Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group II (i.e., claims 90-109 drawn to method for regenerating tissue in a subject by administering to the subject a peptide comprising a growth factor binding domain having an amino acid sequence that is at least 80% identical to one of SEQ ID NOs: 1-7, 13-15, 49-50, or 66-70, or a fragment thereof, wherein the peptide is less than 100 amino acids in length) in the reply filed on December 19, 2025, is acknowledged.
Additionally, Applicant’s election of Species A (i.e., a single and specific peptide as a fusion of SEQ ID NO: 1 with SEQ ID NO: 64 (note: a growth factor binding domain fused to a collagen binding peptide)) in the reply filed on December 19, 2025, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Please note that the election of SEQ ID NO: 1 as a single and specific peptide comprising a growth factor binding domain is unclear as further discussed in the 112(b) rejection below given that there are two different sequences (i.e., no overlap) identified as SEQ ID NO: 1 (i.e., Sequence Listing amino acid sequence and the specification at [0081] and Table 1). In order to advance prosecution, the Examiner is examining SEQ ID NO: 2 as the peptide comprising a growth factor binding domain. Once a single amino acid sequence for SEQ ID NO: 1 has been identified, examination of that sequence will be performed.
Also please note that Species A is expanded to include where the peptide is attached to a tag as recited in instant claims 97 and 107 in light of the Examiner’s search. Further, it is noted that elected SEQ ID NO: 64 as the collagen binding peptide is free of the art, and thus, the species of collagen binding peptide is expanded as discussed below. The closest prior art is WO 2016/016269 A1. ‘269 teaches an anti-collagen antibody containing HCDR1-3 and LCDR1-3 represented as SEQ ID NOs: 3-8, respectively, or SEQ ID NOs: 11-12, 5, and 14-16, respectively (See ‘269, pg. 3, last paragraph to pg. 4, 1st paragraph). Moreover, ‘269 teaches a VL and VH chain amino acid sequences that are 100% identical to instant SEQ ID NOs: 63 and 65, respectively (See ‘269, SEQ ID NOs: 1-2). However, ‘269 does not teach or suggest an amino acid sequence that is 100% identical to instant SEQ ID NO: 64. Thus, when the peptide fragment is instant SEQ ID NO: 64, the claimed invention is free of the prior art.
Status of Claims
Claims 1-89 were originally filed on July 13, 2023.
The amendment received on November 28, 2023, canceled claims 3, 5-11, 14-15, 17-24, 26-32, 35-36, 38-42, 44-46, 48-53, 55-56, 58-66, 68, 71-81, and 83-87; and amended claims 4, 12, 16, 25, 33-34, 37, 43, 47, 54, 57, 67, 69-70, and 82. The amendment received on December 19, 2025, canceled claims 1-89; and added claims 90-109.
Claims 90-109 are currently pending and claims 90, 93-94, 97, 99-100, 103-104, 107 and 109 are under consideration as claims 91-92, 95-96, 98, 101-102, 105-106, and 108 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 19, 2025.
Priority
The present application is a continuation of US Application No. 15/733,085, filed May 13, 2020, now issued as US Patent No. 11,732,029, which claims status as a 371 (National Stage) of PCT/US2018/060760 filed November 13, 2018, and claims priority under 119(e) to U.S. Provisional Application Nos. 62/585,101 filed on November 13, 2017, and 62/758,845 filed on November 12, 2018.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 29, 2023 is being considered by the examiner.
Sequence Interpretation
Please note that the Examiner is interpreting the scope of claims 90 and 100 as open-ended requiring at least 80% identity to elected SEQ ID NO: 2 thereby encompassing up to 4 amino acid differences from SEQ ID NO: 2. Moreover, the peptide being at least 80% identical to elected SEQ ID NO: 2 can have any N-/C-terminal additions up to 300 amino acids in length. Moreover, it is noted that a fragment of SEQ ID NO: 2 encompasses any size fragment ranging from any dipeptide (i.e., any two contiguous amino acid residues) to a fragment with one deleted amino acid at the N- or C-terminus of SEQ ID NO: 2.
For claims 93 and 103, it is noted that the claims are directed to any peptide that exhibits the function of collagen binding. It is further noted that the instant specification does not define what constitutes a peptide that exhibits the function of collagen binding. However, the instant specification teaches several species that constitute a collagen binding peptide. For example, a peptide that binds collagen comprises the A3 domain of vWF, i.e., SEQ ID NO: 47, a decorin polypeptide, i.e., SEQ ID NO: 48, and one or more CDRs from an anti-collagen antibody, i.e., a Fab antigen-binding fragment referred to as FabCol and depicted as SEQ ID NOs: 62-65 (See instant, [0013]-[0015], [0084], [0210], [0224]-[0227]).
Additionally, the art recognizes a number of peptides that exhibit collagen binding. Abd-Elgaliel et al. teaches specific peptide sequences in Figure 1 (See Abd-Elgaliel et al., Biopolymers 100:167-173 (2013) at Figure 1). These peptides include linear and cyclic peptides (See Abd-Elgaliel, Figure 1). The peptides that contain a C-terminal unnatural biphenylalanine residue demonstrated a modest contribution to collagen binding (See Abd-Elgaliel, pg. 6, last paragraph). Although, the peptide sequences with a C-terminal unnatural biphenylalanine residue exhibited improved collagen binding, the peptide sequences without a C-terminal unnatural biphenylalanine residue exhibited collagen binding, albeit, reduced compared to the sequences with a C-terminal unnatural biphenylalanine residue (See Abd-Elgaliel, pg. 5, 5th paragraph). Thus, Abd-Elgaliel et al. concludes that the C-terminal unnatural Bip residue, rather than the peptide sequence or conformational restrain, dominated the collagen I binding (See Abd-Elgaliel, abstract). Moreover, Boone et al. teaches a hydropathy-based free energy estimation tool which allows quick evaluation of peptides binding to collagen (See Boone et al., Appl. Sci. 13:3342 (2023) at abstract). Boon et al. teaches several collagen-binding peptides, i.e., human collagen type I alpha chain 2 sense peptide (TKKTLRT), decorin LRR-10 (LRELHLNNN), mouse collagen type I alpha chain 2 sense peptide (SSNTLRS), fibroblast collagenase sequence (SQNPVQP), and KELNLVY for binding to collagen type III (See Boone, abstract; pg. 16, 1st paragraph; pg. 17, 3rd paragraph). Plus, WO 00/49159 A1 teaches a peptide fragment from fibronectin that binds to collagen, which ranges from Ala260 to Trp599 of fibronectin (See ‘159, pg. 15, last paragraph; pg. 26, 1st paragraph to pg. 27, 3rd paragraph). ‘159 also defines a fibronectin collagen binding domain as a collagen/gelatin-binding polypeptide from FN which is located between the position about 28 kDa from the amino terminal of FN to the position about 75 kDa from the amino terminal of FN (See ‘159, pg. 25, 4th paragraph). Therefore, given the discussion in the instant specification in combination with the pre-existing knowledge in the art regarding peptides that exhibit collagen binding, an ordinary skilled artisan would have put one in possession of the claimed genus of collagen binding peptides.
For claims 94 and 104, it is noted that the instant specification does not define what constitutes a collagen-binding fragment from an anti-collagen antibody or derived from an anti-collagen antibody. As such, the peptide fragment encompasses any peptide fragment derived from an anti-collagen antibody. As further discussed below in the 112(a) rejection, the species taught in the instant specification in combination with the state of the art, do not demonstrate possession of either a core sequence derived from an anti-collagen antibody for an ordinary skilled artisan to have put one in possession of the claimed genus.
Claim Objections
Claims 90 and 100 are objected to because of the following informalities: the claims recite, “SEQ ID NOS:1-7….” It is respectfully requested that the claims recite, “SEQ ID NOs: 1-7….” in order to be grammatically correct and to be in accordance with MPEP 2422. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 90, 93-94, 97, 99-100, 103-104, 107, and 109 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claims 90 and 100 include a “fragment of SEQ ID NO: 2”. The interpretation of this phrase is described above in the “Sequence Interpretation” section where a fragment of SEQ ID NO: 2 encompasses any size fragment ranging from any dipeptide (i.e., any two contiguous amino acids) to a peptide fragment with a one deleted amino acid at the N- or C-terminus. In addition to certain structural requirements, the fragment must also have “the function of SEQ ID NO: 2”. The “function” claimed for this fragment is to bind to a growth factor (i.e., function as a growth factor binding domain) in order to regenerate tissue/facilitate wound healing, and thus, in light of the specification, this is clearly the function to which the claim refers.
There is no conserved structure for a fragment of SEQ ID NO: 2. The prior art examined essential amino acid residues necessary for a peptide fragment of SEQ ID NO: 2 to exhibit adhesion activity, e.g., see WO 2006/025646 A1 at p. 11, examining the adhesion activity of a fragment of instant SEQ ID NO: 2 (i.e., SEQ ID NO: 1) including one or more deletions of an amino acid at the N- and/or C-terminus where a fragment having the two N-terminal proline deleted and the C-terminal arginine exhibited reduced adhesion activity compared to the non-fragment. However, this data fails to establish essential amino acid residues necessary for a fragment of SEQ ID NO: 2 to exhibit the claimed function. Moreover, the fragments of instant SEQ ID NO: 2 described in ‘646 fail to constitute a representative number of SEQ ID NO: 2 fragments. Thus, the claims are directed to peptide fragments with a certain function but no correlated structure associated with that function. Without such structure, the specification does not convey possession of the breadth of the claimed genus.
Alternatively, the written description requirement may be met by provided a representative number of species of the genus. In this, the specification does not provide any examples of a peptide fragment meeting the claimed limitations. Rather, the specification demonstrates that SEQ ID NO: 2 (i.e., alpha32932-2951) binds to growth factors such as VEGF-A165, PDGF-BB, PIGF, and FGF-2 as depicted in Figures 4C-F (See instant specification, paragraph [0159]). However, there is no indication of a necessary core structure or sequence for a peptide fragment of SEQ ID NO: 2 that would function similar to the full length sequences. Thus, this is not sufficient for the skilled artisan to envisage which fragments of SEQ ID NO: 2 preserve function.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “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, what 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 polypeptides which preserve the required function, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. 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, claims 90, 93-94, 99-100, 103-104, and 109 do not meet the written description requirement.
Claims 94 and 104 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Dependent claims 94 and 104 include a “peptide fragment” that exhibits the function of binding collagen and being from an anti-collagen antibody or derived from an anti-collagen antibody. The instant specification teaches that the collagen binding peptide can comprise one or more CDRs from an anti-collagen antibody where the one or more CDRs are derived from the light or heavy variable regions of an anti-collagen antibody (See instant, [0014]). However, the scope of claims 94 and 104 do not require any specific peptide fragment from or derived from an anti-collagen antibody. As such, structurally speaking, the peptide fragment encompassed by claims 94 and 104 include an enormous array of distinct peptide fragments ranging from any dipeptide to a fragment with one deleted residue at the N- or C-terminus of an anti-collagen antibody. In addition to certain structural requirements, as discussed supra, the fragment must also exhibit the function of collagen binding. The “function” claimed for this fragment is to bind to a collagen (i.e., function as collagen binding peptide) in order to regenerate tissue/facilitate wound healing, and thus, in light of the specification, this is clearly the function to which the claim refers.
The written description requirement may be met by provided a representative number of species of the genus and/or in light of the state of the art. With regard to the state of the art, WO 2016/016269 A1 teaches an anti-collagen antibody containing HCDR1-3 and LCDR1-3 represented as SEQ ID NOs: 3-8, respectively, or SEQ ID NOs: 11-12, 5, and 14-16, respectively (See ‘269, pg. 3, last paragraph to pg. 4, 1st paragraph). However, specific CDR sequences do not constitute either a core sequence that each peptide fragment from or derived from an anti-collagen antibody contains in order for the peptide fragment to bind to collagen, or a representative number of peptide fragments from or derived from an anti-collagen antibody. Thus, the claims are directed to peptide fragments with a certain function but no correlated structure associated with that function. Without such structure, the specification does not convey possession of the breadth of the claimed genus.
Alternatively, the written description requirement may be met by provided a representative number of species of the genus. In this, the specification teaches sequences of the variable regions of FabCol, which were taken from ‘269 (clone C11), and depicted as SEQ ID NOs: 62-65 (See instant, [0211]). However, these specific sequences do not constitute either a core sequence that each peptide fragment from or derived from an anti-collagen antibody contains in order for the peptide fragment to bind to collagen, or a representative number of peptide fragments from or derived from an anti-collagen antibody. Thus, this is not sufficient for the skilled artisan to envisage which fragments from or derived from an anti-collagen antibody preserve function.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “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, what 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 polypeptides which preserve the required function, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. 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, claims 94 and 104 do not meet the written description requirement.
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 90, 93-94, 97, 99-100, 103-104, 107, and 109 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. Instant claims 90 and 100 are directed to administering a peptide comprising a growth factor binding domain having an amino acid sequence that is at least 80% identical to SEQ ID NO: 1 (note: discussion limited to elected peptide species). However, the amino acid sequence depicted as SEQ ID NO: 1 in the Sequence Listing is different than the amino acid sequence depicted as SEQ ID NO: 1 in the paragraph [0081] in the instant specification. As such, it is unclear which amino acid sequence is be considered as SEQ ID NO: 1. Therefore, an ordinary skilled artisan would be unable to ascertain the metes and bounds of the presently claimed invention with respect to the amino acid sequence of SEQ ID NO: 1.
Please note that the Examiner will examine SEQ ID NO: 2 as the peptide comprising a growth factor binding domain in order to advance prosecution given that it is not clear which sequence should constitute SEQ ID NO: 1 (See “Election/Restriction” section for further details). Also please note that claims 93-94, 99, 103-104, and 109 are rejected by virtue of their dependency on claims 90 and 100.
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.
Claims 90, 97, 99-100, 107, and 109 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim WO Publication No. 2006/025646 A1 published on March 9, 2006 (cited in the IDS received on 11/29/23).
For claims 90 and 100, with respect to a method for regenerating tissue in a subject by administering to the subject a peptide having an amino acid sequence that is at least 80% identical to instant SEQ ID NO: 2 or a fragment thereof wherein the peptide is less than 300 amino acids in length as recited in instant claim 90; and with respect to a method for facilitating wound or tissue healing in a subject by administering to the subject a peptide having an amino acid sequence that is at least 80% identical to instant SEQ ID NO: 2 or a fragment thereof wherein the peptide is less than 300 amino acids in length as recited in instant claim 100:
Kim discloses the five LG domains of laminin-5 alpha3 chain (See Kim specification, pg. 20, 1st paragraph). The five LG domains are LG1, LG2, LG3, LG4, and LG5 where LG3 spans residues 1128-1364 of SEQ ID NO: 2 (See Kim specification, pg. 9, 1st paragraph; pg. 22, 1st paragraph). Resides 1312-1331 of the LG3 domain is 100% identical to instant SEQ ID NO: 2. Although Kim does not depict each LG domain as an individual sequence identifier, Kim analyzed each LG domain individually (See Kim specification, pg. 20, 1st paragraph; pg. 23, 1st paragraph). As such, the total length of the LG3 domain (i.e., 236 amino acids) constitutes a peptide with a length less than 300 amino acids. Further, Kim discloses a specific fragment peptides of instant SEQ ID NO: 2 (i.e., P4 peptide spanning residues 1312-1323 and represented as SEQ ID NO: 1 and P5 peptide spanning residues 1321-1332) (See Kim specification, pg. 10, 1st paragraph; pg. 24, 1st paragraph; pg. 25, 2nd paragraph) thereby constituting two specific fragments of instant SEQ ID NO: 2. Therefore, the LG3 domain constitutes a peptide having an amino acid sequence that is at least 80% identical to instant SEQ ID NO: 2 or a fragment thereof wherein the peptide is less than 300 amino acids in length as recited in instant claims 90 and 100.
Furthermore, Kim found that only the LG3 domain, which contains instant SEQ ID NO: 2, exhibited adhesive activity as depicted in Figures 2A-C (See Kim specification, pg. 23, 1st paragraph; Figures 2A-C). Kim also found that only the LG3 domain protein resulted in cell spreading activity (See Kim specification, pg. 23, 3rd paragraph). Thus, Kim found that a peptide comprising instant SEQ ID NO: 2 that is less than 300 amino acids in length supports cell adhesion and spreading (See Kim specification, pg. 23, 3rd paragraph). Plus, Kim found that SEQ ID NO: 1 (i.e., a fragment of instant SEQ ID NO: 2 as the P4 peptide) showed a strong dose-dependent cell adhesion activity at concentration greater or equal to 10 mcg/well whereas the P5 peptide showed a very weak dose-dependent adhesion activity at concentrations greater or equal to 25 mcg/well (See Kim specification, pg. 25, 3rd paragraph). Kim also performed rat experiments (note: rats constitute the instant subject) in Example 8 where two full-thickness rectangular wounds of 1 cm x 1 cm were prepared on the back of each rat (See Kim specification, pg. 35, 2nd paragraph). Then a peptide P4 (i.e., a fragment of instant SEQ ID NO: 2)-coated Beschitin W microfiber was applied to the wounds of each rat (See Kim specification, pg. 35, 2nd paragraph) thereby constituting administering to a subject a peptide fragment of instant SEQ ID NO: 2 as recited in instant claims 90 and 100. The wounds were then examined for epithelialization and granulation (See Kim specification, pg. 35, 2nd paragraph). Kim found that the rat wounds treated with the peptide P4 microfiber had no surface tissue debris and there was remarkable proliferation of young capillaries and fibroblasts (See Kim specification, pg. 35, last paragraph). Epithelialization of the wound was complete after 4 weeks, inflammatory cells disappeared, and connective tissue was densely formed (See Kim specification, pg. 36, 1st paragraph). The results of this animal experiment demonstrates that early-stage healing in the peptide P4 microfiber group was faster than that in the control group (See Kim specification, pg. 36, 2nd paragraph). Thus, the rat experiment constitutes a method for regenerating tissue, facilitating wound or tissue healing in a subject by administering to the subject a peptide fragment of instant SEQ ID NO: 2 and where the peptide is less than 300 amino acids in length as recited in instant claims 90 and 100.
For claims 90 and 100, with respect to where the amino acid sequence is a growth factor binding domain:
As discussed supra, Kim discloses administering a peptide comprising an amino acid sequence that is at least 80% identical to instant SEQ ID NO: 2 or a fragment of SEQ ID NO: 2 and is less than 300 amino acids in length to a subject. As such, Kim satisfies the structural claim limitations and the claimed manipulative step as recited in instant claims 90 and 100. Pursuant under MPEP 2112, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). Thus, Kim’s LG3 domain or LG3 domain fragment inherently function as a growth factor binding domain. Therefore, the disclosure of Kim satisfies the claim limitation with respect to where the amino acid sequence is a growth factor binding domain as recited in instant claims 90 and 100.
For claims 97, 99, 107, and 109, with respect to where the peptide is attached to a tag or a functional moiety as recited in instant claims 97 and 107; and with respect where the peptide is comprised in a molecular complex as recited in instant claims 99 and 109:
Kim discloses that the recombinant LG domain amino acid sequences (i.e., LG1-5 domains) are expressed in the form of fusion proteins bound with six histidine tags in the C-terminal as a detecting probe to facilitate their purification (See Kim specification, pg. 9, 1st paragraph) thereby constituting where the six histidine tags are a tag as recited in instant claims 97 and 107. It is noted that the instantly claimed molecular complex is not defined in the instant specification, and thus, encompasses any type of interaction, e.g., covalent or noncovalent. Pursuant to MPEP 2131.02, it states that, “[i]f one of ordinary skill in the art is able to "at once envisage" the specific compound within the generic chemical formula, the compound is anticipated. One of ordinary skill in the art must be able to draw the structural formula or write the name of each of the compounds included in the generic formula before any of the compounds can be "at once envisaged." One may look to the preferred embodiments to determine which compounds can be anticipated.” In re Petering, 301 F.2d 676, 133 USPQ 275 (CCPA 1962). Thus, given that there are only five LG domains, an ordinary skilled artisan would clearly envisage six histidine tags bound to the LG3 amino acid sequence thereby constituting where the peptide is comprised in a molecular complex. Therefore, the disclosure of Kim satisfies the claim limitation as recited in instant claims 97, 99, 107, and 109.
For claims 99 and 109, with respect to where the peptide is comprised in a biomaterial scaffold:
Kim discloses wound coverings and scaffold for tissue engineering including a peptide having an amino acid sequence of SEQ ID NO: 1 in human laminin-5 alpha3 recombinant LG3 domain, fragments, or derivatives thereof (See Kim specification, pg. 14, last paragraph to pg. 15, 1st paragraph). The scaffolds include porous scaffolds prepared by synthetic biodegradable high molecular compounds such as poly amino acids, chitosan, and collagen (See Kim specification, pg. 15, last paragraph to pg. 16, 1st paragraph) thereby constituting a biomaterial scaffold. Moreover, as discussed supra for claims 90 and 100, Kim also discloses a specific embodiment in Example 8-1 and 8-2, Kim discloses a peptide P4-coated Beschitin W microfiber (i.e., peptide P4 spans residues 1312-1323 of the LG3 domain) (See Kim specification, pg. 35, 2nd paragraph). Therefore, the disclosure of Kim satisfies the claim limitation as recited in instant claims 99 and 109.
Therefore, the disclosure of Kim anticipates instant claims 90, 97, 99-100, 107, and 109.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 90, 93, 100, and 103 are rejected under 35 U.S.C. 103 as being unpatentable over Kim WO Publication No. 2006/025646 A1 published on March 9, 2006 (cited in the IDS received on 11/29/23), as applied to claims 90 and 100 above, and in view of Briquez et al., Adv. Wound Care 4:479-489 (2015) (cited in the IDS received on 11/29/23), as applied to claims 93 and 103 herewith.
For claims 90 and 100, please see discussion of Kim above.
For claims 93-94 and 103-104, with respect to where the peptide is attached to a collagen binding peptide as recited in instant claims 93 and 103; and with respect to where the collagen binding peptide comprises a collagen-binding fragment from an anti-collagen antibody or a collagen-binding fragment derived from an anti-collagen antibody as recited in instant claims 94 and 104:
As discussed supra for claim 1, Kim teaches a peptide comprising the LG4 domain amino acid sequence (i.e., resides 1423-1447 of SEQ ID NO: 2) (See Kim specification, pg. 20, 1st paragraph; pg. 23, 1st paragraph).
Additionally, as discussed supra for claims 90, 99-100, and 109, Kim teaches wound coverings and scaffold for tissue engineering including a peptide having an amino acid sequence of SEQ ID NO: 1 in human laminin-5 alpha3 recombinant LG3 domain, fragments, or derivatives thereof (See Kim specification, pg. 14, last paragraph to pg. 15, 1st paragraph). Moreover, although Kim teaches that the LG3 domain amino acid sequence is utilized in a wound covering and scaffold and exhibited superior adhesion activity compared to the BSA control and to the LG4 domain amino acid sequence (See Kim specification, pg. 9, 3rd paragraph), the LG4 domain amino acid sequence exhibited superior adhesion activity compared to the BSA control (See Kim specification, pg. 23, 1st paragraph; Figures 2A-D). As such, the wound coverings and scaffold for tissue engineering can include a peptide comprising the amino acid sequence of any five LG domain of laminin 5 alpha3 chain.
The scaffolds include porous scaffolds prepared by synthetic biodegradable high molecular compounds such as poly amino acids, chitosan, and collagen (See Kim specification, pg. 15, last paragraph to pg. 16, 1st paragraph) thereby constituting a biomaterial scaffold. Kim also teaches that the scaffolds for tissue engineering include all scaffolds which can be used in the tissue engineering field for maintenance, improvements, or restoration of body functions by transplantation of a substitute for living body tissue (See Kim specification, pg. 15, last paragraph). Thus, Kim’s scaffold is not limited with respect to the type of scaffold and additional biomaterials that make up the scaffold.
Briquez et al. teaches growth factor delivery systems for skin wound healing where the delivery systems integrate ECM growth-factor binding domains (See Briquez, abstract). The ECM plays a fundamental role in coordinating growth factor signaling and in guiding injured skin tissue toward healing (See Briquez, pg. 483, col. 1, 2nd paragraph). As such, Briquez et al. teaches that understanding and mimicking the mechanisms by which the ECM controls growth factors is becoming critical for designing successful growth factor-based therapies (See Briquez, pg. 483, col. 1, 2nd paragraph). Since ECM naturally binds growth factors, useful growth factor-binding domains can be isolated from various ECM molecules (See Briquez, pg. 483, col. 2, 4th paragraph). Several growth factor-binding sites have been discovered within ECM proteins such as fibronectin, fibrinogen, tenascin C, and vitronectin (See Briquez, pg. 483, col. 2, 4th paragraph). Briquez et al. teaches a specific complex comprising vitronectin, insulin-like growth factor (IGF), IGF-binding protein (IGF-BP), and epidermal growth factor (EGF) that significantly accelerated reepithelization of non-healing ulcers when delivered to deep dermal partial thickness burns in a porcine model (See Briquez, pg. 484, col. 1, 2nd paragraph). Discovering and integrating ECM growth factor-binding domains into biomaterial matrices or using these domains topically is thus an interesting approach to efficiently deliver low doses of growth factors (See Briquez, pg. 484, col. 1, 2nd paragraph). Plus, growth factor-binding ECM fragments can be further engineered to enhance growth factor signaling (See Briquez, pg. 484, col. 1, 2nd paragraph). Moreover, Briquez et al. teaches that the formation of molecular complexes between growth factors and ECM proteins such as fibronectin and vitronectin, can considerably enhance growth factor signaling (See Briquez, pg. 484, col. 1, last paragraph to col. 2, 1st paragraph). In particular, ECM-protein-growth factor complexes can induce the formation of clusters between growth factor-receptors and integrins (See Briquez, pg. 484, col. 2, 1st paragraph).
Additionally, Briquez et al. teaches that growth factors can be covalently immobilized into a biomaterial matrix using chemical or enzymatic reactions (See Briquez, pg. 484, col. 2, 2nd paragraph). To overcome potential shortfalls of covalently binding of growth factors to a biomaterial matrix, Briquez et al. teaches covalently cross-linking growth factors into fibrin matrices through a specific transglutaminase peptide sequence (See Briquez, pg. 484, col. 2, last paragraph). As such, Briquez et al. teaches that growth factors including a growth factor binding domain, e.g., IGF-BP, can be covalently attached to an ECM matrix (note: same as a biomaterial scaffold) via a specific transglutaminase peptide sequence. It is noted that the scope of claims 93 and 103 encompasses where the peptide and collagen binding peptide are attached directly or indirectly thereby including where the two peptides are attached via a linking peptide.
Furthermore, Briquez et al. teaches a fusion protein comprising a growth factor, e.g., VEGF-A or PDGF-BB, with a PIGF-2 domain fragment at residues 123-144 where the attachment of the PIGF-2 domain fragment confers super-affinity for ECM proteins such as fibronectin, vitronectin, tenascin C, osteopontin, fibrinogen, and collagen I (See Briquez, pg. 486, col. 1, 1st paragraph to col. 2, 1st paragraph). Briquez et al. found that when this fusion protein is applied to skin wounds in diabetic mice, there was significantly faster wound closure and to more granulation tissue compared to wild-type growth factors (See Briquez, pg. 486, col. 2, 1st paragraph). As such, the PIGF-2 domain fragment constitutes a collagen binding peptide and is fused to a growth factor in order to facilitate wound healing and regenerate granulation tissue. Therefore, Briquez et al. suggests that attaching a growth factor or growth factor binding domain to a ECM matrix via a transglutaminase peptide sequence, or attaching a growth factor or growth factor binding domain to a collagen binding peptide such as PIGF-2123-144 domain improves wound healing and/or tissue regeneration in a subject.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the teachings of Kim and administer either (1) a transglutaminase peptide attached to the LG3 domain amino acid sequence of the laminin-5 alpha3 chain as a growth factor binding domain in order to efficiently cross-link the LG3 domain amino acid sequence into an ECM scaffold containing collagen-binding peptides such as fibronectin and victronectin thereby forming a biomaterial scaffold, or (2) a fusion protein comprising a PIGF-2123-144 domain fragment as a collagen binding peptide and the LG3 domain amino acid sequence of the laminin-5 alpha3 chain as a growth factor binding domain to a wound of a subject in order to regenerate tissue and/or facilitate wound healing. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because growth factors and growth factor binding domains were known to be attached either directly or indirectly via a transglutaminase peptide to collagen binding peptides either as a fusion protein or in an ECM matrix containing collagen binding peptides, and when fused together the growth factor binding domain and collagen binding peptide resulted in significantly faster wound closure and more granulation tissue in skin wounds in diabetic mice as taught by Briquez et al.
One of ordinary skill in the art before the effective filing date of the instant application would have had a reasonable expectation of success given that the biomaterial scaffold of Kim comprises a LG3 domain amino acid sequence from the laminin-5 alpha3 chain and a biodegradable polymer that is administered to skin wounds of a subject in order to regenerate tissue and/or facilitate wound healing, and therefore, modifying the administered biomaterial scaffold such that the scaffold is composed of ECM proteins including collagen binding peptides and attaching the LG3 domain amino acid sequence to the ECM scaffold via a transglutaminase peptide, or modifying the LG3 domain amino acid sequence of Kim to be fused to PIGF-2 domain fragment as a collagen binding peptide would support the regeneration of tissue and/or facilitation of wound healing of skin wounds in a subject by constituting the simple substitution of one known element for another to obtain predictable results and/or the use of known technique to improve similar devices (methods, or products) in the same way and/or the application of a known technique to a known device (method, or product) ready for improvement to yield predictable results and/or some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application, as evidenced by the references, especially in the absence of 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 90, 93, 97, 99-100, 103, 107, and 109 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,732,029 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because ‘029 claims:
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(See ‘029 claims 90-91, 93, 96, 102, and 104-105 thereby corresponding to issued claims 1-2, 4, 6, 12, and 15-16). It is noted that ‘029’s SEQ ID NO: 1 is 100% identical to the amino acid sequence depicted as SEQ ID NO: 1 in the instant specification at [0081] and Table 1. As such, assuming that the amino acid sequence of instant SEQ ID NO: 1 is the amino acid sequence depicted as SEQ ID NO: 1 in the instant specification at [0081] and Table 1, the ‘029 methods read of instant claims 90 and 100 as the ‘029 polypeptide only requires 25-100 amino acids in length. ‘029’s SEQ ID NO: 2 is 100% identical to instant SEQ ID NO: 2. ‘029 claim 4 is identical to instant claims 93 and 103. ‘029 claim 6 is identical to instant claims 97 and 107. ‘029 claim 12 reads on instant claims 99 and 109. Therefore, the ‘029 claimed invention anticipates the instantly claimed invention.
Examiner Comment
Notwithstanding the 112 rejections supra, the scope of claims 94 and 104 is free of the prior art. As discussed in the “Election/Restriction” section supra, the closest prior art is WO 2016/016269 A1. ‘269 teaches an anti-collagen antibody containing HCDR1-3 and LCDR1-3 represented as SEQ ID NOs: 3-8, respectively, or SEQ ID NOs: 11-12, 5, and 14-16, respectively (See ‘269, pg. 3, last paragraph to pg. 4, 1st paragraph). Moreover, ‘269 teaches a VL and VH chain amino acid sequences that are 100% identical to instant SEQ ID NOs: 63 and 65, respectively (See ‘269, SEQ ID NOs: 1-2). ‘269 also teaches that anti-collagen antibodies target epitopes within the type II collagen protein (major protein of the extracellular matrix of cartilage) and have the potential to target therapeutics to osteoarthritic joints (See ‘269, pg. 20, last paragraph). Plus, ‘269 teaches that the antibodies can be used to treat an inflammatory disorder, inhibiting angiogenesis, treating cancer and/or treating an autoimmune diseases such as lupus, rheumatoid arthritis, and osteoarthritis in a patient (See ‘269, pg. 13, 3rd paragraph; pg. 14, 3rd to 4th paragraph). However, ‘269 does not teach or suggest that the anti-collagen antibody or fragments thereof can be useful to treat skin wounds or facilitate wound healing by regenerating tissue. Furthermore, inhibiting angiogenesis would not be desirable in wound healing. Thus, the scope of claims 94 and 104 are free of the prior art.
Conclusion
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/THEA D' AMBROSIO/ Primary Examiner, Art Unit 1654