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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6/18/26 has been entered.
Priority
The instant application, filed 03/02/2023 and having 1 RCE-type filing therein is a National Stage entry of PCT/US21/49284 , International Filing Date: 09/07/2021
PCT/US21/49284 Claims Priority from Provisional Application 63112840 , filed 11/12/2020
PCT/US21/49284 Claims Priority from Provisional Application 63076516 , filed 09/10/2020.
Claim Status
Claims 1-3, 5-21 are pending and under examination.
Claims 4 and 22 are cancelled.
Claims 1-3, 5-21 are rejected.
Information Disclosure Statement
The Examiner has considered the reference(s) provided in the 7/15/26 Information Disclosure Statement, and provides a signed and dated copy of such herewith.
Drawings Objection
Response to Arguments
Applicant's arguments filed 6/18/26 have been fully considered but they are not persuasive.
Applicant has filed a Petition regarding color drawings, and new drawings, however the Petition has not yet been granted.
The drawings filed 6/18/26 are objected to until the Petition regarding color drawings is granted.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
Response to Arguments
Applicant's arguments filed 6/18/26 have been fully considered but they are not persuasive.
Although Applicant has filed a Petition regarding color drawings, and new drawings, the Petition has not yet been granted.
The examiner does not find any relevant argument or remark specifically pertaining to the specification objection, below, and accordingly this objection is maintained. An appropriate response, simpler than petitioning for color drawings, could be amending the Brief Description of the Drawings to not refer to colors in the Drawings.
The disclosure is objected to because of the following informalities: The Brief Description of the Drawings refers to colors in the drawings, however the Petition for color drawings has not been approved so this objection remains
Claim Interpretation – Retained for the Record
The claims limitations are given their broadest reasonable interpretation (BRI), (“[T]he ordinary and customary meaning of a claim term is the meaning that the term would have to a person of ordinary skill in the art in question at the time of the invention, i.e., as of the effective filing date of the patent application.” Phillips v. AWH Corp., 75 USPQ2d 1321, 1326 (Fed. Cir. 2005) (en banc).) The broadest reasonable interpretation of the claims must also be consistent with the interpretation that those skilled in the art would reach.” MPEP 2111, with reference to In re Cortright, 49 USPQ2d 1464, 1468. The claim limitations are given their BRI consistent with the specification, MPEP 2111, and under the BRI, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification, MPEP 2111.01.
This Claim Interpretation section is revised based on the 2/13/26 claim amendments to claims 1, 5 and 21 amending “having” to “consisting essentially of.”
The examiner finds support for “consisting essentially of” in paras 37 and 51 of the corresponding PGPUB US 20230331817.
Per the MPEP 2111.03 III, “The transitional phrase "consisting essentially of" limits the scope of a claim to the specified materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention,” this followed in the same paragraph with, “For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising." See, e.g., PPG, 156 F.3d at 1355, 48 USPQ2d at 1355 ("PPG could have defined the scope of the phrase ‘consisting essentially of’ for purposes of its patent by making clear in its specification what it regarded as constituting a material change in the basic and novel characteristics of the invention."). See also AK Steel Corp. v. Sollac, 344 F.3d 1234, 1240-41, 68 USPQ2d 1280, 1283-84 (Fed. Cir. 2003) (Applicant’s statement in the specification that "silicon contents in the coating metal should not exceed about 0.5% by weight" along with a discussion of the deleterious effects of silicon provided basis to conclude that silicon in excess of 0.5% by weight would materially alter the basic and novel properties of the invention. Thus, "consisting essentially of" as recited in the preamble was interpreted to permit no more than 0.5% by weight of silicon in the aluminum coating.); In re Janakirama-Rao, 317 F.2d 951, 954, 137 USPQ 893, 895-96 (CCPA 1963). If an applicant contends that additional steps or materials in the prior art are excluded by the recitation of "consisting essentially of," applicant has the burden of showing that the introduction of additional steps or components would materially change the characteristics of the claimed invention. In re De Lajarte, 337 F.2d 870, 143 USPQ 256 (CCPA 1964).”
The examiner has identified in para 38 that “the polypeptide variant of the Kunitz domain1 (KD1) of human tissue factor pathway inhibitor type2 that is disclosed herein further exhibits desirable and unexpected stability profile” appears to refer to the 60 amino acid sequence of SEQ ID NO:1, and not to longer peptides, and from para 52 that even coupling an additional molecule or agent to the 60 amino acid sequence of SEQ ID NO:1 is encompassed in “consisting essentially of.”
For the purposes of compact prosecution, the examiner interprets “consisting essentially of” as applied in the claims to instant SEQ ID NO:1 to require all of the amino acids of the 60 amino acid sequence of SEQ ID NO:1, clearly not to exclude the C-terminus -IEK (which the applied prior art Bajaj teaches its 60 amino acid very similar sequence to end in -IEK in order to provide a C-terminal lysine to further improve plasmin inhibition by virtue of binding to the lysine binding sites on plasminogen/plasmin) and not to include further amino acid additions at either terminus of the peptide corresponding to instant sequence of SEQ ID NO:1, however to allow for coupling of this to “additional molecules or agents such as imaging agents, particles, polymers, or other agents including those that facilitate polypeptide delivery to a certain in vivo location (e.g. antibodies, peptides and the like).”
Any disagreement with this interpretation should be made of record in applicant’s next response.
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 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.
Response to Arguments
Applicant's arguments filed 6/18/26 have been fully considered but they are not persuasive.
The examiner acknowledges claim amendments to remove “essentially”, however on consideration of the objective data and applicant’s arguments alleging unexpected results, is not persuaded.
While applicant alleges Baja patent application language “encompasses millions of different variations of the Bajaj peptides having millions of different functional profiles,” Baja nonetheless teaches and focuses on a double mutant that comprises two of the three modifications in the sequence instantly claimed.
The examiner does not dispute applicant’s assertions of improvements of the triple mutant, however on consideration of the data underlying these assertions, and given what would be expected from the respective teachings of the references, does not conclude that the differences are unexpected. Among other concerns, the examiner is concerned that the data in Table 4, page 66, uses “greater than” values that do no coincide as to expected multiples (>20,000 not a multiple of >3,000), suggesting different rather than a single experiment for all evaluated agents, and even if a single experiment, is not persuaded that the results are unexpected given what the references teach and suggest (see bolded full para below). Please also see Examiner’s Comments toward the end of the 3/19/26 Final Office action.
Claim(s) 1-3, 5-13, 15-17, 19 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over US PGPUB 20140288000, published 9/25/14, inventor Bajaj (Bajaj), in view of US 2008/0026998, published 1/31/08, Kisiel et al. (Kisiel).
Claim 1 is directed to a pharmaceutical composition comprising: a polypeptide consisting of the sequence: NAEICLLPLDTGPCKARLLRYYYDRYTQSCROFLYGGCEGNANNFYTWEACDDACWRIEK (SEQ ID NO: 1); and a pharmaceutically acceptable excipient.
Bajaj teaches “… in certain embodiments there are provided 60-amino acid (e.g., SEQ ID NO:5) and 63-amino acid plasmin-inhibiting polypeptides containing the L17R substitution (e.g., SEQ ID NO:6) and having carboxy-terminal lysine, which polypeptides are active as inhibitors of the plasmin active site and also bind to the lysine binding site(s) in the Kringle domain(s) of plasmin, thus providing two modes of inhibitory activity of plasmin (i.e., dual activity). … The 60-amino acid and 63-amino acid plasmin inhibiting polypeptides containing both the substitution at position 11 (e.g., SEQ ID NO:3, for instance, Y11T) and the substitution at position 17 (e.g., SEQ ID NO:3, for instance L17R) are even more potent plasmin inhibitors and are dually reactive by virtue of binding to the lysine binding sites on plasminogen/plasmin via C-terminal lysine,” para 119.
The particularly noted as being an even more potent plasmin inhibitor SEQ ID NO:3 has a sequence, which is 60 amino acids in length, that is very similar peptide to instant SEQ ID NO:1 below:
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The only difference is that the Bajaj SEQ ID NO:3 has an arginine at its position 17 rather than a lysine at the corresponding position of instant SEQ ID NO:1.
The level of ordinary skill in the art is high.
Kisiel teaches and claims "KD1 polypeptides" that are structurally equivalent to or structurally similar to the primary structure of the KD1 domain of Kunitz inhibitor human type 2 tissue factor pathway inhibitor (TFPI-2) (SEQ ID NO:2), as well as methods for making and using a KD1 polypeptide, para 8 and elsewhere.
As to modifications of particular amino acids, para 10 states in its entirety, “In another embodiment, the KD1 polypeptide is a "double mutant" KD1 polypeptide or a "multiple mutant" KD1 polypeptide. The term "multiple mutant" is inclusive of the term "double mutant" and signifies a plurality of mutations (i.e., two or more) relative to the wild-type KD1 sequence. The multiple mutant KD1 polypeptide consists of a primary structure that is similar to, and in some embodiments equivalent to, the primary structure of the wild-type KD1 domain of human tissue factor pathway inhibitor-2 (TFPI-2) (SEQ ID NO:2), or a biologically active subunit thereof, with the proviso that the polypeptide includes a lysine instead of arginine at position 24 (R24K) together with at least one of the following additional changes (mutations) with respect to the wild-type KD1 domain primary structure: an arginine instead of a leucine at position 26 (L26R); a threonine instead of a tyrosine at position 20 (Y20T); a glutamate or a tyrosine instead of an aspartate at position 19 (D19E or D19Y); and/or a glutamate or a lysine instead of a tyrosine at position 55 (Y55E or Y55K). The amino acid numbering is as defined for the wild-type KD1 amino acid sequence.” (emphases added)
The numbering used in Kisiel when converted to the instantly used numbering (this evidenced on page 8 of the 11/13/25 Non-final Office action so not repeated here) corresponds to Y11T/R15K/L17R, which are the three modifications in instant SEQ ID NO:1 from the corresponding portion of the wild type Kunitz domain sequence (see instant para 10 regarding Fig. 10, which states in part, “Residue 1 is numbered according to the BPTI-Kunitz domain numbering and corresponds to the amino acid 10 in the TFPI-2 Kunitz domain1 sequence”).
Given the explicit and specific teaching by Kisiel of a KD1 polypeptide mutant that comprises R15K (R24K by Kisiel’s numbering), a person of ordinary skill in the art, motivated to improve the SEQ ID NO:3 sequence of Bajaj, and observing that such sequence already comprises two of the three modifications in bold above (this of a very small set of alternatives when considering the non-bolded alternatives regarding positions 19 and 55), would have reasonably considered and evaluated a further-modified Bajaj SEQ ID NO:3 that as its further modification has the R15K (equivalent to Kisiel’s R24K). The rationale is to apply Kisiel’s teaching to the shorter Bajaj peptide of its SEQ ID NO:3 that already demonstrated improved characteristics to obtain a further improved peptide. There would have been a reasonable expectation of success given Kisiel’s teachings combined with those of Bajaj.
Bajaj, para 207, teaches “The present invention also relates in certain embodiments to pharmaceutical compositions containing the plasmin-inhibiting polypeptides that are disclosed herein. In one embodiment, the pharmaceutical composition comprises a plasmin-inhibiting polypeptide in a pharmaceutically acceptable excipient, carrier or diluent and in an amount effective to prevent or attenuate cancer progression or block metastasis, when administered to an animal, preferably a mammal, most preferably a human. In other embodiments, the pharmaceutical composition comprises a plasmin-inhibiting polypeptide in a pharmaceutically acceptable excipient, carrier or diluent and in an amount effective to treat a subject in need of inhibition of a plasmin activity, for instance, in a method comprising administering to the subject an effective amount of a plasmin-inhibiting polypeptide disclosed herein,” bold emphasis added.
Based on the above reasoning and prior art statements and teachings, claims 1 and 21 would have been obvious.
As to claim 2, Bajaj paras 214 and 215 which list inter alia preservative and agents to adjust tonicity.
As to claim 3, Bajaj para 215 including regarding agents to adjust tonicity and para 209 teaching inter alia intravenous route of administering.
Further supporting the rejections of claims 2 and 3, Kisiel para 53 teaches saline among its excipients, saline being able to adjust tonicity and also useful as an excipient for intravenous injection or infusion.
Accordingly, considering the bases for rejection of claim 1 and the above regarding claims’ 2 and 3 limitations, claims 2 and 3 would have been obvious and are rejected.
Given Bajaj’s extensive teaching of polynucleotides, paras 154-192, these paragraphs including teaching of preparing polynucleotides that encode polypeptides of the invention, overall pertaining to instant claim 5, para 176 regarding known fact of degeneracy of the coding, this pertaining to instant claim 6 in particular, in that any such degeneracy would be acknowledged to reasonably result in the same polypeptide, para 188 regarding regulatory sequences in vectors this pertaining to claim 7, para 189 teaching “host cell” this pertaining to claim 8, para 186 teaching “Suitable host cells include bacteria, mammalian cells, yeast and baculovirus systems,” this pertaining to claim 9, instant claims 5-9 are rejected as obvious given these extensive teachings in Bajaj and when also considering the bases for rejection of claim 1. Note also Bajaj claims 34-38 addressing very similar subject matter as claimed.
Instant claims 10-12, 15, 16, and 17 when considering Bajaj paras 4, 207-208, and Kisiel, paras 19, 20, 73, 79, which teach methods including to treat bleeding and inhibit fibrinolysis (and as to claim 17 see para 7 and also para 73), would have been obvious when also considering the bases for rejection of claim 1. There would have been a reasonable expectation of success given the teachings and examples of Bajaj and Kisiel.
As to claim 13, Bajaj teaches that its embodiments, including its polypeptides and polynucleotides encoding those polypeptides, which it teaches are plasmin-inhibiting so can reduce bleeding, can be administered to a subject in need of trauma surgery, paras 4, 9, 35, 232, rendering obvious claim 13 when also applying the bases for rejection of claims 1 and 12 from which claim 13 depends.
Claim 19 depends from claim 10 and states that the composition is disposed in a matrix.
Bajaj, para 229, does teach “embodiments also relate to an intravaginal shell or core drug delivery device suitable for administration to the human or animal female. The device may be comprised of the active pharmaceutical ingredient in a polymer matrix, surrounded by a sheath, and capable of releasing the plasmin-inhibiting polypeptide in a substantially zero order pattern on a daily basis similar to devices used to apply testosterone as described in PCT Published Patent No. WO 98/50016.”
Based on this teaching, it would have been obvious to apply the modified-by-Kisiel Baja SEQ ID NO:3 – the basis for claim 1’s rejection, in a matrix for a range of treatments to control or reduce bleeding. The motivation is to apply an agent known to reduce or control bleeding in a device or format comprising a matrix for more uniform release of the agent. There would have been a reasonable expectation of success given the disclosed uses of the polypeptides taught in Baja and Kisiel and the known properties of polymer matrices.
Accordingly, claim 19 would have been obvious.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over US PGPUB 20140288000, published 9/25/14, inventor Bajaj (Bajaj), in view of US 2008/0026998, published 1/31/08, Kisiel et al. (Kisiel), as applied above to claims 1, 10 and 12, and further in view of US 6294648, published 9/25/01, inventors Delaria et al. (Delaria).
The rejection of claims 1, 10, 12 and 13 are set forth above.
Claim 14 depends from claim 13 and specifies that the traumatic injury is traumatic brain injury.
Neither Bajaj nor Kisiel specify this.
The level of ordinary skill in the art is high.
Delaria teaches serine protease inhibitory activities of the Kunitz domain proteins, and specifically teaches that its Kunitz domain proteins may therefore be effective therapeutics include traumatic brain injury and stroke, para 25.
Based on the improved properties of the modified Kunitz domain (KD) polypeptides taught by Kisiel, it would have been obvious to substitute these for those of Delaria, with a reasonable expectation of success given the teachings of Bajaj and also of Kisiel including the advantages over aprotinin and single mutant versions of KD-based polypeptides (i.e., see para 179). The rationale is to substitute a known polypeptide having improved characteristics to treat a condition taught by others with a similar polypeptide.
Accordingly, claim 14 would have been obvious and is rejected under this section.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over US PGPUB 20140288000, published 9/25/14, inventor Bajaj (Bajaj) in view of US 2008/0026998, published 1/31/08, Kisiel et al. (Kisiel), as applied above to claims 1 and 12, and further in view of H. Paran et al. / The American Journal of Surgery 190 (2005) 463–466 (Paran, previously provided).
The rejection of claims 1 and 12 are set forth above.
The level of ordinary skill in the art is high.
Claim 18 depends from claim 12, which depends from claim 1, and claims that the bleeding is in a patient undergoing treatment for traumatic hemorrhagic shock.
This is not explicitly taught in Bajaj or Kisiel, although Kisiel does broadly teach that its polypeptides can advantageously be used to treat a subject for a condition treatable by aprotinin, and afford advantages over aprotinin, paras 19, 72, 73.
Paran, whose objective was to evaluate the effect of aprotinin in a model of uncontrolled intra-abdominal bleeding as a basis for its potential use in trauma patients, teaches that early administration of aprotinin resulted in temporary hemodynamic stabilization and prolonged survival in a model of uncontrolled bleeding, this bleeding being a model of uncontrolled hemorrhagic shock, Title, Objective, Conclusions.
Given the advantages of the Kisiel polypeptides over aprotinin as taught in Kisiel, it would have been obvious to substitute any of those polypeptides for the aprotinin Paran used to treat bleeding in a subject or patient undergoing treatment for traumatic hemorrhagic shock. There would have been a reasonable expectation of success given the similarities between aprotinin and the Kisiel polypeptides and the taught advantages of the Kisiel polypeptides over aprotinin, as taught by Kisiel, paras 19, 72, 73.
Accordingly, claim 18 is rejected as obvious.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over US PGPUB 20140288000, published 9/25/14, inventor Bajaj (Bajaj) in view of US 2008/0026998, published 1/31/08, Kisiel et al. (Kisiel), as applied above to claims 1, 10 and 19, and further in view of US PGPUB 20070255238, published 11/1/07, inventors Cochrum et al. (Cochrum).
The rejection of claims 1, 10 and 19 are set forth above.
Claim 20 depends from claim 19 and states, “wherein the matrix is a patch or compress.”
Neither Bajaj nor Kisiel explicitly teach claim 19’s “wherein the matrix is a patch or compress.”
The level of ordinary skill in the art is high.
Cochrum, however, teaches a hemostatic polymer useful for rapid blood coagulation and hemostasis, Title, and the specification teaches an “alternative embodiment [that] provides for a dry, removable storage stable, sterile wound dressing which provides a dry hemostatic zone, the dressing comprising a matrix containing a hemostasis-promoting amount of a therapeutic agent which accelerates blood coagulation and clot formation at an interface between a wound surface and a hemostatis promoting agent within the hemostatic zone,” paras 68, 98, see also Figures 5 and 7.
Cochrum also teaches that the matrix can be in the form of a patch, Fig. 6(A), paras 149, 154 and elsewhere.
Based on the rationale is to combine known products to achieve a more effective product claim 19 would have been obvious and is rejected under this section. There would have been a reasonable expectation of success given the known properties of the respective references.
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.
Response to Arguments
Applicant's arguments filed 6/18/26 have been fully considered but they are not persuasive. Applicant refers back to the arguments set forth against the above 35 USC 103 rejections, and the examiner’s response to these, above, is incorporated into this Response to Arguments.
Claims 1-3, 5-13, 15-17, 19 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, 9-11, 15, 18, 20, and 22 of U.S. Patent No. 7585842 (reference patent), in view of US PGPUB 20140288000, published 9/25/14, inventor Bajaj (Bajaj).
Claim 1 is directed to a pharmaceutical composition comprising: a polypeptide consisting of the sequence: NAEICLLPLDTGPCKARLLRYYYDRYTQSCROFLYGGCEGNANNFYTWEACDDACWRIEK (SEQ ID NO: 1); and a pharmaceutically acceptable excipient.
Reference patent claim 1, directed to variants and modifications of its SEQ ID NO:3, which is 73 amino acids in length, and sets forth modifications also found in instant claim 1’s SEQ ID NO:1, when combined with reference patent claim 3, which is directed to “The isolated polypeptide of claim 1 wherein the biologically active subunit of KD 1 is characterized by deletions of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid residues at either or both of the amino-terminal or carboxy-terminal end relative to the wild-type KD 1 sequence,” encompass a genus of polypeptides but do not explicitly claim a polypeptide consisting of instant SEQ ID NO:1, nor a pharmaceutical composition comprising this and a pharmaceutically acceptable excipient.
Bajaj, however, provides a motivation to focus within this genus to arrive at instant SEQ ID NO:1 while including some of the modifications of reference patent claim 1, by teaching “… in certain embodiments there are provided 60-amino acid (e.g., SEQ ID NO:5) and 63-amino acid plasmin-inhibiting polypeptides containing the L17R substitution (e.g., SEQ ID NO:6) and having carboxy-terminal lysine, which polypeptides are active as inhibitors of the plasmin active site and also bind to the lysine binding site(s) in the Kringle domain(s) of plasmin, thus providing two modes of inhibitory activity of plasmin (i.e., dual activity). … The 60-amino acid and 63-amino acid plasmin inhibiting polypeptides containing both the substitution at position 11 (e.g., SEQ ID NO:3, for instance, Y11T) and the substitution at position 17 (e.g., SEQ ID NO:3, for instance L17R) are even more potent plasmin inhibitors and are dually reactive by virtue of binding to the lysine binding sites on plasminogen/plasmin via C-terminal lysine,” para 119.
The particularly noted as being an even more potent plasmin inhibitor SEQ ID NO:3 has a sequence, which is 60 amino acids in length, that is very similar peptide to instant SEQ ID NO:1 below:
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The only difference is that the Bajaj SEQ ID NO:3 has an arginine at its position 17 rather than a lysine at the corresponding position of instant SEQ ID NO:1.
The level of ordinary skill in the art is high.
Reference patent claim 1 claims "KD1 polypeptides" that are structurally equivalent to or structurally similar to the primary structure of the KD1 domain of Kunitz inhibitor human type 2 tissue factor pathway inhibitor (TFPI-2) (SEQ ID NO:2), and claims modifications that primarily require (with other modifications in an “at least one” list of alternatives) “a lysine instead of arginine at position 24” (this based on different numbering, see above and page 8 of the 11/13/25 Non-final Office action, but indicating the same position as instantly referred to for position 17).
Considering the advantages of Bajaj’s 60 amino acid long SEQ ID NO:3 that differs from instant SEQ ID NO:1 only by has an arginine at its position 17 rather than a lysine, and reference patent claim 1 explicitly requiring this, it would have been obvious to further improve such polypeptides by providing a sequence falling within the genus of reference patent claim 1 but limited to 60 amino acids in length and conforming to Bajaj SEQ ID NO:3 with a further single modification to abide by reference patent claim 1’s primary requirement for modifications. There would have been a reasonable expectation of success in its performance given the combination of relevant teachings. Reference patent claim 9 claims “A pharmaceutical composition comprising: the isolated polypeptide of claim 1; and a pharmaceutically acceptable carrier,” Bajaj para 210 considers carriers to be encompassed by excipients, so this limitation of instant claim 1 also would have been obvious. Accordingly, claims 1 and 21 are rejected under this section.
As to claim 2, Bajaj paras 214 and 215 which list inter alia preservative and agents to adjust tonicity.
As to claim 3, Bajaj para 215 including regarding agents to adjust tonicity and para 209 teaching inter alia intravenous route of administering.
Accordingly, considering the bases for rejection of claim 1 and the above regarding claims’ 2 and 3 limitations, claims 2 and 3 would have been obvious and are rejected.
Given Bajaj’s extensive teaching of polynucleotides, paras 154-192, these paragraphs including teaching of preparing polynucleotides that encode polypeptides of the invention, overall pertaining to instant claim 5, para 176 regarding known fact of degeneracy of the coding, this pertaining to instant claim 6 in particular, in that any such degeneracy would be acknowledged to reasonably result in the same polypeptide, para 188 regarding regulatory sequences in vectors this pertaining to claim 7, para 189 teaching “host cell” this pertaining to claim 8, para 186 teaching “Suitable host cells include bacteria, mammalian cells, yeast and baculovirus systems,” this pertaining to claim 9, instant claims 5-9 are rejected as obvious given these extensive teachings in Bajaj and when also considering the bases for rejection of claim 1. Note also Bajaj claims 34-38 addressing very similar subject matter as claimed.
Instant claims 10-12, 15, 16, and 17 when considering Bajaj paras 4, 9, 35, 207-208, 232, and reference patent method claims 18, 20 and 22 including for treating a subject afflicted with hemophilia, claim 20, and per claim 22 in need of inhibition one activity of plasmin, would have been obvious when also considering the bases for rejection of claim 1. There would have been a reasonable expectation of success given the teachings and examples of Bajaj.
As to claim 13, Bajaj teaches that its embodiments, including its polypeptides and polynucleotides encoding those polypeptides, which it teaches are plasmin-inhibiting so can reduce bleeding, can be administered to a subject in need of trauma surgery, paras 4, 9, 35, 232, rendering obvious claim 13 when also applying the bases for rejection of claims 1 and 12 from which claim 13 depends.
Claim 19 depends from claim 10 and states that the composition is disposed in a matrix.
Bajaj, para 229, does teach “embodiments also relate to an intravaginal shell or core drug delivery device suitable for administration to the human or animal female. The device may be comprised of the active pharmaceutical ingredient in a polymer matrix, surrounded by a sheath, and capable of releasing the plasmin-inhibiting polypeptide in a substantially zero order pattern on a daily basis similar to devices used to apply testosterone as described in PCT Published Patent No. WO 98/50016.”
Based on this teaching, it would have been obvious to apply the modified-by-Kisiel Baja SEQ ID NO:3 – the basis for claim 1’s rejection, in a matrix for a range of treatments to control or reduce bleeding. The motivation is to apply an agent known to reduce or control bleeding in a device or format comprising a matrix for more uniform release of the agent. There would have been a reasonable expectation of success given the disclosed uses of the polypeptides taught in Bajaj and the known properties of polymer matrices.
Accordingly, claim 19 would have been obvious.
Claim 14 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, 9-11, 15, 18, 20, and 22 of U.S. Patent No. 7585842 (reference patent), in view of US PGPUB 20140288000, published 9/25/14, inventor Bajaj (Bajaj), as applied above to claims 1, 10, 12, and 13, and further in view of US 6294648, published 9/25/01, inventors Delaria et al. (Delaria).
The rejection of claims 1, 10, 12 and 13 are set forth above.
Claim 14 depends from claim 13 and specifies that the traumatic injury is traumatic brain injury.
Reference patent claims do not claim this, nor does Bajaj specify this.
The level of ordinary skill in the art is high.
Delaria teaches serine protease inhibitory activities of the Kunitz domain proteins, and specifically teaches that its Kunitz domain proteins may therefore be effective therapeutics include traumatic brain injury and stroke, para 25.
Based on the improved properties of the modified Kunitz domain (KD) polypeptides taught by Bajaj and the single required modification taught in claim 1 of reference patent, it would have been obvious to substitute the resultant polypeptide for those of Delaria, with a reasonable expectation of success given the teachings of Bajaj and including the advantages over aprotinin and single mutant versions of KD-based polypeptides (i.e., see para 179). The rationale is to substitute a polypeptide having improved characteristics to treat a condition taught by others with a similar polypeptide.
Accordingly, claim 14 would have been obvious and is rejected under this section.
Claim 18 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, 9-11, 15, 18, 20, and 22 of U.S. Patent No. 7585842 (reference patent), in view of US PGPUB 20140288000, published 9/25/14, inventor Bajaj (Bajaj), as applied above to claims 1 and 12, and further in view of H. Paran et al. / The American Journal of Surgery 190 (2005) 463–466 (Paran, previously provided).
The rejection of claims 1 and 12 are set forth above.
The level of ordinary skill in the art is high.
Claim 18 depends from claim 12, which depends from claim 1, and claims that the bleeding is in a patient undergoing treatment for traumatic hemorrhagic shock.
This is not explicitly taught in Bajaj or nor claimed in the reference patent claims.
Paran, whose objective was to evaluate the effect of aprotinin in a model of uncontrolled intra-abdominal bleeding as a basis for its potential use in trauma patients, teaches that early administration of aprotinin resulted in temporary hemodynamic stabilization and prolonged survival in a model of uncontrolled bleeding, this bleeding being a model of uncontrolled hemorrhagic shock, Title, Objective, Conclusions.
Given the teachings of Bajaj including precautions about aprotinin, paras 10, 11, also see Figs. 5 and 6, and the performance of its 60 amino acid long polypeptide, as further modified based on the required modification of reference patent claim 1, it would have been obvious to substitute the resultant polypeptide for the aprotinin Paran used to treat bleeding in a subject or patient undergoing treatment for traumatic hemorrhagic shock. There would have been a reasonable expectation of success given the teachings of Bajaj.
Accordingly, claim 18 is rejected as obvious.
Claim 20 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, 9-11, 15, 18, 20, and 22 of U.S. Patent No. 7585842 (reference patent), in view of US PGPUB 20140288000, published 9/25/14, inventor Bajaj (Bajaj), as applied above to claims 1, 10 and 19, and further in view of US PGPUB 20070255238, published 11/1/07, inventors Cochrum et al. (Cochrum).
The rejection of claims 1, 10 and 19 are set forth above.
Claim 20 depends from claim 19 and states, “wherein the matrix is a patch or compress.”
Neither Bajaj teaches nor reference patent claims claim 19’s “wherein the matrix is a patch or compress.”
The level of ordinary skill in the art is high.
Cochrum, however, teaches a hemostatic polymer useful for rapid blood coagulation and hemostasis, Title, and the specification teaches an “alternative embodiment [that] provides for a dry, removable storage stable, sterile wound dressing which provides a dry hemostatic zone, the dressing comprising a matrix containing a hemostasis-promoting amount of a therapeutic agent which accelerates blood coagulation and clot formation at an interface between a wound surface and a hemostatis promoting agent within the hemostatic zone,” paras 68, 98, see also Figures 5 and 7.
Cochrum also teaches that the matrix can be in the form of a patch, Fig. 6(A), paras 149, 154 and elsewhere.
Based on the rationale is to combine known products to achieve a more effective product claim 19 would have been obvious and is rejected under this section. There would have been a reasonable expectation of success given the known properties of the respective references.
Conclusion
No claim is allowed.
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/JOSEPH FISCHER/Primary Examiner, Art Unit 1658
