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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on August 6, 2025 has been entered.
Status of the Claims
Claims 1-7 were originally filed February 8, 2021.
Claims 1-8 were filed February 8, 2021.
The amendment received July 27, 2023 amended claim 4 and canceled claim 8.
The amendment received December 20, 2023 amended claims 1-7, canceled claim 8, and added new claim 9.
The amendment received May 28, 2024 and entered with the RCE filed June 24, 2024 amended claims 1, 2, 7, and 9.
The amendment received February 24, 2025 amended claims 1, 2, and 7 and added new claims 10 and 11.
The amendment received August 6, 2025 amended claims 7 and 11 and canceled claim 10. Please note: claims 2 and 7 have improper status identifiers of “Withdrawn”.
Claims 1-7, 9, and 11 are currently pending.
Claims 1, 2, 7, 9, and 11 are currently under consideration.
Election/Restrictions
Applicants elected, with traverse, Group I in the reply filed on July 27, 2023. The traversal is on the grounds that SEQ ID NO: 1 is the inventive concept linking all of Groups I-IV. This is not found persuasive because applicants did not address the prior art of record utilized to break unity of invention. The requirement is still deemed proper and is therefore made FINAL. Claims 3-6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on July 27, 2023.
Applicants elected, with traverse, SEQ ID NO: 1 in the reply filed on July 27, 2023. The traversal is on the grounds that SEQ ID NO: 1 is the inventive concept linking all of the species. This is not found persuasive because applicants did not address the prior art of record utilized to break unity of invention. The requirement is still deemed proper and is therefore made FINAL.
Please note: claim 7 should be withdrawn due to the election of SEQ ID NO: 1 alone. However, due to various issues with claim 7, the claim has been examined.
Please note: claim 2 should be withdrawn due to the election of SEQ ID NO: 1 alone. However, due to various issues with the claim, the claim has been examined.
Please note: claims 9 and 10 should be withdrawn due to the election of SEQ ID NO: 1 alone. However, due to various issues with the claims, the claims have been examined.
Please note: applicants’ representative continues to amend claims with nonelected species or adding new claims which are drawn to nonelected species. This is the LAST time any amended or new claims that do not read on the elected species will be considered. In addition, amended or new claims may require a new restriction and/or species requirement.
Priority
The present application is a 371 (National Stage) of PCT/IN2019/050578 filed August 8, 2019 and claims foreign priority to India 201841029835 filed August 8, 2018.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Sequence Interpretation
The Office interprets claims comprising SEQ ID NOs: in the following manner: “comprising a sequence of SEQ ID NO: 1” requires only a 2mer of SEQ ID NO: 1, “comprising the sequence of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 with any N-/C-terminal additions or any 5’/3’ additions, “consisting of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 and the same length as SEQ ID NO: 1, and “selected from the group consisting of SEQ ID NOs: 1, 2, and 3” requires the full-length sequence with 100% identity to SEQ ID NOs: 1, 2, or 3 and the same length as SEQ ID NOs: 1, 2, or 3. Any length restriction requires that specific length.
Withdrawn Objection
The objection to claim 11 regarding “concentration is of” should read “concentration of” is withdrawn in view of the amendment received August 6, 2025.
Withdrawn Rejection
The rejection of claim 10 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 (new matter) is withdrawn in view of the cancellation of the claim in the amendment received August 6, 2025.
New Rejection Necessitated by Amendment
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 7 and 9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection. Support in the originally filed specification was not found for SEQ ID NO: 1/TGF a being retained by an alginate scaffold matrix. Applicants point to page 5 of the originally filed specification for support. An alginate scaffold is referred to once in the originally filed specification. Page 5, lines 9-12 reads “Yet another object of this invention is to provide a Recombinant Transforming Growth Factor Alpha (TGFa), which when delivered using an alginate scaffold matrix in the wound site, can heal the chronic wounds in a shorter period by remodeling the epithelial tissues with minimal scar formation.”. Thus, SEQ ID NO: 1 is not referred to and it is unclear if or how the alginate scaffold matrix “retains” TGFa. It is presumed that TGFa is on the surface or is released by the alginate scaffold in order to heal the chronic wounds. However, it is unclear if the delivery is via TGFa being on the surface, encapsulated with the alginate scaffold, covalently attached, etc.
Maintained and/or Modified* Rejections
*wherein the modification is due to amendment
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 11 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection. No where in the originally filed specification is it specified that SEQ ID NO: 1 is provided at concentrations of 0.025 mg/ml, 0.25 mg/ml, or 2.5 mg/ml. Figure 3 and page 7 refer to 0.025 mg, 0.25 mg, or 2.5 mg, but a specific concentration or dilution volume is not referred to and the amount is for TGF a (i.e. not clear if this is SEQ ID NO: 1 or not). Page 18 and Example 7 refer to 0.025 mg/ml, 0.25 mg/ml, or 2.5 mg/ml. However, it is not clear if this is for SEQ ID NO: 1 or not since only TNF a is referred to. As a reminder, applicants must specifically point out support in the originally filed specification for any amendments (e.g. page and line numbers). Applicants may not simply provide generic statements such as “support for which is found throughout the specification and in the claims as originally filed”.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 112(a)(new matter), for claim 11 were considered but are not persuasive for the following reasons.
Applicants contend that the claim has support at page 18 and Example 7 and that utilization of TGF a overcomes the rejection.
Applicants’ arguments are not convincing because while page 18 and Example 7 refer to 0.025 mg/ml, 0.25 mg/ml, or 2.5 mg/ml of TGF a, it is not clear if this is for SEQ ID NO: 1 or not since only TNF a is referred to.
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 7 and 9 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. One of skill in the art would not be able to determine the scope of the presently claimed product. For example, it is unclear how the alginate and/or alginate scaffold matrix is “retained by” the peptide of SEQ ID NO: 1.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 112(b) (indefinite), for claims 7 and 9 were considered but are not persuasive for the following reasons.
Applicants contend that the amendment to claim 7 (i.e. retained by) negates the rejection.
Applicants’ arguments are not convincing since the claim requires clarification since the alginate scaffold matrix may alter the 35 USC 101 rejection for the claims based on the association of SEQ ID NO: 1 and the alginate scaffold matrix (e.g. just as the fused to GST language overcomes a 35 USC 101 rejection). Furthermore, an alginate scaffold is referred to once in the originally filed specification. Page 5, lines 9-12 reads “Yet another object of this invention is to provide a Recombinant Transforming Growth Factor Alpha (TGFa), which when delivered using an alginate scaffold matrix in the wound site, can heal the chronic wounds in a shorter period by remodeling the epithelial tissues with minimal scar formation.”. Thus, SEQ ID NO: 1 is not referred to and it is unclear if or how the alginate scaffold matrix “retains” TGFa. It is presumed that TGFa is on the surface or is released by the alginate scaffold in order to heal the chronic wounds. However, it is unclear if the delivery is via TGFa being on the surface, encapsulated with the alginate scaffold, covalently attached, etc.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 7, 9, and 11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to SEQ ID NO: 1 (fragment of TGF-a) without significantly more. Regarding the pharmaceutical composition of claims 7 and 9, since the claim is silent with regard to how the peptide fragment of SEQ ID NO: 1 is associated with the alginate scaffold matrix, the claim encompasses a composition wherein both are not associated with each other directly. This judicial exception is not integrated into a practical application because the present claims are drawn to products. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because either additional elements are not present (i.e. claim 1) or the additional elements are not directly associated with the peptide fragment of SEQ ID NO: 1 and/or alginate scaffold matrix is well-understood, routine, and conventional in the prior art.
RESULT 1
F8WA74_HUMAN
ID F8WA74_HUMAN Unreviewed; 120 AA.
AC F8WA74;
DT 21-SEP-2011, integrated into UniProtKB/TrEMBL.
DT 21-SEP-2011, sequence version 1.
DT 22-FEB-2023, entry version 64.
DE SubName: Full=Transforming growth factor alpha {ECO:0000313|Ensembl:ENSP00000377787.3};
DE Flags: Fragment;
GN Name=TGFA {ECO:0000313|Ensembl:ENSP00000377787.3};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000313|Ensembl:ENSP00000377787.3, ECO:0000313|Proteomes:UP000005640};
RN [1] {ECO:0000313|Ensembl:ENSP00000377787.3, ECO:0000313|Proteomes:UP000005640}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [2] {ECO:0000313|Ensembl:ENSP00000377787.3}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (OCT-2022) to UniProtKB.
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|PROSITE-ProRule:PRU00076}.
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DR EMBL; AC005234; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC017084; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; F8WA74; -.
DR SMR; F8WA74; -.
DR PeptideAtlas; F8WA74; -.
DR Antibodypedia; 16331; 1408 antibodies from 39 providers.
DR Ensembl; ENST00000394241.3; ENSP00000377787.3; ENSG00000163235.16.
DR UCSC; uc061kjk.1; human.
DR HGNC; HGNC:11765; TGFA.
DR VEuPathDB; HostDB:ENSG00000163235; -.
DR GeneTree; ENSGT00940000160058; -.
DR ChiTaRS; TGFA; human.
DR Proteomes; UP000005640; Chromosome 2.
DR Bgee; ENSG00000163235; Expressed in esophagus squamous epithelium and 174 other tissues.
DR ExpressionAtlas; F8WA74; baseline and differential.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; IEA:UniProt.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR Gene3D; 2.10.25.10; Laminin; 1.
DR InterPro; IPR000742; EGF-like_dom.
DR PANTHER; PTHR10740:SF1; PROTRANSFORMING GROWTH FACTOR ALPHA; 1.
DR PANTHER; PTHR10740; TRANSFORMING GROWTH FACTOR ALPHA; 1.
DR PRINTS; PR00009; EGFTGF.
DR SUPFAM; SSF57196; EGF/Laminin; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
PE 1: Evidence at protein level;
KW Disulfide bond {ECO:0000256|PROSITE-ProRule:PRU00076};
KW EGF-like domain {ECO:0000256|PROSITE-ProRule:PRU00076};
KW Membrane {ECO:0000256|SAM:Phobius};
KW Proteomics identification {ECO:0007829|PeptideAtlas:F8WA74};
KW Reference proteome {ECO:0000313|Proteomes:UP000005640};
KW Signal {ECO:0000256|SAM:SignalP}; Transmembrane {ECO:0000256|SAM:Phobius};
KW Transmembrane helix {ECO:0000256|SAM:Phobius}.
FT SIGNAL 1..22
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 23..120
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5003379426"
FT TRANSMEM 98..119
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT DOMAIN 42..82
FT /note="EGF-like"
FT /evidence="ECO:0000259|PROSITE:PS50026"
FT DISULFID 72..81
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00076"
FT NON_TER 120
FT /evidence="ECO:0000313|Ensembl:ENSP00000377787.3"
SQ SEQUENCE 120 AA; 12460 MW; 1CE9DCA5706B902E CRC64;
Query Match 100.0%; Score 296; DB 40; Length 120;
Best Local Similarity 100.0%;
Matches 51; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy VVSHFNDCPDSHTQFCFHGTCRFLVQEDKPACVCHSGYVGARCEHADLLAV 51
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db
VVSHFNDCPDSHTQFCFHGTCRFLVQEDKPACVCHSGYVGARCEHADLLAV
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 101 as being drawn to a judicial exception for claims 1, 7, 9, and 11 were considered but are not persuasive for the following reasons.
Applicants contend that the fragment does not occur naturally as a single expressed protein and that the lack of an N-terminal methionine negates the rejection.
Applicants’ arguments are not convincing since it does not matter if the hand of man is present (i.e. making a fragment which is not found in nature; see Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 589-91, 106 USPQ2d 1972, 1978-79 (2013) and University of Utah Research Foundation v. Ambry Genetics Corp., 774 F.3d 755, 761, 113 USPQ2d 1241, 1244 (Fed. Cir. 2014)). Furthermore, it is respectively noted that mature TGF a is a 50mer which presumably folds similarly to present SEQ ID NO:1 since this “fragment” (51mer) is taken from the loop region which is cleaved from the transmembrane region and released as soluble TGF a. In addition, the MW would be similar. Furthermore, neoplastic cells can release TGF a of various lengths. See Luetteke et al., 1990, Transforming growth factor alpha: expression, regulation and biological action of its integral membrane precursor, Semin Cancer Biol, 1(4): 265-275 (abstract only). Thus, applicants have not met the burden of showing that the 51mer is not naturally occurring via some structural change. Please also refer to Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 589-91, 106 USPQ2d 1972, 1978-79 (2013) regarding isolated DNA and University of Utah Research Foundation v. Ambry Genetics Corp., 774 F.3d 755, 761, 113 USPQ2d 1241, 1244 (Fed. Cir. 2014) regarding single-stranded DNA fragments known as "primers". Moreover, the fragment does not have any distinguishing “markedly different characteristics” from TGF a as evidenced by the ability of TGF a to be involved in wound healing (please refer to the present specification; references will be provided upon request).
The examiner of record has provided a sequence alignment to show that SEQ ID NO: 1 is a fragment of a naturally occurring protein (i.e. TGFa) thus meeting the burden of proof. Applicants’ own specification states that SEQ ID NO: 1 is a fragment of TGFa (see pages 6 and 14).
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 1, 2, and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Harari U.S. Patent Application Publication 2009/0131308 published May 21, 2009.
For present claims 1, 2, and 11, Harari teaches a 52mer of SEQ ID NO: 8 (i.e. 100% identity to present SEQ ID NO: 1 which is a 51mer) and truncations, deletions, variants, or fragments including a single amino acid truncation/deletion for wound healing (please refer to the entire specification particularly paragraphs 3, 8, 10, 13, 14, 19, 23, 25-27, 37, 65-68, 77, 81, 92, 99, 100, 108, 142, 177, 209, 225; Tables 1, 2, and 6; claims). In addition, Harari teaches fusion polypeptides comprising glutathione S-transferase (GST) and ErbB ligands (i.e. TGF a; please refer to the entire specification particularly paragraph 169). Harari teaches concentrations of 0.3 mM, 0.6 mM, 1.25 mM, 2.5 mM, 5 mM, and a range of up to 10 mM and dilutions of 200 mM (2.5 mg/ml = 0.5 mM TGF a; 0.25 mg/ml = 0.05 mM TGF a; 0.025 mg/ml = 0.005 mM TGF a; please refer to the entire specification particularly Figure 3; paragraphs 248, 250-253).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); and In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990) (Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
Therefore, the presently claimed TGF-a is anticipated by the teachings of Harari.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 102 (a)(1) as being anticipated by Harari for claims 1, 2, and 11 were considered but are not persuasive for the following reasons.
Applicants contend that Harari does not teach a 51mer.
Applicants’ arguments are not convincing since the teachings of Harari anticipate the TGF a fragment of SEQ ID NO: 1. Harari teaches a 52mer of SEQ ID NO: 8 which has 100% identity to the presently claimed 51mer of SEQ ID NO: 1 (please refer to the entire specification particularly SEQ ID NO: 8) and truncations, deletions, variants, or fragments including a single amino acid truncation/deletion for wound healing (please refer to the entire specification particularly paragraphs 3, 8, 10, 13, 14, 19, 23, 25-27, 37, 65-68, 77, 81, 92, 99, 100, 108, 142, 177, 209, 225; Tables 1, 2, and 6; claims). Harari teaches that TGF alpha is a ligand for ErbB receptors and part of the ErbB family (please refer to the entire specification particularly paragraph 3; Tables 1, 2, and 6). Harari teaches ErbB ligand fragments (please refer to the entire specification particularly paragraphs 13, 14, 19, 23, 25, 67, 68, 77, 81, 92, 99, 142, 177, 225).
"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." See In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) and In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989).
A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." See Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015) (quoting In re Petering, 301 F.2d 676, 681(CCPA 1962)). One of skill in the art would have a Ph.D., an M.D., etc. One of skill in the art would recognize that a single amino acid deletion on the terminus would not alter the function of the peptide. In addition, one of skill in the art could readily test a single amino acid deletion for function. However, it is respectfully noted that the present is a product only (i.e. not a method of utilizing the product), thus, the product simply has to exist (i.e. a specific function is not required).
Claims 1 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Adams et al. U.S. Patent 2004/0248196 published December 9, 2004.
For present claims 1 and 11, Adams et al. teach a 52mer of SEQ ID NO: 6 (i.e. 100% identity to present SEQ ID NO: 1 which is a 51mer) and a single amino acid deletion (please refer to the entire specification particularly paragraphs 2, 7, 75, 118, 175; Figure 2; claims).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); and In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990) (Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
Therefore, the presently claimed TGF-a is anticipated by the teachings of Adams et al.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 102 (a)(1) as being anticipated by Adams et al. for claims 1 and 11 were considered but are not persuasive for the following reasons.
Applicants contend that the teaching of Adams et al. only refers to a 52mer and does not specifically teach deletions to SEQ ID NO: 6.
Applicants’ arguments are not convincing since the teachings of Adams et al. anticipate a TGF a peptide consisting of SEQ ID NO: 1. Adams et al. teach SEQ ID NO: 6 which has 100% identity to present SEQ ID NO: 1 but is a 52mer instead of a 51mer (please refer to the entire specification particularly SEQ ID NO: 6). Adams et al. also teach TGF a variants including deletions (please refer to the entire specification particularly paragraphs 75, 118).
"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." See In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) and In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989).
A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." See Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015) (quoting In re Petering, 301 F.2d 676, 681(CCPA 1962)). One of skill in the art would have a Ph.D., an M.D., etc. One of skill in the art would recognize that a single amino acid deletion on the terminus would not alter the function of the peptide. In addition, one of skill in the art could readily test a single amino acid deletion for function. However, it is respectfully noted that the present is a product only (i.e. not a method of utilizing the product), thus, the product simply has to exist (i.e. a specific function is not required).
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.
Claims 1, 2, 7, 9, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Harari U.S. Patent Application Publication 2009/0131308 published May 21, 2009; McCarthy et al. U.S. Patent Application Publication 2004/0243043 published December 2, 2004; Vikis et al., 2004, Glutathione-S-Transferase-Fusion Based Assays for Studying Protein-Protein Interactions, Methods in Molecular Biology: Protein-Protein Interactions: Methods and Applications (Ed. Haian Fu), 261: 175-185; and Schultz et al., 1986, Epithelial Wound Healing Enhanced by Transforming Growth Factor-a and Vaccinia Growth Factor, Science, 235: 350-252.
For present claims 1, 2, 7, 9, and 11, Harari teaches a 52mer of SEQ ID NO: 8 (i.e. 100% identity to present SEQ ID NO: 1 which is a 51mer) and truncations, deletions, variants, or fragments including a single amino acid truncation/deletion for wound healing (please refer to the entire specification particularly paragraphs 3, 8, 10, 13, 14, 19, 23, 25-27, 37, 65-68, 77, 81, 92, 99, 100, 108, 142, 177, 209, 225; Tables 1, 2, and 6; claims). In addition, Harari teaches pharmaceutically acceptable diluents or carriers to create a variety of different pharmaceutical compositions (please refer to the entire specification particularly paragraphs 30, 205, 209). Furthermore, Harari teaches fusion polypeptides comprising glutathione S-transferase (GST) and ErbB ligands (i.e. TGF a; please refer to the entire specification particularly paragraph 169). Harari teaches concentrations of 0.3 mM, 0.6 mM, 1.25 mM, 2.5 mM, 5 mM, and a range of up to 10 mM and dilutions of 200 mM (2.5 mg/ml = 0.5 mM TGF a; 0.25 mg/ml = 0.05 mM TGF a; 0.025 mg/ml = 0.005 mM TGF a; please refer to the entire specification particularly Figure 3; paragraphs 248, 250-253).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); and In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990) (Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
Also see Schultz et al. which teaches providing 10, 1, or 0.1 mg/ml TGF-a for wound healing (please refer to the entire reference particularly Figures 1 and 2; Table 1; pages 350, 351).
However, Harari does not teach an alginate scaffold matrix.
For present claims 7 and 9, McCarthy et al. teach TGF-a and alginate wound dressings including a wettable polymer matrix, a sponge, mats, mesh, etc. (please refer to the entire specification particularly the abstract; paragraphs 17, 20, 22-24, 26, 44-46, 64, 150, 234; claims).
However, Harari does not specifically teach the addition of TGF-a at the C-terminus of GST. It is respectfully noted that the addition of TGF-a at the C-terminus or N-terminus of GST would be obvious variants to one of ordinary skill in the art. For clarity of the record, the following is provided.
For present claim 2, Vikis et al. teach fusion of polypeptides to the C-terminus of GST (please refer to the entire reference particularly the abstract; Introduction; Figures 1, 2).
The claims would have been obvious because a particular known technique (i.e. adding an alginate scaffold matrix to TGF-a; adding a polypeptide to the C-terminus of GST) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Harari; McCarthy et al.; Vikis et al.; and Schultz et al. for claims 1, 2, 7, 9, and 11 were considered but are not persuasive for the following reasons.
Applicants contend that neither Harari; McCarthy et al.; Vikis et al., and Schultz et al. teach the 51mer of SEQ ID NO: 1.
Applicants’ arguments are not convincing since the teachings of Harari, McCarthy et al., Vikis et al., and Schultz et al. render the TGF a or pharmaceutical composition of the instant claims prima facie obvious.
Harari teaches a 52mer of SEQ ID NO: 8 which has 100% identity to the presently claimed 51mer of SEQ ID NO: 1 (please refer to the entire specification particularly SEQ ID NO: 8) and truncations, deletions, variants, or fragments including a single amino acid truncation/deletion for wound healing (please refer to the entire specification particularly paragraphs 3, 8, 10, 13, 14, 19, 23, 25-27, 37, 65-68, 77, 81, 92, 99, 100, 108, 142, 177, 209, 225; Tables 1, 2, and 6; claims). Harari teaches that TGF alpha is a ligand for ErbB receptors and part of the ErbB family (please refer to the entire specification particularly paragraph 3; Tables 1, 2, and 6). Harari teaches ErbB ligand fragments (please refer to the entire specification particularly paragraphs 13, 14, 19, 23, 25, 67, 68, 77, 81, 92, 99, 142, 177, 225).
"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." See In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) and In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989).
A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." See Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015) (quoting In re Petering, 301 F.2d 676, 681(CCPA 1962)). One of skill in the art would have a Ph.D., an M.D., etc. One of skill in the art would recognize that a single amino acid deletion on the terminus would not alter the function of the peptide. In addition, one of skill in the art could readily test a single amino acid deletion for function. However, it is respectfully noted that the present is a product only (i.e. not a method of utilizing the product), thus, the product simply has to exist (i.e. a specific function is not required).
Claims 1, 2, 7, 9, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Adams et al. U.S. Patent 2004/0248196 published December 9, 2004; Harari U.S. Patent Application Publication 2009/0131308 published May 21, 2009; McCarthy et al. U.S. Patent Application Publication 2004/0243043 published December 2, 2004; Vikis et al., 2004, Glutathione-S-Transferase-Fusion Based Assays for Studying Protein-Protein Interactions, Methods in Molecular Biology: Protein-Protein Interactions: Methods and Applications (Ed. Haian Fu), 261: 175-185; and Schultz et al., 1986, Epithelial Wound Healing Enhanced by Transforming Growth Factor-a and Vaccinia Growth Factor, Science, 235: 350-252.
For present claims 1, 2, 7, 9, and 11, Adams et al. teach a 52mer of SEQ ID NO: 6 (i.e. 100% identity to present SEQ ID NO: 1 which is a 51mer) and a single amino acid deletion (please refer to the entire specification particularly paragraphs 2, 7, 75, 118, 175; Figure 2; claims). In addition, Adams et al. teach pharmaceutically acceptable carriers and diluents (please refer to the entire specification particularly paragraph 123).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); and In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990) (Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
Also see Schultz et al. which teaches providing 10, 1, or 0.1 mg/ml TGF-a for wound healing (please refer to the entire reference particularly Figures 1 and 2; Table 1; pages 350, 351).
However, Adams et al. do not teach a GST fusion polypeptide.
For present claims 1, 2, 7, 9, and 11, Harari teaches a 52mer of SEQ ID NO: 8 (i.e. 100% identity to present SEQ ID NO: 1 which is a 51mer) and truncations, deletions, variants, or fragments including a single amino acid truncation/deletion for wound healing (please refer to the entire specification particularly paragraphs 3, 8, 10, 13, 14, 19, 23, 25-27, 37, 65-68, 77, 81, 92, 99, 100, 108, 142, 177, 209, 225; Tables 1, 2, and 6; claims). In addition, Harari teaches pharmaceutically acceptable diluents or carriers to create a variety of different pharmaceutical compositions (please refer to the entire specification particularly paragraphs 30, 205, 209). Furthermore, Harari teaches fusion polypeptides comprising glutathione S-transferase (GST) and ErbB ligands (i.e. TGF a; please refer to the entire specification particularly paragraph 169). Harari teaches concentrations of 0.3 mM, 0.6 mM, 1.25 mM, 2.5 mM, 5 mM, and a range of up to 10 mM and dilutions of 200 mM (2.5 mg/ml = 0.5 mM TGF a; 0.25 mg/ml = 0.05 mM TGF a; 0.025 mg/ml = 0.005 mM TGF a; please refer to the entire specification particularly Figure 3; paragraphs 248, 250-253).
However, Harari does not specifically teach the addition of TGF-a at the C-terminus of GST. It is respectfully noted that the addition of TGF-a at the C-terminus or N-terminus of GST would be obvious variants to one of ordinary skill in the art. For clarity of the record, the following is provided.
For present claim 2, Vikis et al. teach fusion of polypeptides to the C-terminus of GST (please refer to the entire reference particularly the abstract; Introduction; Figures 1, 2).
However, Adams et al. do not an alginate scaffold matrix.
For present claims 7 and 9, McCarthy et al. teach TGF-a and alginate wound dressings including a wettable polymer matrix, a sponge, mats, mesh, etc. (please refer to the entire specification particularly the abstract; paragraphs 17, 20, 22-24, 26, 44-46, 64, 150, 234; claims).
The claims would have been obvious because a particular known technique (i.e. making GST-TGF a fusion polypeptides wherein TGF a is at the C-terminus of GST; adding alginate to TGF-a) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Adams et al.; Harari; McCarthy et al.; Vikis et al.; and Schultz et al. for claims 1, 2, 7, and 9, and 11 were considered but are not persuasive for the following reasons.
Applicants contend that Adams et al.; Harari; McCarthy et al.; Vikis et al.; and Schultz et al. do not teach the 51mer of present SEQ ID NO: 1.
Applicants’ arguments are not convincing since the teachings of Adams et