with only partial CDR structures encompassed by claim 1. In addition, a search of LCDRs 1-3 of SEQ ID NOs: 41-42-43 (claim 1(ii)) identifies antibodies binds to DLL4, as shown below:
PNG
media_image1.png
506
1090
media_image1.png
Greyscale
Thus, only VH or VL cannot determine antigen-binding specificity.
Taken together, one ordinary skill in the art would not be able to visualize other humanized antibody encompassed by the claim which would have the same properties as the ones disclosed in the table above. One of ordinary skill in the art would not be able to readily recognize HCDRs 1-3 combination (except SEQ ID NOs: 33-34-35 disclosed by the specification) can pair with LCDRs 1-3 of SEQ ID NOs: 41-42-43 to form a human CXCR5 binding domain.
In addition, the claims identify the humanized antibodies by function only, where the function is to:
specific for human CXCR5 (claim 1);
treating diseases, such as solid cancer, which would encompass all possible solid cancers.
The specification and prior art have not established the relationship between the claimed functions and the structure of the antibody. One of ordinary skilled in the art would not be able to readily recognize/visualize a humanized antibody with required properties. Cancers are not a single diseases, different cancers may have different origins and different clinical responses. In fact, there is no antibody that can be used to treat all solid cancers. Taken together, applicant has not provided sufficient evidence to show that the inventors possess a genus of humanized antibodies or antigen-binding fragments as claimed.
Claims 3-12 also encompass the isolated antibody or antigen-binding fragment comprising partial CDR structures, thus, these claims lack written description support as set forth above. In addition, Claims 3 and 4 allow up to 10% variations of recited SEQ ID NOs. Given BRI, the claim would encompass variants with mutations at the HCDR or LCDR region. As set forth above, these claims lack written description support for such variants.
In addition, claim 6 encompasses a large number of variants in the frame regions. Regarding up to 10% variation to recited SEQ ID NOs, it is well known that in the variable domain of an antibody, even outside the CDRs, can significantly impact antibody binding. Mutations in the framework regions (non-CDR areas) can alter the structure and dynamics of the antibody, affecting its ability to bind to its target antigen. For example, even single amino acid change in antigen-distal framework position can result in different conformational space and potentially different binding functions, see § Significance on page E486 of Koenig (Koenig et al., PNAS, E486-E495, Publication Date: 01/05/2017). The specification discloses a few framework region variants (see Fig. 4A and 4B, however, claim 6 encompasses a huge number of variants which are not supported by the specification.
In addition, claim 12 encompasses antibody fragment without complete VL and VH , e.g. Fd, V-NAR domain, IgNar, Fcab, or single-domain antibody. As set forth above, the specification lacks written description support for such fragment variants.
Regarding claims 25, 28, 34-37, since the specification does not have the written description support for the antibody or antigen-binding fragment (e.g. all possible VLs can be paired with the recited VH, or all possible VHs can be paired with the recited VLs), logically, the specification would not have the support for nucleic acid encoding the components the antibody or antigen binding fragment, or method of using the antibody or antigen-binding fragment. In addition, Cancer is not a single disease, or cluster of closely related disorders. Thus, cancers are highly heterogeneous at both the molecular and clinical level. Dagogo-Jack et al. (Nature Review Clinical Oncology, vol. 15, pp 81-94, February 2018) teach that cancer is a dynamic disease. During the course of disease, cancers generally become more heterogeneous. As a result of this heterogeneity, the bulk tumor might include a diverse collection of cells harboring distinct molecular signatures with differential levels of sensitivity to treatment. This heterogeneity might result in a non-uniform distribution of genetically distinct tumor-cell subpopulations across and within disease sites (spatial heterogeneity) or temporal variations in the molecular makeup of cancer cells (temporal heterogeneity) (Abstract).
Claim 39 recites the humanize antibodies comprises both a VH sequence and a VL sequence. However, the claim allows up to 10% variations of recited SEQ ID NOs. Given BRI, the claim would encompass variants with mutations at the HCDR or LCDR region. As set forth above, these claims lack written description support for such variants.
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Claims 25, 28 and 34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
“a method of treating Sjogren syndrome (SS) or a cancer expressing CXCR5, the method comprising administering a therapeutically effective amount of an antibody or an antigen-binding fragment thereof of claim 1 to the subject, wherein the antibody or an antigen-binding fragment thereof of claim 1 comprises HCDRs 1-3 of SEQ ID NOs: 114-115-116 and LCDRs 1-3 of SEQ ID NOs: 120-121-122”,
does not reasonably provide enablement for:
a method of treating Sjogren syndrome (SS), a disease or indication with ectopic germinal centers (GCs), lymphoma or leukemia, or solid cancer in a subject in need thereof, the method comprising administering a therapeutically effective amount of an antibody or an antigen-binding fragment thereof of claim 1 to the subject.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. This is a SCOPE OF ENABLEMENT rejection.
To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir.,1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547, the court recited eight factors to consider when assessing whether or not a disclosure would require undue experimentation. These factors are:
1) the quantity of experimentation necessary, 2) the amount of direction or guidance provided, 3) the presence or absence of working examples, 4) the nature of the invention 5) the state of the art, 6) the relative skill of those in the art, 7) the predictability of the art and 8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108,427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
Nature of invention and breadth of the claims:
These claims are drawn to a method of treating Sjogren syndrome (SS), a disease or indication with ectopic germinal centers (GCs), lymphoma or leukemia, or solid cancer in a subject in need thereof, the method comprising administering a therapeutically effective amount of an antibody or an antigen-binding fragment thereof of claim 1 to the subject. As set forth above, these claims encompass a broad genus of antibodies or antigen-binding fragments thereof and/or a broad genus diseases/condition, including unlimited solid cancers, all conditions associated with ectopic germinal centers.
Relative skill in the art:
The relative skill of those in the art is high with an MD or a PhD.
Level of unpredictability in the art and State of the prior art:
Cancer is not a single disease, or cluster of closely related disorders. Thus, cancers are highly heterogeneous at both the molecular and clinical level. Dagogo-Jack et al. (Nature Review Clinical Oncology, vol. 15, pp 81-94, February 2018) teach that cancer is a dynamic disease. During the course of disease, cancers generally become more heterogeneous. As a result of this heterogeneity, the bulk tumor might include a diverse collection of cells harboring distinct molecular signatures with differential levels of sensitivity to treatment. This heterogeneity might result in a non-uniform distribution of genetically distinct tumor-cell subpopulations across and within disease sites (spatial heterogeneity) or temporal variations in the molecular makeup of cancer cells (temporal heterogeneity) (Abstract).
In addition, it is well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three "complementarity determining regions" ("CDRs") which provide the majority of the contact residues for the binding of the antibody to its target epitope. Even a single point mutation in HCDR1 region could lead to antibody lose its binding activity (Ni et al., The Protein Journal, 43, pp. 683-696, July 2024, see Abstract). Thus, the specific antibody disclosed by the specification (e.g. 19L04) would not tell structure of other antibodies with CDR variants encompassed by rejected claims. Wong (Wong et al., MABS, 2021, Vol. 13, No. 1, e1873478, Publication Year: 2021) teaches that sequence-distant antibodies can target the same epitope (Abstract).
Collectively, the therapeutic effectiveness for all diseases (including unlimited solid cancers) of the claimed compositions is not a certainty, and is determined empirically.
Direction or guidance and working examples:
MPEP § 608.01 (p) provided that within the specification, "specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims. The instant specification shows one specific antibody: HFB2-4 and humanized variants thereof which show anti-tumor activity for CXCR5 expressing tumor model (see Examples 2 and 3) and therapeutic activity to Sjogren syndrome (SS). The instant specification does not offer other working examples for other antibodies or antigen-binding fragments for treating other diseases encompassed by the claims.
The quantity of experimentation needed:
The factors outlined in In Re Wands' mentioned above apply here, and in particular as per the MPEP 2164.01 (a): "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." It is very clear that one could not make/use this very broad invention that has no working examples in this unpredictable art without undue experimentation. Genetech Inc vs Nova Nordisk 42 USPQ 2d 1001 "A patent is not a hunting license. It is not a reward for search but compensation for its successful conclusion and patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable."
In order to expand the teaching of the application to treat all diseases with all claimed antibodies or antigen-binding fragments, a considerable amount of experimentation is needed given the unpredictability on function of antibodies and targeted immunotherapy.
Due to the large quantity of experimentation necessary to test the use of claimed compositions to treat various diseases (including all solid cancers); the lack of direction/guidance presented in the specification regarding which structural features are required in order to provide activity; the state of the prior art which establishes the unpredictability of the antibody and cancer therapy; and the breadth of the claims, undue experimentation would be required of the skilled artisan to use the claimed invention in its full scope.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 35 and 37 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Gurney (Gurney et al., US 7750124 B2, Publication Date: 08/07/2008, corresponding to US Application No. 11/905,392).
-As set forth at the beginning of the Office Action, claim 35 is interpreted as encompassing any VH or VL comprising the CDR set recited by claim 1.
Gurney teaches anti-DLL4 antibody comprises a VL of SEQ ID NO: 12 (claims 1-4). As shown below, SEQ ID NO: 12 comprises the SEQ ID NOs: 41-42-43 of the instant application:
US-11-905-392-12
Query Match 78.0%; Score 89.7; Length 111;
Best Local Similarity 29.3%;
Matches 22; Conservative 0; Mismatches 0; Indels 53; Gaps 2;
Qy 1 ESVDNYGISF-----------------AAS------------------------------ 13
|||||||||| |||
Db 27 ESVDNYGISFMKWFQQKPGQPPKLLIYAASNQGSGVPDRFSGSGSGTDFTLTISSLQAED 86
Qy 14 ------QQSKEVPWT 22
|||||||||
Db 87 VAVYYCQQSKEVPWT 101
Thus, SEQ ID NO: 12 of Gurney reads on the VL of the instant claim 35.
Gurney teaches an isolated polynucleotide encoding SEQ ID NO: 12 (see col. 30, 2nd paragraph).
Gurney teaches codons can be optimized for a particular host cell (see 2nd paragraph and the bottom paragraph of col. 38).
Gurney teaches an expression vector comprising the isolated polynucleotide (see col. 30, 3rd paragraph).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 36 is rejected under 35 U.S.C. 103 as being unpatentable over Gurney (Gurney et al., US 7750124 B2, Publication Date: 08/07/2008, corresponding to US Application No. 11/905,392), as applied to claims 35 and 37 above.
Gurney anticipates the instant claims 35 and 37 as set forth above. However, Gurney does not explicitly teach the polynucleotide is codon optimized for expression in a human cell in a single embodiment.
Gurney further teaches that codons can be optimized for a particular host cell (see 2nd paragraph and the bottom paragraph of col. 38), and expressing heavy chain and light chain of antibody in HEK293 cells (a human cell line) (see 3rd paragraph of col. 49, Example 1). It would have prima facie been obvious to one of ordinarily skilled in the art before the time the invention was filed to optimize codon the polynucleotide of VL of Gurney (SEQ ID NO: 12) for expressing the VL in HEK293 cells (a human cell line) to achieve better expression in the host cells.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
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/CHENG LU/ Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/ Supervisory Patent Examiner, Art Unit 1642
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