DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application, Amendments and/or Claims
The amendment and Applicant’s arguments, filed 10 July 2026, have been entered in full. Claims 8, 11, 15, 19-27 are canceled. Claims 1, 5, 6 and 12 are amended. Claims 1-7, 9-18 are under examination.
Information Disclosure Statement
The information disclosure statement(s) (IDS) (filed 10 July 2026) was received and complies with the provisions of 37 CFR §§1.97, 1.98 and MPEP § 609. It has been placed in the application file and the information referred to therein has been considered as to the merits.
Withdrawn Objections And/Or Rejections
The Duplicate Claim Warning, as set forth at pages 3-4 of the previous Office Action (24 March 2024), is withdrawn in view of the amendment (10 July 2026).
The rejection to claims 1-10, 14-18 under 35 U.S.C. 102(a1) and 35 U.S.C. 102(a1) as being anticipated by Lucas et al. (US 2018/093437; published July 12, 2018), as set forth at pages 5-7 of the previous Office Action (24 March 2024), is withdrawn in view of the amendment (10 July 2026).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-7, 9-18 remain rejected under 35 U.S.C. 103 as being unpatentable over Lucas et al. (US 2018/093437; published July 12, 2018) in view of Mousa et al. (US 2016/0206773; published July 21, 2016).
The basis for this rejection is set forth at pages 7-11 of the previous Office Action (24 March 2026).
APPLICANT’S ARGUMENTS: Applicant argues that the skilled artisan would not have arrived at the claimed invention upon reading of Lucas or Mousa, either alone or in combination, because preventing transplant rejection and promoting wound healing are fundamentally different objectives.
Applicant argues that Lucas is drawn to systemic or organ-level immunomodulation, and that the instant claims are drawn to tissue remodeling (e.g., collagen deposition and angiogenesis). Applicant argues that Lucas describes the use of an M-T7 polypeptide to prevent, block, or reduce transplant rejection by contacting donor tissue prior to implantation into a recipient. Applicant directs the Examiner’s attention to Lucas at paragraphs [0100] and [0101], [0157]. Applicant argues that Lucas is directed to immunomodulation-specifically, dampening the recipient's immune response-and does not describe altering the structural architecture of the donor tissue itself. Applicant maintains that Lucas preconditions the tissue to reduce immune-mediated rejection after implantation.
Applicant submits that the present invention is directed to promoting wound healing, including accelerating wound closure with a more properly organized architecture. Applicant argues that the distinction is significant because accelerated healing alone carries the risk of disorganized connective tissue deposition and subsequent scarring. Applicant argues that the present invention addresses this issue by not only accelerating closure but also enhancing structural organization. Applicant argues that M-T7 treatment induces an early TNFα response that drives a stronger VEGF response, promoting angiogenesis in the peri-wound area and contributing to both accelerated and structurally improved healing. Applicant directs the Examiner’s attention to paragraphs [00208] and [00216].
Applicant argues that Mousa does not cure these defects in Lucas.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
1. MPEP § 2112 provides guidance as to the Examiner’s burden of proof for a rejection of claims under 35 U.S.C. 102 or 103 based upon the express, implicit, and inherent disclosures of a prior art reference. The case law clearly states that something which is old does not become patentable upon the discovery of a new property. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property that 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).
Further, the court has held that 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); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) (“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.”); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed.Cir.1999). Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established and the burden of proof rests upon the Applicant to demonstrate that the prior art does not necessarily or inherently possess the characteristics of Applicant’s claimed product.
In the instant case, the claims are drawn to a topical product with the intended use of healing wounds.
As was stated in the previous Office Action, Lucas et al. teach a M-T7 polypeptide sequence that is 99% identical to instant SEQ ID NO:1 and a M-T7 polypeptide sequence that is 98.5% identical to instant SEQ ID NO:2.
The Examiner maintains that the polypeptide of Lucas et al. would have the functional properties as currently claimed.
2. Lucas et al. teach that compositions comprising the M-T7 polypeptides are useful in preventing, blocking and/or reducing rejection of a transplant and treating transplant vasculopathy (i.e. disease, damage, or dysfunction of blood vessels). Lucas et al. teach that the pharmaceutical compositions described herein can be delivered to the skin or to the external surfaces of organs. Lucas et al. teach that the pharmaceutical composition can be formulated for administration by any route of administration, including topical.
Lucas al. teach that pharmaceutical composition comprising the M-T7 derived polypeptides can be formulated as a gel.
Lucas et al. do not explicitly teach wherein the topical formulation is contained in a hydrophilic polymer.
Mousa et al. teach a composition and a method of applying a composition to a site on the body. Mousa et al. teach the composition includes a hydrogel matrix that includes at least one polymer cross-linked, via ionic or covalent bonding, with both hyaluronic acid and alginic acid. Mousa et al. teach that the at least one polymer is chitosan, poly L- Lysine, or a combination thereof. Mousa et al. teach that chitosan and poly L-Lysine are hydrophilic polymers. Mousa et al. teach using the composition for the treatment of wounds. Mousa et al. teach the composition can be used as a drug delivery vehicle for growth factors and other biologically active agents.
3. MPEP 2144 IV teaches: The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) ("One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings."); In re Linter, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972).
In the instant case, the combination of the Lucas and Mousa references do not have to teach the same purpose or to solve the same problem as the instant Inventors.
The scientific reasoning and evidence as a whole indicates that the rejection should be maintained.
NEW REJECTIONS/OBJECTONS
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 5 and 6 are rejected under 35 U.S.C. 102(a1) and 35 U.S.C. 102(a2) as being anticipated by Stern et al. (US 2013/0323202; published Dec. 5, 2013).
It is noted that the instant claims have been amended to recite a fragment thereof.
The instant specification teaches:
“..biologically active fragments can include polypeptides of about 5, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, or greater than 50 amino acids..” (see para 0070).
“Where the fragments include, at their N-terminus or C-terminus (or both), amino acid residues that are not naturally found in M-T7 the additional sequence(s), and can be about 200 amino acid residues long, and these residues can be divided evenly or unevenly between the N- and C-termini. For example, both the N- and C-termini can include about 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 amino acid residues” (see para 0080).
Stern et al. teach a method of treating ocular conditions such as keratoconjunctivitis and treating systemic diseases, such as Stevens-Johnson disease and graft versus host disease by administering IL-10 and TPV134R polypeptides (abstract and para 0002). Stern et al. teach that keratoconjunctivitis refers to dry eye disease, which a patient experiences as chronic dryness of the cornea and conjunctiva. Stern et al. teach patients with severe symptoms may develop microbial corneal ulceration (paras 0002 and 0051).
Stern et al. teach the myxoma virus M-T7 polypeptide sequence and the myxoma virus M-T7 polypeptide signal sequence (para 0005). Stern et al. teach in one embodiment; the TPV polypeptide can be modified to incorporate the M-T7 polypeptide signal sequence MDGRLVFLLASLAIVSDA. Stern et al. teach that one can use a fusion polypeptide comprising the myxoma T7 signal sequence in the methods of the invention. Stern et al. teach that point mutations, insertions, or deletions may be present in the M-T7 polypeptide signal sequence (paras 0025, 0027 and 0034)(applies to claims 5 and 6).
Stern et al. teach the therapeutic proteins of the present invention may contain hydrophilic polymers and polypeptides (para 0056). Stern et al. teach pharmaceutically acceptable carriers (paras 0056). Stern et al. teach recombinant methods of making the fusion protein (paras 0028-0031). Stern et al. teach that when administering the therapeutic proteins of the invention to treat conditions of the eye, the proteins may be administered topically to the eye (para 0054). Stern et al. teach that the therapeutic proteins of the invention may be administered locally to treat Stevens-Johnson disease, such as by topically applying a cream or gel containing the protein (para 0055).
Claim Rejections-35 USC § 112(a) or 35 U.S.C. 112 (pre-AIA ), First paragraph, Written description requirement
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 5 and 6 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.
It is noted that the instant claims have been amended to recite a fragment thereof.
The instant specification teaches: “..biologically active fragments can include polypeptides of about 5, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, or greater than 50 amino acids..” (see para 0070). “Where the fragments include, at their N-terminus or C-terminus (or both), amino acid residues that are not naturally found in M-T7 the additional sequence(s), and can be about 200 amino acid residues long, and these residues can be divided evenly or unevenly between the N- and C-termini. For example, both the N- and C-termini can include about 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 amino acid residues”(see para 0080).
Based on the definition of “fragments thereof” taught in the instant specification, the instant claims are drawn to a genus of undisclosed M-T7 polypeptides having the function of healing wounds with no structural limitations. The number of structures encompassed by the genus may be vast or conversely there may be no structures that possess the claimed function. The disclosure fails to describe the common attributes or characteristics that identify the members of the genus.
The claims read on a sequence having any number of substitutions, deletions and/or insertions at every position with respect to the wild-type sequence as long as it retains function of healing wounds.
MPEP§ 2163 states that the written description requirement for a claimed genus may be satisfied through establishment of a structure-function correlation (show a structure is correlated with the function) OR through a sufficient description of a representative number of species (show a representative number of species that have the function. There must be enough species that are representative of the full breadth of the genus).
Regarding structure-function correlation: The problem of predicting protein structure and in turn utilizing predicted structural determinations to ascertain functional aspects of the protein is extremely complex. It is in no way predictable that randomly selected changes in the disclosed sequence would afford a protein having activity comparable to the one disclosed.
For sequences having one or two substitutions, for example, the artisan would reasonably expect that many of the possible variants would retain functional properties comparable to those of the unmodified protein, and it would require only routine manipulations to make and test a reasonably representative sampling of the possible variants. However, as the number of modified sites increases, the number of possible variants, and hence the degree of experimentation required, increases exponentially. Additionally, as plural substitutions are introduced, their interactions with each other and their effects on the structure and function of the protein become progressively less predictable.
Even if the instant specification outlined art-recognized procedures for producing and screening for active muteins, this is not adequate guidance as to the nature of active derivatives that may be constructed, but is merely an invitation to the artisan to use the current invention as a starting point for further experimentation. The ordinary artisan would immediately recognize that an active or binding site must assume the proper three-dimensional configuration to be active; conformation is dependent upon surrounding residues. Substitution of non-essential residues can often destroy activity
For example, Fenton et al. state that while it is well known that most substitutions at conserved amino acid positions (which they call “toggle” switches) abolish function, it is also true that substitutions at non-conserved positions (which they call “rheostat” positions) are equally capable of affecting protein function. They conclude that substitutions at rheostat positions have highly unpredictable outcomes on the activities and specificities of protein-based drugs (see entire reference)(Rheostat positions: A new classification of protein positions relevant to pharmacogenomics Medicinal Chemistry Research 29:1133-1146; 2020).
Bhattacharya et al. state that the range of possible effects of even single nucleotide variations at the protein level are significantly greater than currently assumed by existing software prediction methods, and that correct prediction of consequences remains a significant challenge (p. 18)(Impact of genetic variation on three dimensional structure and function of proteins PLoS ONE 12(3): e0171355; 2017). See also Tokuriki et al. (Stability effects of mutations and protein evolvability, Current Opinion in Structural Biology, 19:596-604, 2009).
In addition, when multiple mutations are introduced, there is even less predictability. As the number of modified sites increases, the number of possible variants, and hence the degree of experimentation required, increases exponentially. As plural substitutions are introduced, their interactions with each other and their effects on the structure and function of the protein become progressively less predictable. For evidence thereof, see Guo et al., who state that the effects of mutations on protein function are largely additive (page 9207, left column, full paragraph 2)(Guo et al. Protein tolerance to random amino acid change. PNAS USA 101(25):9205-10; 2004).
The state of the prior art evidences the unpredictability of the effects of mutation on protein structure and function.
Regarding a representative number of species: The instant specification fails to describe a representative number of species to provide adequate written description of the claimed genus as per MPEP § 2163. There must be enough species that are representative of the full breadth of the genus. A "representative number of species" means that the species, which is adequately described, is representative of the entire genus. When there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, the specification teaches SEQ ID NO: 1 and SEQ ID NO: 2, wherein SEQ ID NO:1 comprises SEQ ID NO:2 and an N-terminal signal sequence peptide.
A disclosure of 2 species is not representative of the claimed genus, which encompasses non-structurally defined M-T7 polypeptides having the required function encompassed by the claims. There is substantial variation within the genus and the instant specification fails to describe a sufficient variety of species to reflect the variation within the genus. There must be enough species that are representative of the full breadth of the genus.
There is no information regarding what structural features would likely be associated with such function. The specification does not describe the structure for substitution variants, deletion variants or insertion variants with the biological function. Those of ordinary skill in the art could predict which part of the structure can vary without losing activity, particularly in view of the therapeutic intentions. The level of skill and knowledge in the art is such that one of ordinary skill would not be able to identify without further testing which of those molecules have the claimed activity.
The claims depend on a recited property, where the claim covers every conceivable structure for achieving the stated property, while the instant specification fails to describe any species with sufficient identifying characteristics such that one skill in the art could visualize or recognize the identity of the claimed subject matter. The specification fail to teach the structural identifying characteristics that are applicable to the genus. The skilled artisan cannot envision the detailed chemical structure of the encompassed claimed molecules (if any) which have the activity without further testing, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of identification.
The artisan would have no resort, save trial-and-error experimentation, to screen an astronomically large number of possible structural variants of M-T7 to discern the associated function of wound healing.
The courts have specifically stated that the skilled artisan cannot envision the detailed chemical structure of an encompassed polypeptide until the structure is disclosed, 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, the full breadth of the claims does not meet the written description provision of 35 U.S.C. §112, first paragraph.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REGINA M DEBERRY whose telephone number is (571)272-0882. The examiner can normally be reached M-F 9:00-6:30 pm (alt Fri).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/R.M.D/Examiner, Art Unit 1647 9/15/2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
Prosecution Insights