DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-13 and 24-33 are pending in the instant application.
Election/Restrictions
Applicant's election with traverse of Group I, (claims 1-13, 24-27 and 33) and the species of (a)(i) protein, (a)(ii) antibody/antigen-binding fragment against VEGF, (b)second component which comprises one hyaluronic acid binding protein (HABP) domain in the reply filed on 21 April 2026 is acknowledged. Applicant indicates that claims 1-10, 24-27 and 33 read on the elected species. However, claim 10 does not read on the second species election as the second component is either a CD44 domain or a TSG-6 domain. The traversal is on the ground(s) that claim 33 is directed to a therapeutic molecule and not a method and therefore, should be included in group I. Applicant’s assessment regarding claim 33 is correct and claim 33 will be examined with Group I. Applicant did not offer any further arguments regarding the propriety of the restriction.
The requirement is still deemed proper and is therefore made FINAL.
Claims 10-13 and 28-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 21 April 2026. Claims 1-9, 24-27 and 33 are under consideration in the instant Office action.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statements (IDS) submitted on 30 August 2023, 16 May 2025 and 30 December 2025 have been considered by the examiner.
Drawings
The drawings are objected for the following reasons:
The drawings do not comply with 37 CFR 1.84 (a)(1) as the drawings are not in black ink that secures solid black lines. The drawings appear to have various shades of gray, some of which results in lines which are not solid and text which is not solid, resulting in blurred text and fuzzy lines. See screenshots below:
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Figure 19 does not comply with 37 CFR 1.84(u)(1) which requires that partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. View numbers must be preceded by the abbreviation “FIG.”. Figure 19 spans 4 pages and is labeled as Figure 19 and “Figure 19 (cont.)”. Figure 19 should be labeled as Fig.19A, Fig. 19B, Fig. 19C and Fig. 19D in order to be compliant with 37 CFR 1.84.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Specifically: The specification refers to “(GxS)” which is an amino acid sequence of 4 or more amino acids. In some instances x=3 which makes the sequence GGGS and in other instances x=4 which makes the sequence GGGGS. Even though “(GxS)” is a shorthand for the amino acid sequence, it is, nonetheless, an amino acid sequence. Examples of this are found in paragraphs [00137] and [00139] as well as in claim 8. Each instance of “GxS” should include an appropriate sequence identifier.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The invention is defined by the claims and claim 1 does not require hyaluronan in the claimed molecule. The two components which are present are covalently bound. The title does not provide information which is clearly indicative of the invention to which the claims are directed.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract in the instant application is not composed of complete, grammatically correct sentences and is not in a narrative form. The first sentence begins with “a conjugate may comprise a first component….” which does not make clear what the invention of the instant application is directed to. Additionally, as a patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains and the invention is defined by the claims, the abstract should refer to targeting to the eye and not generically to “a tissue” as in line 7. Lastly, as the “invention” (as defined by the claims) specifically excludes domains of versican, the last line of the abstract appears to not be directed to the invention of the instant application.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The disclosure is objected to because of the following informalities:
The specification at [00175] is a description of Figure 19 and states that it “shows the alignment of VG1 variants SEQ ID NOs: 29, 33-59”. While these sequences may appear in the order that is recited, this is not necessarily clear as the sequence identifier has not been paired up with each of the sequences present in the Figure. If these sequences are in the order that they appear (from top to bottom), it is suggested that the term “respectively” follow the listing of the sequence identifiers or some other language be provided to make clear the association of the sequence identifier with the given sequence it represents.
The specification at [00199] states that the “term “or” is used in an inclusive sense, i.e., equivalent to “and/or,” unless the context clearly indicates otherwise”. This alteration of a basic word the indicates an alternative, a choice or an equivalent. This definition is objected to because it is not clear in what context “or” would actually mean “or” if the specification states that it means “and/or”.
Appropriate correction is required.
The instant application uses a number of trade names and/or marks used in commerce. When referenced in the specification, the terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
In the instant application, there are instances in which the trademarked term is properly capitalized and is accompanied by the generic terminology (see [00234] for example). However, there are instances in the instant application when the generic terminology is not provided (see [0054] and [00242], for example). The entire specification should be reviewed to make sure generic terminology accompanies all uses of trade names/marks as is required.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Interpretation
In the restriction requirement, mailed 21 January 2026, an election of a therapeutic molecule comprising (a) a first component capable of binding to a therapeutic target in the eye and (b) one or more second components capable of binding to hyaluronan. The restriction clearly indicated that “a single molecular embodiment of a species to be examined” was required.
Applicant elected as the first component a protein and further that the protein be “an antibody or antigen-binding fragment against VEGF”. This is not a single molecular embodiment for the first component. The election is one of a subgenus of molecules that bind to a therapeutic target in the eye.
Applicant elected as the second component capable of binding hyaluronan “Hyaluronic Acid Binding Protein (HABP) domain”. This election is problematic because the instant specification at [00188] defines “hyaluronic acid binding domain,” “hyaluronic acid binding moiety,” “HA binding domain or “HABD” as referring to any moiety that is capable of binding hyaluronic acid and that “the HABD may be a domain of a HA-binding protein”. The specification at [00266] “hyaluronan-binding protein or “HA-binding protein” refers to a protein or a family of proteins that bind HA and that these proteins comprise HABDs and that various HA-binding molecules are well-known in the art. In this paragraph, Hyaluronan binding protein 1 (HABP1; also known as C1qBP/C1qR and p32) is mentioned. From the disclosure of the specification, it is not clear what is encompassed by the election of 21 April 2026 (“Hyaluronic Acid Binding Protein (HABP) domain”). For the purposes of examination, this election is being construed as being directed to the hyaluronic acid binding domain of Hyaluronan binding protein 1 (HABP1), as this is the only single molecular embodiment which is called HABP and is also called a binding protein. Art will be applied accordingly.
Claim Objections
Claim 9 is objected to because of the following informalities: the claim includes numerous abbreviations which are not defined. Abbreviations should be defined upon their first usage in a claim for clarity purposes. Appropriate correction is required.
Claim 25 is objected to because of the following informalities: the claim recites “wherein the cysteine knot peptide is at least ….. identity with SEQ ID NO:92”. First, the claim is not grammatically correct (ie. identity would need to be identical for grammatical purposes). However, the claim is also not conceptually correct either because a cysteine knot peptide does not have identity with a sequence identifier but rather the amino acid sequence of the peptide would have identity with the amino acid sequence of SEQ ID NO:92. The claim is not indefinite, but it should be amended so that it is grammatically and conceptually correct for the elements/properties/characteristics which are being recited. 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 1-8 and 24-26, as well as dependent claims 9, 27 and 33, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 7 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 molecule may not always bind and therefore, the metes and bounds of the claims are unclear.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 recites the broad recitation “protein”, and the claim also recites “peptide”, “a receptor or fragment thereof”, and “ligand to a receptor” which are narrower statements of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 3 recites that the first component is chosen from an antibody, antigen-binding fragment, “particularly an antibody fragment, more particularly…”. The language of particularly, more particularly, especially, more especially in the claim renders the claim indefinite because it is not clear if these are required elements of the claim or merely exemplary embodiments. Therefore, the metes and bounds of the claim are unclear and indefinite.
Claim 4 recites “Hyaluronic Acid Binding Protein (HABP) domain”. As pointed out above in the “Claim Interpretation” section, this recitation is indefinite as the instant specification does not define “Hyaluronic Acid Binding Protein (HABP) domain” in a limiting manner. It is not clear if this recitation is intended to refer to HABP1, which is a binding protein for hyaluronic acid known in the art or if it is meant to be a genus of molecules or if it refers to a specific protein named HABP (which could not be identified in the prior art as HABP is used to mean Hyaluronan Binding Protein and refers to a specific type of protein; i.e. a genus of molecules with a particular function). Therefore, the metes and bounds of “Hyaluronic Acid Binding Protein (HABP) domain” are unclear and indefinite.
Claim 5 recites the limitation "the conjugate" in lines 1-2, referring back to claim 1. There is insufficient antecedent basis for this limitation in the claim. Claim 1 does not refer to a conjugate; reference to “therapeutic molecule” instead of “conjugate” would be remedial.
Claim 6 is indefinite because the claim is referring to the third component in claim 1 which is indicated to be optional. If claim 6 does not now require the third component, the limitations of claim 6 would not actually further limit the subject matter of claim 1 because if the option was not taken, the third component would not be present in the therapeutic molecule of claim 1. Claim 6 should make clear that the therapeutic compound of claim 1 comprises the third component.
Claim 6 is indefinite because of the limitation “wherein the hyaluronan” “provides a molar excess of binding equivalents to the one or two second components”. Claim 6 depends from claim 1, for which hyaluronan is optional. But it is also 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. Therefore, the metes and bounds of the claim cannot be determined.
Claim 8 is indefinite for the recitation “the first and the second components are comprised in a fusion protein”. This recitation is unclear because it appears to construe that there is a larger fusion protein which includes the first and second components within it. Alternatively, this recitation could just mean that the first and second components are proteins and they are joined together to constitute a fusion protein. Therefore, because there are alternative interpretations of the language, the metes and bounds of the claim are indefinite.
Claim 8 is also indefinite for the recitation that the one or two of the second components are covalently bound to the N-terminus and/or the C-terminus of the first component. If there is only one second component, it would not be possible for the second component to be bound to both the N-terminus and the C-terminus of the first component unless the structure is meant to be a circular protein, which seems unlikely. Therefore, the claim recitation is unclear because it does not make sense when only one second component is present.
Claim 8 is also indefinite for the recitation of “particularly” and “more particularly” as it is not clear if these are limitations of the claim or merely preferred embodiments and not limitations of the claim.
Claim 26 recites the limitation "the amino acid sequence" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 26 depends from claim 24 and claim 24 does not recite an amino acid sequence.
Dependent claims 9, 27 and 33 are indefinite as they depend from claims which are indefinite and do not resolve the issue for which the claim they depend from are indefinite.
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.
Claim 3 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 3 recites “wherein the first component is chosen from an antibody, antigen-binding fragment, particularly an antibody fragment”. The first component is recited n claim 1 as being capable of binding to a therapeutic target in the eye. However, the recitation of “antibody fragment” encompasses pieces of an antibody which do not necessarily bind to a target. The claim is not enabled for the full scope of “antibody fragment”. The claim is enabled for “antigen-binding fragment” as it would necessarily include structure which would bind to a target.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1-9, 27 and 33 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. PGPub 2017/0290876 A1 (Ghosh et al.).
Ghosh et al. teach long-acting proteins for ocular therapy (see [0001]). Molecules are taught which are “peptide tags” that bind to hyaluronic acid in the vitreous linked to a therapeutic molecule (note: hyaluronic acid and hyaluronan are used interchangeably and are known in the art to be the same thing). Linking the hyaluronic acid binding moiety (peptide tag) to the therapeutic molecule results in a longer ocular half-life, longer ocular retention and a longer duration of action of the therapeutic molecule when administered to the eye for the treatment of ocular diseases (see [0002]). Therefore, Ghosh et al. teach a peptide tag that binds hyaluronan (HA) with a KD of less than or equal to 9.0 µM at [0004] (see instant claim 7). Ghosh et al. further teach that the peptide tag (HA binding protein) is linked to a protein at either terminus, wherein the protein is therapeutic protein, an antibody or antigen binding fragment and wherein the peptide tagged molecule binds to VEGF (see [0005]-[0007]). Therefore, Ghosh et al. teach a therapeutic molecule comprising a first component capable of binding to a therapeutic target in the eye (antibody which binds VEGF) and a second component capable of binding to hyaluronan (peptide tag) (see claims 1-5, 8-9).
Ghosh et al. teaches compositions comprising the peptide tag and peptide tagged molecules wherein the composition comprises a pharmaceutically acceptable excipient, diluent or carrier (see [0012]; see instant claim 27). Ghosh et al. also teach that the peptide tag is one that binds to hyaluronan (HA) and that HA binding proteins are known in the art and include versican, CD44, RHAMM, Aggrecan, bacterial HA synthase, collagen VI and TSG-6 (see [0046]). Ghosh et al. teaches at least 27 embodiments of a HA binding protein fused to an anti-VEGF antibody, including 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 (see Table 3, pages 56-58) (see instant claim 33). Therefore, Ghosh et al. anticipate the instant claims.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1 and 24-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. PGPub 2017/0290876 A1 (Ghosh et al.) in view of U.S. Pat. No. 10,428,125 (Hannoush et al.).
The teachings of Ghosh et al. are as provided above. While Ghosh et al. teaches a therapeutic molecule of claim 1 (comprising a hyaluronan binding domain covalently bound to a component capable of binding to a therapeutic target in the eye), Ghosh et al. do not teach that a therapeutic molecule further comprising a cysteine knot peptide.
Hannoush et al. teach a non-naturally occurring cystine knot peptide that binds to VEGF-A and inhibits VEGF-A activity (see column 18, lines 49-55), including a peptide having the amino acid sequence of SEQ ID NO:142 (see claim 2 of Hannoush et al.), which is identical to that of SEQ ID NO:92 of the instant claim 25. Hannoush et al. teach that the cystine knot peptides bind to VEGF-A and have the ability to increase thermal stability of proteins and enzymes (see column 1, lines 35-45) and that the non-naturally occurring cystine knot peptides disclosed can be used for treating ocular diseases and/or disorders resulting from abnormal angiogeneisis and/or abnormal vascular permeability (see column 19, lines 1-8). Hannoush et al. also teach that the cystine knot peptide can be fused with a second moiety (such as a protein) make a chimeric molecule such as to a targeting moiety for delivery to various tissues as well as to therapeutic moieties (see column 79, lines 56-65; column 82, line 63 to column 83, line 29; column 84, lines 1-9).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include the cystine knot peptide of Hannoush et al. (SEQ ID NO: 142) in the construct of Ghosh et al., fused to the therapeutic peptide element of Ghosh et al., because Hannosh et al. teach that this is an appropriate and contemplated use of the cystine knot peptides. One of ordinary skill in the art would have been motivated to combine the cystine knot peptide of Hannoush et al. in the construct of Ghosh et al. because Hannosh et al. teach that the cystine knot peptide inhibits VEGF-A and that it also can be used to treat ocular disorders, which is the same purpose as the construct of Ghosh et al. One would have had a reasonable expectation of success in combining the cystine knot peptide of Hannoush et al. with the construct of Ghosh et al. because the creation of fusion proteins with multiple actions/specificities is well-known in the art as evidenced by the teachings of Hannoush et al. (which specifically teach making fusions with the cystine knot peptides). Therefore, the invention as a whole would have been prima facie obvious over the teachings of Ghosh et al. and Hannosh et al., absent evidence to the contrary.
Claim(s) 1, 24 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. PGPub 2017/0290876 A1 (Ghosh et al.) in view of Jiang et al. US PGPub 2013/0202583 (Jiang et al.).
The teachings of Ghosh et al. are as provided above. While Ghosh et al. teaches a therapeutic molecule of claim 1 (comprising a hyaluronan binding domain covalently bound to a component capable of binding to a therapeutic target in the eye), Ghosh et al. do not teach that a therapeutic molecule further comprising a cysteine knot peptide.
Jiang et al. teach Versican as a hyaluronan binding protein (HABP) that contains two or more link modules (see [0015]). Jiang teach a versican molecule that has 98.8% sequence identity to SEQ ID NO:94 of the instant application (see [0233]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include the hyaluronan binding protein (HABP) Jiang et al. (SEQ ID NO: 235) in the construct of Ghosh et al., fused to the therapeutic peptide element of Ghosh et al., because Jiang et al. teach that this protein is a hyaluronan binding protein and the constructs of Ghosh et al. include a hyaluronan binding protein. One of ordinary skill in the art would have been motivated to combine the hyaluronan binding protein of Jiang et al. in the construct of Ghosh et al. because Ghosh et al. teach a construct of a hyaluronan binding protein and a therapeutic peptide. One would have had a reasonable expectation of success in combining the HABP of Jiang et al. with the construct of Ghosh et al. because the creation of fusion proteins is well-known in the art as evidenced by the teachings of either Ghosh et al. or Jiang et al. Therefore, the invention as a whole would have been prima facie obvious over the combined teachings, absent evidence to the contrary.
Claim(s) 1-9, 27 and 33 is/are rejected 35 U.S.C. 103 as being unpatentable over U.S. PGPub 2017/0290876 A1 (Ghosh et al.) in view of Saha et al. (Multi-functional, multicompartmental hyaluronan-binding protein 1 (HABP1/p32/gC1qR): implication in cancer progression and metastasis. Oncotarget, Vol. 9(No. 12): 10784-10807, 2018).
The teachings of Ghosh et al. are as provided above. While Ghosh et al. teaches a therapeutic molecule of claim 1 (comprising a hyaluronan binding domain covalently bound to a component capable of binding to a therapeutic target in the eye), Ghosh et al. do not teach that the hyaluronan binding domain is a hyaluronic acid binding protein domain.
Saha et al. teach hyaluronan-binding protein 1 (HABP1) which is a binding protein for hyaluronan and is a member of a family of proteins called “hyaladherins” which possess a common protein motif (link protein B-(X)7-B) (see page 10784, column 2). Saha et al. also teach at page 10785, column 2, last paragraph, that the hyaluronan binding motif in HABP1 is found at amino acids 119-128.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the HABP1 of Saha et al. for the peptide tag of Ghosh et al. because Ghosh et al. teach that the peptide tag is a hyaluronan binding peptide. One would have a reasonable expectation of making the substitution because the HABP1 of Saha et al. contains the protein motif of hyaladherins and binds to hyaluronan and therefore, would perform the same function as the other hyaluronan binding proteins used by Ghosh et al. One of ordinary skill in the art would be motivated to make the substitution because HABP1 is a binding protein for hyaluronan and therefore, would be expected to function as such for the purposes of construct taught by Ghosh et al.
Claim(s) 1 and 24-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. PGPub 2017/0290876 A1 (Ghosh et al.) in view of U.S. Pat. No. 10,428,125 (Hannoush et al.) and Saha et al..
The teachings of Ghosh et al. are as provided above. While Ghosh et al. teaches a therapeutic molecule of claim 1 (comprising a hyaluronan binding domain covalently bound to a component capable of binding to a therapeutic target in the eye), Ghosh et al. do not teach that a therapeutic molecule further comprising a cysteine knot peptide.
Saha et al. teach hyaluronan-binding protein 1 (HABP1) which is a binding protein for hyaluronan and is a member of a family of proteins called “hyaladherins” which possess a common protein motif (link protein B-(X)7-B) (see page 10784, column 2). Saha et al. also teach at page 10785, column 2, last paragraph, that the hyaluronan binding motif in HABP1 is found at amino acids 119-128.
Hannoush et al. teach a non-naturally occurring cystine knot peptide that binds to VEGF-A and inhibits VEGF-A activity (see column 18, lines 49-55), including a peptide having the amino acid sequence of SEQ ID NO:142 (see claim 2 of Hannoush et al.), which is identical to that of SEQ ID NO:92 of the instant claim 25. Hannoush et al. teach that the cystine knot peptides bind to VEGF-A and have the ability to increase thermal stability of proteins and enzymes (see column 1, lines 35-45) and that the non-naturally occurring cystine knot peptides disclosed can be used for treating ocular diseases and/or disorders resulting from abnormal angiogeneisis and/or abnormal vascular permeability (see column 19, lines 1-8). Hannoush et al. also teach that the cystine knot peptide can be fused with a second moiety (such as a protein) make a chimeric molecule such as to a targeting moiety for delivery to various tissues as well as to therapeutic moieties (see column 79, lines 56-65; column 82, line 63 to column 83, line 29; column 84, lines 1-9).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the HABP1 of Saha et al. for the peptide tag of Ghosh et al. because Ghosh et al. teach that the peptide tag is a hyaluronan binding peptide and additionally to include the cystine knot peptide of Hannoush et al. (SEQ ID NO: 142) in the construct of Ghosh et al., fused to the therapeutic peptide element of Ghosh et al., because Hannosh et al. teach that this is an appropriate and contemplated use of the cystine knot peptides. One would have a reasonable expectation of making the substitution because the HABP1 of Saha et al. contains the protein motif of hyaladherins and binds to hyaluronan and therefore, would perform the same function as the other hyaluronan binding proteins used by Ghosh et al. One of ordinary skill in the art would be motivated to make the substitution because HABP1 is a binding protein for hyaluronan and therefore, would be expected to function as such for the purposes of construct taught by Ghosh et al. One of ordinary skill in the art would also have been motivated to combine the cystine knot peptide of Hannoush et al. in the construct of Ghosh et al. because Hannosh et al. teach that the cystine knot peptide inhibits VEGF-A and that it also can be used to treat ocular disorders, which is the same purpose as the construct of Ghosh et al. One would have had a reasonable expectation of success in combining the cystine knot peptide of Hannoush et al. with the construct of Ghosh et al. because the creation of fusion proteins with multiple actions/specificities is well-known in the art as evidenced by the teachings of Hannoush et al. (which specifically teach making fusions with the cystine knot peptides). Therefore, the invention as a whole would have been prima facie obvious over the combined teachings, absent evidence to the contrary.
Claim(s) 1, 24 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. PGPub 2017/0290876 A1 (Ghosh et al.) in view of Jiang et al. US PGPub 2013/0202583 (Jiang et al.) and Saha et al..
The teachings of Ghosh et al. are as provided above. While Ghosh et al. teaches a therapeutic molecule of claim 1 (comprising a hyaluronan binding domain covalently bound to a component capable of binding to a therapeutic target in the eye), Ghosh et al. do not teach that a therapeutic molecule further comprising a cysteine knot peptide.
Saha et al. teach hyaluronan-binding protein 1 (HABP1) which is a binding protein for hyaluronan and is a member of a family of proteins called “hyaladherins” which possess a common protein motif (link protein B-(X)7-B) (see page 10784, column 2). Saha et al. also teach at page 10785, column 2, last paragraph, that the hyaluronan binding motif in HABP1 is found at amino acids 119-128.
Jiang et al. teach Versican as a hyaluronan binding protein (HABP) that contains two or more link modules (see [0015]). Jiang teach a versican molecule that has 98.8% sequence identity to SEQ ID NO:94 of the instant application (see [0233]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the HABP1 of Saha et al. for the peptide tag of Ghosh et al. because Ghosh et al. teach that the peptide tag is a hyaluronan binding peptide. One would have a reasonable expectation of making the substitution because the HABP1 of Saha et al. contains the protein motif of hyaladherins and binds to hyaluronan and therefore, would perform the same function as the other hyaluronan binding proteins used by Ghosh et al. Additionally, it would have been obvious to attach a second hyaluronan binding protein (HABP) Jiang et al. (SEQ ID NO: 235) in the construct of Ghosh et al., fused to the therapeutic peptide element of Ghosh et al., because Jiang et al. teach that this protein is a hyaluronan binding protein and the constructs of Ghosh et al. include a hyaluronan binding protein. One of ordinary skill in the art would have been motivated to combine the hyaluronan binding protein of Jiang et al. in the construct of Ghosh et al. because Ghosh et al. teach a construct of a hyaluronan binding protein and a therapeutic peptide. One of ordinary skill in the art would have been motivated to modify the peptide tag of Ghosh et al. by including the hyaluronan binding proteins of Jiang and Saha because it would create another construct that has the ability to bind to hyaluronan and would be useful in the treatment of ocular conditions. Furthermore, the hyaluronan binding protein of Jiang et al. is also a cystine knot protein, which binds to VEGF-A and therefore, is additionally therapeutic in the eye. One would have had a reasonable expectation of success in combining the HABP’s of Jiang et al. and Saha et al. with the construct of Ghosh et al. because the creation of fusion proteins is well-known in the art as evidenced by the teachings of either Ghosh et al. or Jiang et al. Therefore, the invention as a whole would have been prima facie obvious over the combined teachings, absent evidence to the contrary.
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 1-9 and 24, 26 and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 29-34, 38, 52 and 54 of copending Application No. 18/301,180.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims encompass common embodiments. The claims of both applications are directed to therapeutic molecules which comprise a therapeutically active agent (or first component) and a hyaluronan-binding domain (claim 1 of both applications). The instant application limits the therapeutic molecule first component to a protein (see claim 2) and an antibody (see claim 3) and wherein the first component binds to a therapeutic target in the eye (claim 1) and wherein the target is VEGF. Claims 1, 29, 30-34 and 38 of ‘180 include all of these same limitations. Claims 52 and 54 of ‘130 correspond to instant claims 24 and 26. While ‘130 does not specifically recite a pharmaceutical composition, instant claim 27 would be obvious over the claims of ‘130 which are directed to a “therapeutic molecule” because one of ordinary skill in the art would necessarily include a molecule which is therapeutic and meant to be administered to a subject in a pharmaceutical composition. Therefore, the instant claims are not patentably distinct from those of ‘180.
This is a provisional nonstatutory double patenting rejection.
Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Suto et al. Essential hyaluronan structure for binding with hyaluronan-binding protein (HABP) determined by glycotechnological approach. Cabohydrate Polymers 251: 116989. 2021.
Toole. Hyaluronan and its binding proteins, the hyaladherins. Current Opinion in Cell Biology. 2: 839-844, 1990.
Day et al. Hyaluronan-binding Proteins: Tying up the Giant. J. Biol. Chem. 277(7): 4585-4588, 2002.
Deb et al. Molecular Cloning of Human Fibroblast Hyaluronic Acid-binding Protein Confirms Its Identity with P-32, a Protein Co-purified with Splicing Factor SF2. J. Biol. Chem. 271(4): 2206-2212, 1996.
Conclusion
No claim is allowed.
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/Christine J Saoud/Primary Examiner, Art Unit 1645
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