TISSUE MARKERS

DETAILED ACTION Notice of Pre-AIA or AIA Status The present application is being examined under the pre-AIA first to invent provisions. Status of Claims Claims 1-7, 9-12, 14-19, 22-28, 31-39, 42-48 are pending. Claims 16-19, 22-28, 31-33, 44-47 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-7, 9-12, 14-15, 34-39, 42-43, and 48 are hereby examined. Claim Objections Applicant is advised that should claim 1 be found allowable, claim 48 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim Rejections - 35 USC § 103 The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action: (a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a). Claims 1-3, 6-7, 9-12, 14, 34-35, 38, and 48 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over US 8,092,513 to Khosravi in view of US 20070207186 to Scanlon. PNG media_image1.png 187 404 media_image1.png Greyscale Regarding Claim 1, Khosravi discloses a tissue marker for implanting through a cannula into a target tissue at a target site (stent-graft marker 35 is shown coiled into the cannula 44 in Figure 5A), the tissue marker imageable by one or more imaging modalities (since the stent-graft marker is made from polymer and nitinol, it would be imageable in various modalities such as CT, ultrasound, MRI) and having a flexible polymer sheet (top layer 22’ shown in Fig. 4B made from PTFE, which is a flexible polymer, col. 7, lines 35-36), with a predetermined density, wherein the flexible polymer sheet is initially arranged within the cannula in a rolled configuration (as shown by rolled marker element 35 in cannula 44 in Figure 5A and Figure 2A), constrained by the cannula from unrolling (constrained by cannula 44 in Figure 5A and Figure 2A), and, upon the implantation of the tissue marker at the target site, the flexible polymer sheet at least partially unrolls (the cannula is removed and the marker 35 unwinds to confirm to the diameter of the body lumen, col. 9, lines 5-18 and Figure 2B), with the flexible polymer sheet maintaining the predetermined density in both rolled and at least partially unrolled configurations (no swelling or shrinkage of the materials of the marker occur, i.e. it is not a hydrogel, so the density is unchanged). Khosravi further discloses wherein the tissue marker further comprises a shape-memory element carried by the flexible polymer sheet (element 21 in Figure 4B is a stent made from shape-memory alloy wires, col. 5, lines 34-35, col. 6, lines 31-43; interwoven wires col. 6, lines 5-10). Khosravi further discloses wherein the flexible polymer sheet comprises a contrast agent, detectable by at least one of the one or more imaging modalities (element 21 in Figure 4B is a stent made from shape-memory alloy wires including nickel-titanium alloy, col. 5, lines 34-35 and is embedded within the flexible polymer sheet; nickel-titanium alloy is a metal material and acts as a contrast agent for at least X-ray imaging). However, Khosravi does not teach wherein the contrast agent comprises iron oxide particles. In the same field as Khosravi, Scanlon teaches a stent-graft that is capable of use as a tissue marker, wherein two polymer layers sandwich a shape-memory element (Figure 7). Within the polymer layer 12, additives are incorporated including iron oxide particles (par. 0217) in order to achieve the desired imaging characteristics. One of ordinary skill in the art at the time of the invention would have found it obvious to provide iron oxide particles in the marker of Khosravi in order to achieve the desired characteristics such as imaging contrast (to increase radiopacity) as in Scanlon. Regarding Claim 2, Khosravi further discloses wherein the flexible polymer sheet is capable of defining a hollow cylinder in the rolled configuration (as in Fig. 2A and 5A, the marker is rolled into a cylinder shape which has a hollow part near the center). Regarding Claim 3, Khosravi further discloses wherein the flexible polymer sheet is capable of fully unrolling to form a planar shape (For claim interpretation, the flexible polymer sheet is only required to be capable of fully unrolling to form a planar shape. The claim does not specify the conditions that causes the unrolling to occur. The rolled marker 35 of Khosravi is capable of fully unrolling, e.g. by hand or by expansion of the balloon as shown in Figure 5B, and would have a planar shape in such a fully unrolled configuration, i.e. a flat piece, as shown in Fig. 3 and Fig. 4D; as such, Khosravi inherently teaches the ability of being capable of fully unrolling to form a planar shape per MPEP 2114(I).). Regarding Claim 6, Khosravi further discloses wherein the one or more imaging modalities are selected from a group consisting of ultrasound imaging, X-ray-based imaging, magnetic resonance imaging (MRI), fluorescent imaging, and any combinations thereof (col. 9, lines 12-13 specifically state fluoroscopy and standard angiography which are both X-ray based imaging procedures; further the marker of Khosravi is capable of being imaged by at least ultrasound and MRI due to it being made of materials that are visible by those imaging modes, i.e. nitinol wires, polymer; especially when considered in combination with Scanlon to include the iron oxide particles, this would make it highly MRI-visible). Regarding Claim 7, Khosravi further discloses wherein the flexible polymer sheet in the at least partially unrolled configuration is capable of conforming to a void at the target site (conforms to the diameter of the body lumen, col. 9, lines 16-18), wherein the target site is a soft tissue selected from the group consisting of breast tissue, colon tissue, rectal tissue, ovarian tissue, prostate tissue, and lung tissue (Khosravi teaches variability of the size of the stent-graft to accommodate the desired tissue scale (col. 3, lines 55-57). Further, the size range disclosed, e.g. to accommodate the coronary arteries or abdominal aorta, of the stent-grant of Khosravi is capable of use in other tissues as an implanted marker. For example, a stent-graft sized for coronary arteries would be capable of marking soft tissues in the breast or liver.). Regarding Claim 9, Khosravi further discloses wherein the shape-memory element comprises a curved wire (element 21 in Figure 4B is a stent made from shape-memory alloy wires, col. 5, lines 34-35, col. 6, lines 31-43; interwoven wires col. 6, lines 5-10; the wires of element 21 implicitly curve when in the rolled configuration Figure 2A or partially unrolled configuration Figure 2B). Regarding Claim 10, Khosravi further discloses wherein the shape-memory element comprises a coil (when in the rolled configuration Figure 2A or partially unrolled configuration Figure 2B, the shape-memory element is considered coiled and therefore a coil). Regarding Claim 11, Khosravi further discloses wherein the flexible polymer sheet comprises first and second layers (top layer 22’ shown in Fig. 4B made from PTFE, col. 7, lines 35-36, and a second layer, bottom layer 22’ shown in Figure 4B made from PTFE, col. 7, lines 35-36) and the shape-memory element is located between the first and second layers (element 21 in Figure 4B is sandwiched between the layers). Regarding Claim 12, Khosravi further discloses wherein the shape-memory element is a material selected from the group consisting of copper-aluminum-nickel alloys, nickel-titanium alloys, and combinations thereof (element 21 in Figure 4B is a stent made from shape-memory alloy wires including nickel-titanium alloy, col. 5, lines 34-35). Regarding Claim 14, Khosravi further discloses wherein the contrast agent is selected from a group consisting of metal oxide particles, metal materials, amorphous materials, crystalline materials, has bubbles, paramagnetic substances, and any combinations thereof (element 21 in Figure 4B is a stent made from shape-memory alloy wires including nickel-titanium alloy, col. 5, lines 34-35, which is a metal material). Regarding Claim 34, Khosravi further discloses wherein the X-ray based imaging is computed tomography (the stent-graft is viewable in a computed tomography image by virtue of its materials being made of metal). Regarding Claim 35, Khosravi further teaches wherein the predetermined density of the flexible polymer sheet differs by no more than 30% from the target tissue (Examiner notes that the target tissue has not been defined by the claim and at least a portion of the polymer sheet of Khosravi is formed of PTFE, which implicitly has a density within 30% as that of harder tissues. Applicant also lists PTFE as a suitable material choice for the marker in par. 0033. Examiner is giving the claim its broadest reasonable interpretation in light of the disclosure.). Regarding Claim 38, Khosravi further teaches wherein the implantable marker is configured to migrate less than 10 mm from the target site over a period of at least one month from the target site upon the implantation of the implantable tissue marker at the target site (this is an inherent characteristic of the device of Khosravi since it is utilized as a stent-graft marker implanted into a blood vessel which is configured not to migrate, as tissue ingrowth into the graft layer occurs during implantation; since the materials and size of Khosravi’s device are similar to that of Applicant’s, it is expected to inherently act the same way when implanted and therefore migrate very little, i.e. less than 10 mm in a month). Claim 48 is substantially the same as Claim 1 and therefore rejected for the same reasons. Claims 4-5, 36-37 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over US 8,092,513 to Khosravi in view of US 20070207186 to Scanlon, as applied to claim 1 above, and in further view of US 20090030502 to Sun. Regarding Claims 4-5, Khosravi does not expressly teach the sheet comprising “macropores forming an interconnected network of pores within the flexible polymer matrix” or “macropores penetrate through the entire thickness of the flexible polymer sheet” when applied to the embodiment of Figure 4B. However, Khosravi teaches layers 22’ of Fig. 4B are made of thermoplastic biocompatible graft material, such as PTFE (col. 7, lines 32-46). Khosravi also teaches in alternate embodiments, polyester fiber is an appropriate selection for the material of the graft layer (Fig. 3 layer 22, PTFE or polyester fabric, col. 6, line 66 – col. 7, line 6). Based on the teachings of Khosravi, one of ordinary skill in the art at the time of the invention would have found it obvious to utilize the polyester fiber as the layer 22’ of Fig. 4B since Khosravi recognizes polyester fiber as a suitable biocompatible graft layer (i.e. functionally equivalent) and one of ordinary skill would recognize both PTFE and polyester as thermoplastics (i.e. layers fuse together when heated). As such, only expected results would occur to utilize polyester fabric as a routine matter of design choice. Sun teaches an imageable stentgraft wherein a polymer sheet is layered onto wires (e.g. as shown in Figure 8 and throughout the specification). Sun further teaches wherein the polymer sheet is made of woven polyesters such as DACRON which possess varying degrees of porosity, which are selectively controlled based on the weaving or knitting process. The porosity is made to encourage incorporation of a patient’s tissue into the woven graft material, which more securely anchors the implant. The porosity can be loose to allow fluids to flow through or tight to prevent fluids to flow through (par. 0029). As such, Sun implicitly teaches “pores penetrating through the entire thickness of the sheet” since fluids can flow through the pores in the weave. Further, the pores of Sun are considered to be an “interconnected network” because they are created by an interconnected weave pattern and organized into a patterned mesh network. As such, one of ordinary skill in the art at the time of the invention would have found it obvious to include the penetrating pores through the thickness of the woven sheet in a woven interconnected network in Khosravi as taught by Sun to be beneficial for encouraging tissue to incorporate into the implant, thereby improving anchoring of the implant while still permitting some fluid flow. Regarding Claim 36, Khosravi in view of Sun further teaches wherein the macropores penetrate through both opposing surfaces of the flexible polymer matrix, for the same reason as in claim 1 above. Regarding Claim 37, Khosravi in view of Sun further teaches wherein the macropores have a dimension sufficient for at least one cell to reside therein (the pores are for the purpose of tissue ingrowth, thereby cells are capable of residing therein, par. 0029 of Sun). Claim 39 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over US 8092513 to Khosravi in view of US 20070207186 to Scanlon and, in the alternative, over US 8092513 to Khosravi in view of in view of US 20070207186 to Scanlon , as applied to claim 1 above, in further view of WO 2008/007048 to Ashton. Regarding Claim 39, Khosravi teaches changing the size of the sheet width based on the intended anatomy site (e.g. 2-4 cm diameter for larger arteries (6.28-12.56cm width, i.e. circumference), 8-12 mm diameter for medium size arteries (2.51-3.77 cm width, i.e. circumference), col. 6, lines 44-59). Examiner is interpreting “width” of the sheet as in the unrolled configuration (perpendicular to the rolling direction) of which is equivalent to the circumference in the partially unrolled configuration. In the same field as Khosravi, Scanlon teaches a stent-graft that is capable of use as a tissue marker, wherein two polymer layers sandwich a shape-memory element (Figure 7). Scanlon further teaches wherein the diameter of the stent-graft is within the range of 0.5 mm to 60 mm diameter (i.e. 0.157 cm – 18.84 cm width or circumference) (par. 0304) and for smaller neurological applications the diameter is about 2 mm (i.e. 0.63 cm width or circumference) (par. 0305). Scanlon further teaches for larger blood vessels the diameter is 30 mm (i.e. 9.42 cm width or circumference) (par. 0305), just like Khosravi. As taught by both Khosravi and Scanlon, adjusting the width (which is related to circumference of the blood vessel where it is to be implanted) is well within routine design choice for one of ordinary skill in the art at the time of the invention and only expected results would occur to size the implant to the blood vessel. Further, the range of 0.157 cm – 18.84 cm expressly taught by Scanlon overlaps with the claimed range of 0.2 to 1.5 cm. For the alternative limitation in Claim 39 (“or wherein the flexible polymer sheet has a thickness of 0.05 mm to 4 mm”), Khosravi further suggests wherein the flexible polymer matrix has a thickness of 0.05mm to 4mm (coiled sheet portion 21 is between 1.0 to 5.0 mils thick (0.0254 mm to 0.127 mm) col. 5, lines 58-60, it is inferred from Figure 4B that the two layers 22’ together are less than the thickness of the coiled portion 21 and the total thickness of the flexible polymer matrix at the point of the wire must be within the claimed range, e.g. 0.127 mm + <0.127mm must be within the range 0.127-0.254 mm). However, since drawings are not always drawn to scale, additional evidence is provided to teach the claimed range. Similar to Khosravi, Ashton teaches a stent-graft with shape-memory material sandwiched between flexible polymer matrix layers of graft material (nitinol material 4a, 4b, 4c as in Figure 2 is sandwiched between polymer graft layers 2 and 1; page 13, second paragraph; page 8, fourth paragraph). Ashton further teaches wherein the thickness of the outer polymer graft layer is between 0.05 mm to 0.5 mm (page 11, second paragraph; page 14, last paragraph) and the thickness of the inner polymer graft layer is 0.12 mm thickness (page 14, last paragraph). That gives the range of the total sheet (both layers added together) of 0.17 mm to 0.62 mm, which is within the claimed range of 0.05 mm to 4 mm. Using the same thickness of polymer layers of Ashton in Khosravi’s device, even in areas with the nitinol wire, the thickness would increase by 1.0-5.0 mils (0.0254 mm to 0.127 mm) and still be well within the claimed range. One of ordinary skill in the art at the time of the invention would have found it a routine matter of design choice to utilize the thickness of polymer graft as in Ashton as the thicknesses of the polymer graft layers of Khosravi because a reasonable expectation of success is expected to occur. The motivation would be to suitably function as an imageable stent-graft marker. Terminal Disclaimer The terminal disclaimer filed on August 1, 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of application 16108525 and patent 12310800 has been reviewed and is accepted. The terminal disclaimer has been recorded. Allowable Subject Matter Claims 42-43 are objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. In particular, the prior art does not teach or suggest the “single wire” configuration of claim 42 in combination with intervening limitations of claim 1. Examiner interprets this limitation as precluding any other wires, thereby consisting of a single wire for the shape-memory element. US 8092513 to Khosravi teaches a plurality of wires, thereby permitting it to act as a stentgrant mesh. It would not be obvious to remove the wires to reduce to only one wire because it would dramatically change the structural properties of the Khosravi stentgrant marker device. US 20060116709 to Sepetka teaches an imageable marker that rolls in a pre-deployed configuration (Figure 13B) and unrolls in a deployed configuration (Figure 13A). The marker comprises a radiopaque wire sewn into a polymer sheet (par. 0071) but there is no suggestion of using a single wire. Rather, multiple wires are shown diagonally and also around the perimeter. Reducing to only one wire would not be obvious since it would change the structural properties of the device. Response to Arguments Applicant’s arguments filed June 22, 2026 with respect to the restriction requirement have been considered but are moot because Applicant has amended the claims to revert to the originally examined invention. Applicant's arguments regarding the prior art rejection have been fully considered but they are not entirely persuasive. Applicant argues that the Office has not met burden of obviousness because it was not described how to select “iron oxide” particles from the list of over 650 additives from par. 0217 of Scanlon or how Scanlon specifically mentions that such iron oxide particles can be used in order to achieve the desired imaging characteristics. However, Scanlon teaches the “additives” are just that – they are added to the material to achieve the desired “magnetic signal characteristics” (par. 0217). Iron oxide particles are extremely common in the imaging arts to add to a substance to give it increased contrast for MRI procedures, as recognized by one of ordinary skill in the art. Scanlon need not teach this benefit expressly, Examiner may rely on level of one of ordinary skill in the art. Obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). Applicant further argues that the limitation of “the shape-memory element is a single wire” is not taught by the references. In combination with the other features of claim 1, Examiner agrees and has indicated claims 42-43 as avoiding the prior art. Conclusion 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 ANGELA MARIE HOFFA whose telephone number is (571)270-7408. The examiner can normally be reached Monday - Friday 9:30 am - 6:00 pm. 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, Keith Raymond can be reached at (571)270-1790. 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. ANGELA M. HOFFA Primary Examiner Art Unit 3799 /Angela M Hoffa/Primary Examiner, Art Unit 3799