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 .
Status of Application, Amendments and/or Claims
The amendment, filed 28 April 2023, has been entered in full. Claims 9-11, 14, 20, 22, 23, 26, 27, 65-95 are canceled. Claims 3, 5-8, 12, 13, 15-19, 21, 24, 25, 28-56, 61-64 are amended.
Applicant’s election without traverse of Group I (claims 1-8, 12, 13, 15-19, 21, 24, 25, 28-38, 44-55, in part, drawn to a therapeutic molecule comprising a hyaluronan-binding domain and a therapeutically active agent, wherein the hyaluronan binding domain comprises at least two link domains of Versican, wherein the active agent comprises an oligopeptide or a protein or a growth factor or an antibody/antigen-binding fragment thereof or a cysteine knot peptide); the species election of an antibody or antigen-binding fragment thereof as the active agent and the species election of a hyaluronan-binding domain of SEQ ID NO: 29 without any point mutations, in the reply filed on 09 June 2026 is acknowledged.
Applicant states that claims 1-8, 12, 30-33, 38, 44-51, and new claims 96-100 read on the elected species.
Claims 13, 15-19, 21, 24, 25, 28, 29, 34-37, 39-43, 52-64 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group (or species), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09 June 2026.
The amendment, filed 09 June 2026, has been entered in full. Claims 39-43 and 55 are canceled. Claims 1, 2, 6, 7, 13, 15-19, 21, 24, 25, 28, 32, 37, 38, 49, and 54 are amended. New claims 96-100 are added. Claims 1-8, 12, 30-33, 38, 44-51 and 96-100 are under examination.
Drawings
The replacement drawings were received on 09 June 2026. These drawings are acceptable.
Information Disclosure Statement
The information disclosure statement(s) (IDS) (filed 7/12/23, 5/16/25 and 6/9/26) were received and comply with the provisions of 37 CFR §§1.97, 1.98 and MPEP § 609. They have been placed in the application file and the information referred to therein has been considered as to the merits.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because the “Sequence Listing XML,” as a separate part of the disclosure, is defective, damaged or unreadable and has not been entered.
Please refer to the document “Sequence Listing in Computer Readable Format is Defective” dated 09 June 2026. Briefly, SEQ ID NOs: 60, 86-90 are variant sequences but are improperly annotated with the feature key “<SITE>” and “<REGION>”.
Required response - Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above submitted in accordance with either item 1. or 2.; together with
o A statement that identifies the location of all additions, deletions or replacements of sequence information relative to the replaced “Sequence Listing XML” as required by 37 CFR 1.835(b)(3);
o A statement that indicates support for the replacement “Sequence Listing XML” in the application, as filed, as required by 37 CFR 1.835(b)(4); and
o A statement that the replacement “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(b)(5).
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125, inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Claim Objections
Claim 30 is objected to because of the following informalities:
Claim 30 has a typo; “antigen-binding fragment” should be “antigen-binding fragment thereof”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 6, 7, 31-33, 50, 96-99 and 100 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. The instant claims are indefinite for the following reasons:
A. Claim 6 and 7 are indefinite because of the limitations, “.. wherein the hyaluronan provides a molar excess of binding equivalents to the at least two link domains of Versican...” and “..wherein the hyaluronan provides a molar ratio of hyaluronan to the therapeutic molecule…”.
Claims 6 and 7 depend from claim 2, which is drawn to a therapeutic molecule comprising an agent (such as an antibody) and a hyaluronan-binding domain (comprising at least two LINK domains of Versican), wherein the hyaluronan-binding domain is bound to a hyaluronan.
It is unclear how the hyaluronan provides something. That is to say, it is unclear if this is a biological function of the hyaluronan protein OR if this is a step wherein the hyaluronan is added in a particular amount. It is noted that the instant claims are drawn to a product, not a method. Clarification is requested. The metes and bounds of claims 6 and 7 cannot be determined.
B. Claims 31, 32, 97, 99 and 100 recite the limitation “capable” (i.e. capable of binding). Capable is a relative term which renders the claims indefinite. Capable is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term “capable” is not a positive recitation and implies that the antibody or antigen-binding fragment thereof may not always bind an antigen. Claims 33, 96 and 98, are included in this rejection insofar as they ultimately depend from claim 31 and do not resolve the issue discussed above.
C. Claim 32 recites the abbreviations/acronyms “VEGF”, “HtrA1”, “IL-33”, “C5”, “Factor P”, “Factor D”, “EPO”, “EPOR”, “IL-1ß”, “IL-17A”, “IL-10”, “TNFα”, “FGFR2”, “PDGF” or “ANG2”, which have not been defined in the claims. Abbreviations and/or acronyms should be defined upon their first use in a claim. The presence of an undefined abbreviation or acronym renders a claim indefinite.
D. Claim 50 is indefinite because of the recitation “..wherein the linker comprises (GxS)n with G = glycine, S = serine and (n = 1, 2, 3, 4, 5, 6, 7, 8, 9 10)”. The instant claim fails to teach what “x” represents. It is noted that limitations from the specification (or any other claim) are not read into claim 50. The metes and bounds of claim 50 cannot be determined.
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.
1. Claims 1-8, 12, 30-33, 38, 44-51 and 96-100 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 specification has written description for:
“A therapeutic molecule targeted to a tissue in a patient, wherein the therapeutic molecule comprises….and a therapeutically active agent wherein the therapeutically active agent is an antibody or antigen-binding fragment thereof that binds to VEGF, IL-6, HtrA1, IL-33, C5, Factor P, Factor D, EPO, EPOR, IL-1β, IL-17A, IL-10, TNFα, FGFR2, PDGF or ANG2….”
but lacks written description for:
“A therapeutic molecule targeted to tissue in a patient, wherein the therapeutic molecule comprises….and a therapeutically active agent wherein the therapeutically active agent is an antibody or antigen-binding fragment thereof that binds an antigen..”.
MPEP § 2163 states: the written description requirement for a claimed genus may be satisfied through establishment of a structure-function correlation (show a structure is correlated with the function) OR through a sufficient description of a representative number of species (show a representative number of species that have the function). There must be enough species that are representative of the full breadth of the genus.
Regarding structure-function correlation: The instant claims encompass a genus of antibodies or antigen-binding fragments thereof that must have the biological function of binding to a target in a tissue of a patient, in particular in the eye of a patient, but lacks any structure.
It is well known in the art that the formation of an intact antigen-binding site of all antibodies requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope (see Al Qaraghuli et al. Antibody protein binding and conformational changes: identifying allosteric signaling pathways to engineer a better effector response. Nature Scientific Reports 10:13969, 2020). Nature Scientific Reports 10:13969, 2020).
Vajdos et al. teach that the specificity and affinity of an antibody for its cognate antigen is determined by the sequence and structure of the variable fragment (Fv): a heterodimer consisting of the N-terminal domains of the heavy and light chains. Even within the Fv, antigen binding is primarily mediated by the complementarity determining regions (CDRs), six hypervariable loops (three each in the heavy and light chains) which together present a large contiguous surface for potential antigen binding. Aside from the CDRs, the Fv also contains more highly conserved framework segments which connect the CDRs and are mainly involved in supporting the CDR loop conformations, although in some cases, framework residues also contact antigen. Vajdos et al. teach that as an important step to understanding how a particular antibody functions, it would be very useful to assess the contributions of each CDR side-chain to antigen binding, and in so doing, to produce a functional map of the antigen-binding site (see, page 416, column bridging paragraph)(see page 416, right column, first paragraph)(see, in particular, Discussion, pages 422-425)(Vajdos et al. Comprehensive functional maps of the antigen-binding site of an anti-ErbB2 antibody obtained with shotgun scanning mutagenesis. J Mol Biol. Vol. 5;320(2):415-28, 2002).
Edwards et al. teach that over 1,000 different antibodies to a single protein can be generated, all with different sequences, and representative of almost the entire extensive heavy and light chain germline repertoire (42/49 functional heavy chain germlines and 33 of 70 V-lambda and V-kappa light chain germlines), and with extensive diversity in the HCDR3 region sequences (that are generated by VDJ germline segment recombination) as well (Edwards et al. The remarkable flexibility of the human antibody repertoire; isolation of over one thousand different antibodies to a single protein, BLyS. Journal of Molecular Biology 334:103-118; 2003).
Based on the teachings, the skilled artisan recognizes that a single protein can be bound by a very large and structurally diverse genus of antibodies (i.e., there is no common structural relationship even for antibodies that bind to the same protein, epitope, or overlapping epitopes). The skilled artisan recognizes that even seemingly minor changes made without guidance or direction as to the relationship between the particular amino acid sequence of the employed antibody (or antigen-binding fragment thereof) and its ability to bind antigen, can dramatically affect antigen-antibody binding.
In the instant case, the claims encompass a plethora of antibodies or antigen-binding fragments thereof that lack any structure but must have the claimed function.
Regarding a representative number of species: the instant specification fails to describe a representative number of species to provide adequate written description of the claimed genus as per MPEP § 2163. There must be enough species that are representative of the full breadth of the genus.
The instant specification teaches examples of antibodies that bind VEGF, IL6, HtrA1, IL-33, C5, Factor P, Factor D, EPO, EPOR, IL-1β, IL-17A, IL-10, TNFα, FGFR2, PDGF or ANG2.
However, the presented antibodies and antigen-binding fragments thereof are not representative of an entire genus of antibodies and antigen-binding fragments thereof comprising an unlimited number of individual and combinational substitutions, deletions and/or additions with the function of binding any antigen in a tissue (or eye) of a patient.
The skilled artisan cannot envision the detailed chemical structure of the encompassed genus. The scope of the claims include numerous structural variants, and the genus is highly variant because a significant number of structural differences between genus members is permitted. Because the disclosure fails to describe the common attributes or characteristics that identify substitution, deletion and addition variant members of the genus, and because the genus is highly variant, the disclosed antibodies are insufficient to describe the genus. The level of skill and knowledge in the art is such that one of ordinary skill would not be able to identify without further testing which antibodies (or antigen-binding fragments thereof) have the claimed activity.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 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 is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) 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). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of antibodies or antigen-binding fragments thereof with the biological function of binding antigens in patient tissue, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. There is no teaching in the specification regarding which percentage of the structure can be varied while retaining the claimed function. There is no evidence that the disclosed antibodies (or antigen-binding fragment thereof) are representative of the genus of antibodies encompassed by the instant claims.
Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, only an antibody or antigen-binding fragment thereof that binds to VEGF, IL-6, HtrA1, IL-33, C5, Factor P, Factor D, EPO, EPOR, IL-1β, IL-17A, IL-10, TNFα, FGFR2, PDGF or ANG2, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph.
2. Claim 100 is 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 New Matter Rejection.
The specification as originally filed does not provide support for the invention as now claimed: “a bispecific antibody or antigen-binding fragment thereof that binds VEGF and IL-6".
Applicant's amendment, filed 09 June 2026, asserts that no new matter has been added and directs support to paragraphs 0251, 0253 and 0255, for the written description for the above-mentioned “limitations”.
The wording or connotation of the instant claims is not apparent from said sections. The Examiner has copied paragraphs 0251-0256 from the substitute specification submitted on 6/9/2026.
[0251] In some embodiments, the antibody or antigen-binding fragment thereof comprises a bispecific antibody, an antibody lacking at least the Fc domain, a Fab fragment, a (Fab')₂ fragment, a Fab' fragment, VhH fragment, scFv fragment, scFv-Fc fragment, or minibody.
[0252] In some embodiments, the antibody or antigen-binding fragment thereof binds to an antigen that is present in the eye. In some embodiments, the antibody or antigen-binding fragment thereof may bind to VEGF, HtrA1, IL-33, C5, Factor P, Factor D, EPO, EPOR, IL-1ß, IL-17A, IL-10, TNFα, FGFR2, PDGF, or ANG2.
[0253] In some embodiments, the first component is an anti-VEGF antibody or antibody-binding fragment, an anti-PDGF antibody or antibody-binding fragment, an anti-ANG2 antibody or antibody-binding fragment, or an anti-IL-1β antibody or antibody-binding fragment. Examples of antibodies that bind VEGF include Lucentis® (ranibizumab), Eylea® (aflibercept), Beovu® (brolucizumab-dbll), and Avastin® (bevacizumab).
[0254] In some embodiments, the antibody comprises a bispecific antibody. In some embodiments, the bispecific antibody is an anti-VEGF/anti-Ang2 bispecific antibody, such as RG-7716 or any bispecific anti-VEGF/anti-Ang2 bispecific antibody disclosed in WO 2010/069532 or WO 2016/073157 or a variant thereof. In some embodiments, the bispecific antibody is an anti- VPDF antibody, i.e., an anti-VEGF and anti-PDGF dutaFab antibody.
[0255] In some embodiments, the first component is an anti-IL-6 antibody, for example, EBI-031 (Eleven Biotherapeutics; see, e.g., WO 2016/073890), siltuximab (SYLVANT), olokizumab, clazakizumab, sirukumab, elsilimomab, OPR-003, MEDI5117, PF-04236921, or a variant thereof.
The Examiner cannot find a teaching of a bispecific antibody (or antigen-binding fragment thereof) that binds both VEGF and IL-6.
The specification as filed does not provide a written description or set forth the metes and bounds of this "limitations". The instant claims now recite limitations which were not disclosed in the specification as filed, and now change the scope of the instant disclosure as-filed.
Applicant is required to cancel the new matter in the response to this Office action. Alternatively, Applicant is invited to provide specific written support for the “limitations” indicated above or rely upon the limitations set forth in the specification as filed.
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.
Claim(s) 1-4, 6-8, 30-33, 38, 44-47, 96-98 are rejected under 35 U.S.C. 102(a1) and 35 U.S.C. 102(a2) as being anticipated by Ghosh et al. (Reference submitted by Applicant, US 2017/0290876; published October 12, 2017) as evidenced by LeBaron et al. (Hyaluronate Binding Properties of Versican. The Journal of Biological Chemistry. Vol. 267, No. 14, Issue of May 15, pp. 10003-10010,1992).
Ghosh et al. teach peptide tags that bind to hyaluronan (HA)(abstract, 0003 and 0004). Ghosh et al. teach “hyaluronan binding proteins” or “HA binding proteins” refers to a protein or a family of proteins that bind hyaluronan (HA). Ghosh et al. teach that examples of HA binding proteins are known in the art and include Versican, CD44, RHAMM, Aggrecan, bacterial HA synthase, collagen VI, and TSG-6. Ghosh et al. teach that many HA binding proteins or peptide fragments contain a common structural domain of ˜100 amino acids in length involved in HA binding and that the name of the structural domain is referred to as a “LINK Domain” (para 0046)(applies to claim 1). Ghosh et al. teach that the peptide tag comprises a LINK Domain and binds hyaluronan (HA) (para 0130)(applies to claim 1). Ghosh et al. teach a therapeutic molecule comprising a peptide tag (comprising a hyaluronan binding domain from CD44 or TSG-6) that is attached to an antibody via a peptide linker (Table 3, pages 56-58)(applies to claims 1, 30 and 31).
Versican comprises link domains and binds hyaluronan (HA) via its hyaluronan-binding domain as evidenced by LeBaron (abstract, page 10003, Figure 1 at page 10006 and Discussion at page 10009)(LeBaron et al. Hyaluronate Binding Properties of Versican. The Journal of Biological Chemistry. Vol. 267, No. 14, Issue of May 15, pp. 10003-10010,1992)(applies to claim 1).
Ghosh et al. teach ocular hyaluronan (HA) mainly consists of high molecular weight polymers (>0.5×10̂5daltons, i.e., greater than 500 kDa)(para 0108). Ghosh et al. teach a modified antibody of interest was allowed to associate with hyaluronan (HA) on the biosensor for 900 seconds, and after which was transferred and dipped in well containing Kinetic Buffer for 2100 seconds to allow dissociation of the modified antibody from hyaluronan (HA) Ghosh et al. teach using a hyaluronan (HA) with a molecular weight of 17 kDa (para 0288)(applies to claims 2-4).
Chemical compounds and their properties are inseparable (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA1963)), as are their processes and yields (In re Von Schickh, 362 F.2d 821, 150 USPQ 300 (CCPA 1966)). Therefore, the hyaluronan in a
therapeutic molecule comprising an active agent such as an antibody linked to a hyaluronan-binding domain comprising at least two link domains of Versican bound to hyaluronan, will provide a molar excess of binding equivalents to the at least two link domains of Versican and a molar ratio of hyaluronan to the therapeutic molecule that ranges from 1.5:1 to 1:1 (applies to claims 6 and 7). The hyaluronan-binding domain in a therapeutic molecule comprising an active agent such as an antibody linked to a hyaluronan-binding domain comprising at least two link domains of Versican will have a KD of 5 nM to 10 um (applies to claim 8).
Ghosh et al. teach that the peptide tags can be linked to an antibody or an antigen-binding fragment thereof, such as an antibody that binds VEGF or interleukins such as IL-1B and IL-17A (paras 0004 and 0116) (applies to claims 30-33). Gosh et al. teach that the peptide tag can be linked to anti-VEGF antibodies such as ranibizumab, bevacizumab or aflibercept (paras 0117 and 0142)(applies to claim 38).
Ghosh et al. teach that the peptide tag can be linked to the antibody or antigen-binding fragment thereof by covalently linking via a peptide linker. Ghosh et al. teach that the peptide linkers may be, for example, about 2 to 25 residues in length. Ghosh et al. teach linkers such as GSGGG (paras 0005, 0062, 0063 and 0072 and page 23).
(applies to claims 44-47). Ghosh et al. teach antibodies include antibodies, antigen-binding fragments thereof, bispecific antibodies, antigen-binding fragments thereof and bivalent fragment comprising two Fab fragments (paras 0027 and 0198-0204)(applies to claims 96-98).
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.
1. Claims 1-8, 30-33, 38, 44-47, 96-98 are rejected under 35 U.S.C. 103 as being unpatentable over Ghosh et al. (US 2017/0290876; published October 12, 2017) as evidenced by LeBaron et al. (The Journal of Biological Chemistry. Vol. 267, No. 14, Issue of May 15, pp. 10003-10010,1992) in view of Tolg et al. (A RHAMM Mimetic Peptide Blocks Hyaluronan Signaling and Reduces Inflammation and Fibrogenesis in Excisional Skin Wounds. Am J Pathol Vol. 181:1250–1270; 2012).
Ghosh et al. teach peptide tags that bind to hyaluronan (HA)(abstract, 0003 and 0004). Ghosh et al. teach “hyaluronan binding proteins” or “HA binding proteins” refers to a protein or a family of proteins that bind hyaluronan (HA). Ghosh et al. teach that examples of HA binding proteins are known in the art and include Versican, CD44, RHAMM, Aggrecan, bacterial HA synthase, collagen VI, and TSG-6. Ghosh et al. teach that many HA binding proteins or peptide fragments contain a common structural domain of ˜100 amino acids in length involved in HA binding and that the name of the structural domain is referred to as a “LINK Domain” (para 0046)(applies to claim 1). Ghosh et al. teach that the peptide tag comprises a LINK Domain and binds hyaluronan (HA) (para 0130)(applies to claim 1). Ghosh et al. teach a therapeutic molecule comprising a peptide tag (comprising a hyaluronan binding domain from CD44 or TSG-6) that is attached to an antibody via a peptide linker (Table 3, pages 56-58)(applies to claim 1).
Versican comprises link domains and binds hyaluronan (HA) via its hyaluronan-binding domain as evidenced by LeBaron (abstract, page 10003, Figure 1 at page 10006 and Discussion at page 10009)(LeBaron et al. Hyaluronate Binding Properties of Versican. The Journal of Biological Chemistry. Vol. 267, No. 14, Issue of May 15, pp. 10003-10010,1992)(applies to claim 1).
Ghosh et al. teach ocular hyaluronan (HA) mainly consists of high molecular weight polymers (>0.5×10̂5daltons; i.e., greater than 500 kDa)(para 0108). Ghosh et al. teach a modified antibody of interest was allowed to associate with hyaluronan (HA) on the biosensor for 900 seconds, and after which was transferred and dipped in well containing Kinetic Buffer for 2100 seconds to allow dissociation of the modified antibody from hyaluronan (HA) Ghosh et al. teach using a hyaluronan (HA) with a molecular weight of 17 kDa (para 0288)(applies to claims 2-4).
Ghosh et al. do not teach wherein the hyaluronan (HA) is 10 kDa (claim 5).
Tolg et al. teach during wound repair, hyaluronan (HA) synthesis is required for mesenchymal differentiation, including transforming growth factor B1-mediated differentiation of myofibroblasts, collagen production by dermal fibroblasts, and endothelial cell proliferation and migration. Tolg teach native high molecular weight HA (e.g., greater than 500 kDa) reduces inflammation and angiogenesis, and during skin excisional wound repair, increases the expression of transforming growth factor B, metalloproteinase 1 and 3 (MMP1, -3), and collagen III (Col3A1) in human dermal fibroblasts. Tolg et al. teach, by contrast, fragmented HA that is present in intermediate sizes (50 to 400 kDa), and as smaller oligosaccharides (less than 20 kDa), promotes inflammation, angiogenesis, and migration of most cell types involved in tissue repair. Tolg et al. teach the biological differences of native HA versus fragments are due in part to their ability to activate specific signaling cascades through HA receptors such as CD44 (cluster designation 44), receptor for hyaluronan mediated motility (RHAMM; human form, HMMR) and Toll-like receptors 2 and 4 (TLR-2, -4)(page 1250-1251). Tolg et al. teach identifying a 15-mer peptide that is highly homologous to the hyaluronan-binding domain in RHAMM using hyaluronan with a molecular weight of 10 kDa (abstract and page 1257, last paragraph)(applies to claim 5).
It would have been obvious for one of ordinary skill in the art before the effective filling date to modify a therapeutic molecule comprising an antibody and a Versican hyaluronan-binding domain comprising at least two-link domains, wherein the antibody is linked covalently to the Versican hyaluronan-binding domain via a peptide linker, wherein the Versican hyaluronan-binding domain that comprises at least two-link domains is bound to hyaluronan via the hyaluronan-binding domain, as taught by Ghosh and evidenced by LeBaron, by having a hyaluronan that is 10 kDa, as taught by Tolg.
One of ordinary skill in the art before the effective filing date, would have been motivated to make such modifications and expect success for the following reasons Ghosh et al. teach ocular hyaluronan (HA) mainly consists of high molecular weight polymers that are greater than 500 kDa. Ghosh et al. teach using a hyaluronan (HA) with a molecular weight of 17 kDa. Tolg et al. teach native high molecular weight HA (e.g., greater than 500 kDa) reduces inflammation and angiogenesis; but fragmented HA in intermediate sizes (50 to 400 kDa), and smaller oligosaccharides (less than 20 kDa), promotes inflammation, angiogenesis, and migration of most cell types involved in tissue repair. Tolg et al. teach that HA fragments have the ability to activate specific signaling cascades through HA receptors. Tolg et al. teach identifying a peptide that is highly homologous to the hyaluronan-binding domain in RHAMM using hyaluronan with a molecular weight of 10 kDa. Thus, it would be obvious that the hyaluronan bound to the hyaluronan-binding domain in the therapeutic molecule would be 10 kDa.
2. Claims 1-4, 6-8, 12, 30-33, 38, 44-47, 96-100 are rejected under 35 U.S.C. 103 as being unpatentable over Ghosh et al. (US 2017/0290876; published October 12, 2017) as evidenced by LeBaron et al. (Hyaluronate Binding Properties of Versican. The Journal of Biological Chemistry. Vol. 267, No. 14, Issue of May 15, pp. 10003-10010,1992) in view of Jiang et al. (US 2013/0202583; published August 8, 2013) and Beckmann (US 2014/0206846; published July 24, 2014).
Ghosh et al. teach peptide tags that bind to hyaluronan (HA)(abstract, 0003 and 0004). Ghosh et al. teach “hyaluronan binding proteins” or “HA binding proteins” refers to a protein or a family of proteins that bind hyaluronan (HA). Ghosh et al. teach that examples of HA binding proteins are known in the art and include Versican, CD44, RHAMM, Aggrecan, bacterial HA synthase, collagen VI, and TSG-6. Ghosh et al. teach that many HA binding proteins or peptide fragments contain a common structural domain of ˜100 amino acids in length involved in HA binding and that the name of the structural domain is referred to as a “LINK Domain” (para 0046)(applies to claim 1). Ghosh et al. teach that the peptide tag comprises a LINK Domain and binds hyaluronan (HA) (para 0130)(applies to claim 1). Ghosh et al. teach a therapeutic molecule comprising a peptide tag (comprising a hyaluronan binding domain from CD44 or TSG-6) that is attached to an antibody via a peptide linker (Table 3, pages 56-58)(applies to claims 1, 30 and 31).
Versican comprises link domains and binds hyaluronan (HA) via its hyaluronan-binding domain as evidenced by LeBaron (abstract, page 10003, Figure 1 at page 10006 and Discussion at page 10009)(LeBaron et al. Hyaluronate Binding Properties of Versican. The Journal of Biological Chemistry. Vol. 267, No. 14, Issue of May 15, pp. 10003-10010,1992)(applies to claim 1).
Ghosh et al. teach that the peptide tags can be linked to an antibody or an antigen-binding fragment thereof, such as an antibody that binds VEGF or interleukins such as IL-1B and IL-17A (paras 0004 and 0116) (applies to claims 30-33). Ghosh et al. teach antibodies include antibodies, antigen-binding fragments thereof, bispecific antibodies, antigen-binding fragments thereof and bivalent fragment comprising two Fab fragments (paras 0027 and 0198-0204)(applies to claims 96-98).
Ghosh et al. do not teach a hyaluronan-binding domain that is at least 95% identical to instant SEQ ID NO: 29. Ghosh et al. do not teach bispecific antibodies that bind VEGF and interleukin-6 (IL-6).
Jiang et al. teach Versican as a hyaluronan binding protein (HABP) that contains two or more link modules (para 0015). Jiang et al. teach a Versican sequence that is at least 95% identical to instant SEQ ID NO:29 (see below, Sequence Search Result A and Jiang et al. at page 26, para 0233)(applies to claim 12).
Beckmann teaches bispecific antibodies and functional fragments thereof that bind VEGF and IL-6. Beckmann teaches the analysis of parental and bi-specific antibodies against VEGF and IL6 (paras 0002 and 0066). Beckmann teaches using antigens VEGF and IL-6 wherein parental antibody IL6P and parental antibody VEGFP were combined to yield the bi-specific antibody VH6L that binds VEGF and
IL-6 (paras 0129 and 0137)(applies to claims 96, 97, 99 and 100).
It would have been obvious for one of ordinary skill in the art before the effective filling date to modify a therapeutic molecule comprising an antibody and a Versican hyaluronan-binding domain comprising at least two-link domains, wherein the antibody is linked covalently to the Versican hyaluronan-binding domain via a peptide linker, wherein the antibody can be a bispecific antibody that binds VEGF, as taught by Ghosh and evidenced by LeBaron, by using a bispecific antibody that binds to VEGF and IL-6, as taught by Beckmann and a hyaluronan-binding domain comprising the sequence taught by Jiang et al.
One of ordinary skill in the art before the effective filing date, would have been motivated to make such modifications and expect success because Ghosh teaches bispecific antibodies that bind VEGF and a different epitope. Using a bispecific antibody that binds VEGF and IL6, as taught by Beckmann, is a way to achieve binding to two structurally unrelated epitopes. Lastly, having the sequence of the Versican hyaluronan-binding domain, as taught by Jiang, allows the ease of the protein to be made recombinantly.
3. Claims 1-4, 6-8, 30-33, 38, 44-49, 51, and 96-98 are rejected under 35 U.S.C. 103 as being unpatentable over Ghosh et al. (US 2017/0290876; published October 12, 2017) as evidenced by LeBaron et al. (Hyaluronate Binding Properties of Versican. The Journal of Biological Chemistry. Vol. 267, No. 14, Issue of May 15, pp. 10003-10010,1992) in view of Ashman et al. (US Patent 8,680,245; published March 25, 2014).
Ghosh et al. teach peptide tags that bind to hyaluronan (HA)(abstract, 0003 and 0004). Ghosh et al. teach “hyaluronan binding proteins” or “HA binding proteins” refers to a protein or a family of proteins that bind hyaluronan (HA). Ghosh et al. teach that examples of HA binding proteins are known in the art and include Versican, CD44, RHAMM, Aggrecan, bacterial HA synthase, collagen VI, and TSG-6. Ghosh et al. teach that many HA binding proteins or peptide fragments contain a common structural domain of ˜100 amino acids in length involved in HA binding and that the name of the structural domain is referred to as a “LINK Domain” (para 0046)(applies to claim 1). Ghosh et al. teach that the peptide tag comprises a LINK Domain and binds hyaluronan (HA) (para 0130)(applies to claim 1). Ghosh et al. teach a therapeutic molecule comprising a peptide tag (comprising a hyaluronan binding domain from CD44 or TSG-6) that is attached to an antibody via a peptide linker (Table 3, pages 56-58)(applies to claim 1).
Versican comprises link domains and binds hyaluronan (HA) via its hyaluronan-binding domain as evidenced by LeBaron (abstract, page 10003, Figure 1 at page 10006 and Discussion at page 10009)(LeBaron et al. Hyaluronate Binding Properties of Versican. The Journal of Biological Chemistry. Vol. 267, No. 14, Issue of May 15, pp. 10003-10010,1992)(applies to claim 1).
Ghosh et al. teach that the peptide tag can be linked to the antibody or antigen-binding fragment thereof by covalently linking via a peptide linker. Ghosh et al. teach that the peptide linkers may be, for example, about 2 to 25 residues in length. Ghosh et al. teach linkers such as GSGGG (paras 0005, 0062, 0063 and 0072 and page 23)(applies to claims 44-47).
Ghosh et al. do not teach the peptide linkers as recited in instant claims 48, 49 and 51.
Ashman et al. teach that the present invention relates to anti-IL-13 antibodies and pharmaceutical formulations containing them (abstract). Ashman et al. teach that the antibodies of the present invention can be linked to one or more epitope-binding domains (column 2, lines 50-62). Ashman et al. teach epitope-binding domains include molecules such as CTLA-4; lipocalin; Heat shock proteins such as GroEI and GroES; transferin; ankyrin repeat protein (DARPin); peptide aptamer; C-type lectin domain; human .gamma.-crystallin and human ubiquitin; PDZ domains; scorpion toxinkunitz type domains of human protease inhibitors; and fibronectin (adnectin) (column 7, lines 22-30). Ashman et al. teach peptide linkers to link the antibody to the molecule such as GGGGS and GSGSGSGSGSGSGSGSGSGSTVAAPSGSTVAAPSGS (column 15, lines 10-24 and column 15, lines 39-63)(applies to claims 48, 49 and 51).
It would have been obvious for one of ordinary skill in the art before the effective filling date to modify a therapeutic molecule comprising an antibody and a Versican hyaluronan-binding domain comprising at least two-link domains, wherein the antibody is linked covalently to the Versican hyaluronan-binding domain via a peptide linker, as taught by Ghosh and evidenced by LeBaron, using the peptide linkers taught by Ashman et al. One of ordinary skill in the art before the effective filing date, would have been motivated to make such modifications and expect success because the linkers taught by Ghosh and Ashman are obvious versions of peptide linkers comprising a series of glycine and serine residues that are employed in the art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-8, 30-33, 44-51, 96-100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-10, 27 of copending Application No. 18/301,187 in view of Ghosh et al. (US 2017/0290876; published October 12, 2017) and Beckmann (US 2014/0206846; published July 24, 2014) and as evidenced by LeBaron et al. (The Journal of Biological Chemistry. Vol. 267, No. 14, Issue of May 15, pp. 10003-10010,1992).
The instant claims are drawn to a therapeutic molecule targeted to a tissue in a patient, wherein the therapeutic molecule comprises a hyaluronan-binding domain and a therapeutically active agent, wherein the hyaluronan-binding domain comprises at least two link domains of Versican. The claims are drawn to a therapeutic molecule targeted to a tissue in a patient, wherein the therapeutic molecule comprises a hyaluronan-binding domain and a therapeutically active agent, wherein the hyaluronan-binding domain comprises at least two link domains of Versican that are bound to a hyaluronan via the HA-binding hyaluronan-binding domain. The claims are further drawn to wherein the hyaluronan ranges from 400 Da to 200 kDa, is at least 5 kDa or is 10 kDa. The claims are further drawn to wherein the therapeutic agent comprises an antibody or antigen-binding fragment thereof, wherein the agent can bind VEGF, IL-6, HtrA1, IL-33, C5, Factor P, Factor D, EPO, EPOR, IL- 1ß, IL-17A, IL-10, TNFα, FGFR2, PDGF or ANG2. The claims are further drawn to wherein the therapeutically active agent and the hyaluronan-binding domain are covalently linked via a linker. The claims are further drawn to wherein the antibody or an antigen-binding fragment thereof is a bispecific antibody or antigen-binding fragment thereof, wherein the bispecific antibody or antigen-binding fragment thereof binds VEGF and wherein the bispecific antibody or antigen-binding fragment thereof is a dual-targeting Fab (dutaFab). The claims are further drawn to wherein the bispecific antibody or antigen-binding fragment thereof binds VEGF and IL6.
The claims of copending Application No. 18/301,187 teach a therapeutic molecule comprising a first component capable of binding to a therapeutic target in the eye, one or more second components capable of binding to hyaluronan, wherein the one or more second components are covalently bound to the first component, and optionally, one or more third components comprising hyaluronan, wherein, if present, the one or more third components are non-covalently bound to the one or more second components. The claims further teach wherein the first component is an antibody, antigen-binding fragment, particularly an antibody fragment, more particularly an antibody fragment lacking at least the Fc domain, especially wherein the fragment is or comprises an (Fab')₂ fragment, Fab' fragment, Fab fragment, VhH fragment, scFv fragment, scFv-Fc fragment, and minibody, more especially a Fab fragment. The claims further teach wherein the third component is a hyaluronan and has a molecular weight chosen from 3 kDa to 60 kDa, from 4 kDa to 30 kDa, from 5 kDa to 20 kDa, or from 400 Da to 200 kDa or provides a molar excess of binding equivalents to the one or two second components. The claims further teach wherein the one or two second components are directly bound to the first component or bound indirectly to the first component via a linker. The claims further teach wherein the therapeutic target is VEGF, C2, C3a, C3b, C5, C5a, HtrA1, IL-33, Factor P, Factor D, EPO, EPOR, IL-1ß, IL-17A, IL-10, TNFα, FGFR2, PDGF or ANG2. The claims further teach wherein first component is an antibody or antigen-binding fragment against VEGF and/or the third component is a hyaluronan of a molecular weight of from 5 kDa to 20 kDa. The claim further teach a pharmaceutical composition comprising the therapeutic molecule and a pharmaceutically acceptable excipient, diluent or carrier.
The claims of copending Application No. 18/301,187 do not teach wherein the second component that binds to hyaluronan is Versican. The claims of copending Application No. 18/301,187 do not teach a bispecific antibody or antigen-binding fragment thereof that binds to VEGF and IL-6.
Ghosh et al. teach peptide tags that bind to hyaluronan (HA)(abstract, 0003 and 0004). Ghosh et al. teach “hyaluronan binding proteins” or “HA binding proteins” refers to a protein or a family of proteins that bind hyaluronan (HA). Ghosh et al. teach that examples of HA binding proteins are known in the art and include Versican, CD44, RHAMM, Aggrecan, bacterial HA synthase, collagen VI, and TSG-6. Ghosh et al. teach that many HA binding proteins or peptide fragments contain a common structural domain of ˜100 amino acids in length involved in HA binding and that the name of the structural domain is referred to as a “LINK Domain” (para 0046). Ghosh et al. teach that the peptide tag comprises a LINK Domain and binds hyaluronan (HA) (para 0130). Ghosh et al. teach a therapeutic molecule comprising a peptide tag (comprising a hyaluronan binding domain from CD44 or TSG-6) that is attached to an antibody via a peptide linker (Table 3, pages 56-58).
Versican comprises link domains and binds hyaluronan (HA) via its hyaluronan-binding domain as evidenced by LeBaron (abstract, page 10003, Figure 1 at page 10006 and Discussion at page 10009)(LeBaron et al. Hyaluronate Binding Properties of Versican. The Journal of Biological Chemistry. Vol. 267, No. 14, Issue of May 15, pp. 10003-10010,1992).
Beckmann teaches bispecific antibodies and functional fragments thereof that bind VEGF and IL-6. Beckmann teaches the analysis of parental and bi-specific antibodies against VEGF and IL6 (paras 0002 and 0066). Beckmann teaches using antigens VEGF and IL-6 wherein parental antibody IL6P and parental antibody VEGFP were combined to yield the bi-specific antibody VH6L that binds VEGF and IL-6 (paras 0129 and 0137).
It would have been obvious for one of ordinary skill in the art before the effective filling date to modify a therapeutic molecule comprising a first component capable of binding to a therapeutic target in the eye (such as an antibody or antigen-binding fragment), a second components that binds to hyaluronan, wherein the second components is covalently bound to the first component via a linker, and optionally, a third components comprising hyaluronan, wherein, if present, binds non-covalently to the second components, as taught by the claims of copending Application No. 18/301,187, by using a Versican hyaluronan-binding domain comprising at least two-link domains, wherein the Versican hyaluronan-binding domain comprising at least two-link domains binds hyaluronan, as taught by Ghosh and evidenced by LeBaron, wherein the first component is an antibody or antigen-binding fragment thereof that binds to VEGF or a bispecific antibody or antigen-binding fragment thereof that binds to VEGF and IL6, as taught by Ghosh and Beckmann, respectively.
One of ordinary skill in the art before the effective filing date, would have been motivated to make such modifications and expect success for the following reasons.
The claims of copending Application No. 18/301,187 recite antibodies (first component) and hyaluronan (third component) that overlap in scope with the instant claims. Ghosh et al. teach that hyaluronan is found in the eye. Ghosh et al. teach hyaluronan binding proteins (second component) include Versican. Ghosh teaches bispecific antibodies that bind VEGF and a different epitope. Using a bispecific antibody that binds VEGF and IL6, as taught by Beckmann, is a way to achieve binding to two structurally unrelated epitopes.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/R.M.D/Examiner, Art Unit 1647 6/14/2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
SEQUENCE SEARCH RESULT A
This page gives you Search Results detail for the Application 18301180 and Search Result 20260612_172046_us-18-301-180-29.rapbm
Title: US-18-301-180-29
Perfect score: 1850
Sequence: 1 LHKVKVGKSPPVRGSLSGKV..........DAYCFKPKEGNSHHHHHHHH 341
SUMMARIES
%
Result Query Filing
No. Score Match Length ID Date
-------------------------------------------------------------------------------------------------------------
39 1771 95.7 2376 US-13-694-071-235 2012-10-24 Companion Diagnostic for Anti-Hyaluronan Agent Therapy and Methods of Use Thereof
RESULT 39
US-13-694-071-235
(NOTE: this sequence has 3 duplicates in the database searched.
See complete list at the end of this report)
Sequence 235, US/13694071
Publication No. US20130202583A1
GENERAL INFORMATION
APPLICANT: Jiang, Ping
APPLICANT: Shepard, H. Michael
APPLICANT: Huang, Lei
TITLE OF INVENTION: Companion Diagnostic for Anti-Hyaluronan
TITLE OF INVENTION: Agent Therapy and Methods of Use Thereof
FILE REFERENCE: 33320.03096.US04/3096
CURRENT APPLICATION NUMBER: US/13/694,071
CURRENT FILING DATE: 2012-10-24
PRIOR APPLICATION NUMBER: 61/628,187
PRIOR FILING DATE: 2011-10-24
PRIOR APPLICATION NUMBER: 61/559,011
PRIOR FILING DATE: 2011-11-11
PRIOR APPLICATION NUMBER: 61/630,765
PRIOR FILING DATE: 2011-12-16
PRIOR APPLICATION NUMBER: 61/714,700
PRIOR FILING DATE: 2012-10-16
NUMBER OF SEQ ID NOS: 426
SEQ ID NO 235
LENGTH: 2376
TYPE: PRT
ORGANISM: Homo sapiens
FEATURE:
OTHER INFORMATION: human Versican protein P13611
Query Match 95.7%; Score 1771; Length 2376;
Best Local Similarity 99.1%;
Matches 330; Conservative 1; Mismatches 2; Indels 0; Gaps 0;
Qy 1 LHKVKVGKSPPVRGSLSGKVSLPCHFSTMPTLPPSYNTSEFLRIKWSKIEVDKNGKDLKE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 LHKVKVGKSPPVRGSLSGKVSLPCHFSTMPTLPPSYNTSEFLRIKWSKIEVDKNGKDLKE 80
Qy 61 TTVLVAQNGNIKIGQDYKGRVSVPTHPEAVGDASLTVVKLLASDAGLYRCDVMYGIEDTQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 TTVLVAQNGNIKIGQDYKGRVSVPTHPEAVGDASLTVVKLLASDAGLYRCDVMYGIEDTQ 140
Qy 121 DTVSLTVDGVVFHYRAATSRYTLNFEAAQKACLDVGAVIATPEQLFAAYEDGFEQCDAGW 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 DTVSLTVDGVVFHYRAATSRYTLNFEAAQKACLDVGAVIATPEQLFAAYEDGFEQCDAGW 200
Qy 181 LADQTVRYPIRAPRVGCYGDKMGKAGVRTYGFRSPQETYDVYCYVDHLDGDVFHLTVPSK 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 201 LADQTVRYPIRAPRVGCYGDKMGKAGVRTYGFRSPQETYDVYCYVDHLDGDVFHLTVPSK 260
Qy 241 FTFEEAAKECENQDARLATVGELQAAWRNGFDQCDYGWLSDASVRHPVTVARAQCGGGLL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 261 FTFEEAAKECENQDARLATVGELQAAWRNGFDQCDYGWLSDASVRHPVTVARAQCGGGLL 320
Qy 301 GVRTLYRFENQTGFPPPDSRFDAYCFKPKEGNS 333
|||||||||||||||||||||||||||||| :
Db 321 GVRTLYRFENQTGFPPPDSRFDAYCFKPKEATT 353
Prosecution Insights