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 the Claims
Applicant’s submission filed 05 December 2025 has been entered. Claims 9-10 and 12-28 are pending. Claims 9, 19, 21, and 25-28 have been amended, while claim 11 has been cancelled without prejudice or disclaimer. Therefore, prosecution on the merits continues for claims 9-10 and 12-28. All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Objection to claims 9, 19, 21, and 25-28
Applicant’s amendments to each of claims 9, 19, 21, and 25-28 correct the minor informalities present within each claim, thus obviating the objections of record.
Therefore, the objections are withdrawn.
RE: Rejection of claims 9-10, 15-16, 19-23, and 25-26 under 35 USC 102(a)(1) over Atsushi et al
Applicant has amended independent claims 9, 21, and 26 to incorporate the limitation from now cancelled claim 11, wherein the inner diameter of the cylindrical hollow construct is 50% or less of the outer diameter of the inner cylindrical hollow construct. As instant claim 11 was not included within the rejection of record, the amendment obviates the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 9-12, 15-16, and 18-28 under 35 USC 103 over Atsushi et al in view of Mitsuhiro et al*
*The Examiner apologizes for incorrectly citing Mitsuhiro et al (JP2009253313A) as the reference of record, as the Examiner accidentally entered the priority Japanese application number instead of the publication number into the PTO-892 Notice of References Cited form. Therefore, the attached reference is actually Japanese publication number JP2011097850A, which is hereinafter referred to as Kuzo et al. The Examiner has reattached Kuzo et al – which again is the same reference provided and cited to within the Office action filed 05 September 2025 – with the appropriate publication number on the PTO-892 Notice of References Cited form.
Applicant's arguments filed 05 December 2025 have been fully considered but they are not persuasive.
Applicant has traversed the rejection, asserting in Pages 8-9 of the Remarks filed 05 December 2025 that Kuzo et al fail to disclose the relationship between the outer diameter and inner diameter of the ameroid ring itself, as Kuzo et al instead disclose ameroid rings that have an inner diameter that is 62.5% of the vessel outer diameter. In response, the Examiner respectfully submits that the ordinary artisan would have recognized that an ameroid ring clamped around a vessel will have a similar effect to a shunt tube inserted within vessel, as they both allow for the constriction or minimizing of the vessel wall diameter. More specifically, when situated and clamped around the vessel, an ameroid ring having an inner diameter of 1.25 mm will constrict the vessel – which has an outer diameter of 2 mm – such that the outer diameter of the vessel is now 1.25 mm. When translated to a shunt tube, the shunt tube inserted within the vessel will have an outer diameter of 2 mm – or whatever size is necessary to fit the inner diameter of the artery – and an inner diameter that is 1.25 mm. Therefore, the relationship between the inner diameter and outer diameter of the ameroid ring in Kuzo et al is inconsequential, as the functional effect that is translatable to the shunt tube is dependent upon the inner diameter of the ameroid ring and the outer diameter of the vessel.
Applicant has further traversed the rejection, asserting in Pages 9-12 of the Remarks filed 05 December 2025 that the insertion of hollow constructs having an inner diameter that is 10-40% of the outer diameter into the left anterior descending artery of porcine models are critical and led to unexpected results, including substantial coronary narrowing over time, a severe but chronic reduction in ejection fraction, histopathology confirmed necrosis, collagen deposition, and hypoxia in the myocardium, and a significantly improved survival rate compared with conventional methods. Applicant supports these assertions with Tables 1-3 and Examples 2-5 of the instant disclosure. In response, the Examiner respectfully submits that MPEP § 2144.05 states that a prima facie case of obviousness exists when a range or value overlaps with or is merely close to the claimed range or value, particularly in the absence of evidence the claimed range yields critical or unexpected results. The claimed range is “wherein the inner diameter of the cylindrical hollow construct is 50% or less of the outer diameter of the cylindrical hollow construct”. Applicant has instead asserted that the critical values are 10-40%, although the Examiner notes that the hollow constructs presented in Table 1 and utilized within the Examples of the instant disclosures have inner diameters that are approximately 14%, 12.5%, and 28% of the outer diameter. Regardless, the range of diameter ratios having the critical and unexpected results is much narrower than the claimed range. Therefore, Applicant has not provided evidence that the claimed range yields critical or unexpected results.
The Examiner also respectfully reminds Applicant that, in submitting evidence asserted to establish unobvious results, there is a burden on Applicant to indicate how the examples asserted to represent the claimed invention are considered to relate to the examples intended to represent the prior art and, particularly, to indicate how those latter examples do represent the closest prior art. The evidence relied upon should also be reasonably commensurate in scope with the subject matter claimed and illustrate the claimed subject matter relative to the prior art subject matter. See MPEP § 2145. It should also be established that the differences in the results are in fact unexpected and unobvious and of both statistical and practical significance. See MPEP § 716.02(b). In the instant case, Applicant has failed to indicate how the alleged unexpected results differ from the closest prior art, and instead compares the five-week survival rate to conventional balloon-catheter models.
Therefore, the rejection is maintained and amended to encompass the claims as written.
RE: Rejection of claims 9-10, 15-16, 19-23, and 25-26 under 35 USC 103 over Atsushi et al in view of Miller et al
Applicant has amended independent claims 9, 21, and 26 to incorporate the limitation from now cancelled claim 11, wherein the inner diameter of the cylindrical hollow construct is 50% or less of the outer diameter of the inner cylindrical hollow construct. As instant claim 11 was not included within the rejection of record, the amendment obviates the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 9-10, 14-16, 19-23, and 25-26 under 35 USC 103 over Atsushi et al in view of Rissanen et al
Applicant has amended independent claims 9, 21, and 26 to incorporate the limitation from now cancelled claim 11, wherein the inner diameter of the cylindrical hollow construct is 50% or less of the outer diameter of the inner cylindrical hollow construct. As instant claim 11 was not included within the rejection of record, the amendment obviates the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 9-10, 15-17, 19-23, and 25-26 under 35 USC 103 over Atsushi et al in view of Levine et al
Applicant has amended independent claims 9, 21, and 26 to incorporate the limitation from now cancelled claim 11, wherein the inner diameter of the cylindrical hollow construct is 50% or less of the outer diameter of the inner cylindrical hollow construct. As instant claim 11 was not included within the rejection of record, the amendment obviates the rejection of record.
Therefore, the rejection is withdrawn.
New/Maintained Grounds of Rejection
Claim Interpretation
Instant claim 9 is directed to a method for inducing myocardial infarction of an animal, comprising preparing a cylindrical hollow construct with a through-hole extended in a longitudinal direction, … by 3-dimensional printing of a polymer melt. This is a product-by-process limitation. Product-by-process limitations are considered only in so far as the method of production affects the structure of the final product. In the instant case, there is no evidence that the 3-dimensional printing of the cylindrical hollow construct imparts any particular structure or significance to the composition other than the cylindrical hollow construct being comprised of a polymer. Thus, the claim will be interpreted as if a polymeric cylindrical hollow construct derived from any production method fulfills the recited claim limitation.
Instant claims 10-20 depend from instant claim 9 and thus incorporate this interpretation as well.
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 9-10, 12, 15-16, and 18-28 are rejected under 35 U.S.C. 103 as being unpatentable over Atsushi et al (JP2015057984A, translation provided by Global Dossier, of record) in view of Kuzo et al (JP2011097850A, translation provided by Global Dossier, of record).
Atsushi et al and Kuzo et al are each considered prior art under 35 USC 102(a)(1).
Regarding claims 9-10, 12, 20-23, 26: The instant claim comprises a product-by-process limitation that is interpreted as set forth in the Claim Interpretation section above.
Atsushi et al disclose a method for producing an ischemic animal model, and an ischemic animal model obtained thereby (Paragraph [0001]).
As such, Atsushi et al disclose a method of modeling myocardial infarction in a pig, wherein a polyvinyl chloride shunt tube is inserted into the left anterior descending coronary artery of the pig (Paragraphs [0010], [0013]-[0016], [0021]; Figure 1). Atsushi et al further disclose that the shunt tube is sized to fit the inner diameter of the artery and has an inner diameter of a certain size that allows for the passage of blood flow (Paragraph [0015]).
Atsushi et al fail to disclose that the inner diameter of the shunt tube is 50% or less of the outer diameter of the shunt tube, as required by instant claims 9, 21, and 26.
Kuzo et al, however, disclose methods for producing animal models of myocardial infarction (Paragraph [0001]).
As such, Kuzo et al disclose constricting the left anterior descending artery of a porcine model with an ameroid ring that has an inner diameter that is 0.75 mm smaller than the outer diameter of the artery, wherein the outer diameter of the artery is 2.0 mm (Paragraphs [0011], [0019], [0022], [0024], [0033]). Kuzo et al further disclose that the ameroid ring has a length of 3.5 mm (Figure 1).
Therefore, it would have been prima facie obvious to modify the shunt tube of Atsushi et al such that the inner diameter of the tube is about 50% of the outer diameter, as detailed in Kuzo et al. One of ordinary skill in the art would have been motivated to mimic the constriction of the artery via the ameroid ring with the shunt tube, as it allows for the simple modeling of myocardial infarction within the animal with minimal risks of killing the model within 5 weeks (Paragraphs [0011], [0018], [0020], [0033]; Table 2; Figure 3), and would have had a reasonable expectation of success since Atsushi et al disclose that the shunt tubes can have a variety of sizes (Paragraph [0013], [0015], [0019]). See MPEP § 2143(I)(G).
Consequently, Atsushi et al as modified by Kuzo et al render obvious a method of modeling myocardial infarction in a pig (claims 20, 22), wherein a polyvinyl chloride – or polymeric – shunt tube is inserted into the left anterior descending coronary artery of the pig (claims 10, 23). As the shunt tube is sized to fit the inner diameter of the artery – or has an outer diameter that is 100% of an inner diameter of the left anterior descending coronary artery – and has an inner diameter that is about 50% of the outer diameter of the tube and a length of 3.5mm (claim 12), this therefore renders obvious the methods of instant claims 9 and 26 and animal model of instant claim 21 derived therefrom.
It is of note that a prima facie case of obviousness exists when a range or value overlaps with or is merely close to the claimed range or value, particularly in the absence of evidence the claimed range yields critical or unexpected results. See MPEP § 2144.05. More specifically, this pertains to the inner diameter of the shunt tube rendered obvious by Atsushi et al and Kuzo et al, as 62.5% (1.25mm/2.00mm) is merely close to 50%.
Regarding claims 15-16: Following the discussion of claim 9, the method disclosed by Atsushi et al does not include the removal of the shunt tube from the left anterior descending coronary artery of the pig (Paragraphs [0010], [0013]-[0016], [0021]; Figure 1). This therefore reads on the methods of the instant claims.
Regarding claims 18 and 24: Following the discussion of claims 9 and 21, Kuzo et al disclose that the survival rate of the porcine models after 5 weeks is 100% in the three minipigs having arteries constricted by about 50% (Paragraph [0033]; Table 2). This therefore renders obvious the method of instant claim 18 and animal model of instant claim 24 for the same reasons as discussed in the rejection of instant claims 9 and 21.
Regarding claims 19 and 25: Following the discussion of claims 9 and 21, Atsushi et al further disclose that the pigs comprising the implanted shunt tube experienced extensive tissue necrosis in the left ventricle wall of the heart (Paragraph [0023]; Figure 3). This therefore reads on the method of instant claim 19 and animal model of instant claim 25.
Regarding claim 27-28: Following the discussion of claim 21, Atsushi et al further disclose that the hallmark features of myocardial infarction include a decrease in the flow rate of blood, ischemic myocardium, and necrotic tissue (Paragraph [0003]).
With that, Kuzo et al further disclose that the porcine models of myocardial infarction can be utilized for the development of therapeutic drugs for chronic myocardial infarction and for myocardial regenerative medicine research (Paragraphs [0002], [0012], [0020], [0039]).
Therefore, it would have been prima facie obvious to have modified by the animal model of Atsushi et al such that it is utilized in the screening of therapeutic drugs for the treatment of chronic myocardial infarction, as reasonably suggested in Kuzo et al. One of ordinary skill before the effective filing date of the invention would have been motivated to test candidate therapeutics that alleviate the associated symptoms of myocardial infarction – including the increase of blood flow and reversal of the necrotic tissue – on a more anatomically accurate model of myocardial infarction in humans (Atsushi et al: Paragraph [0016]; Kuzo et al: Paragraph [0022]), and would have had a reasonable expectation of success since the disclosures of Atsushi et al and Kuzo et al are both concerned with the generation of a porcine model of myocardial infarction via the occlusion of the left anterior descending coronary artery. See MPEP § 2143(I)(G).
Consequently, Atsushi et al as modified by Kuzo et al render obvious a method of screening candidate therapeutics for the treatment of myocardial infarction, wherein a candidate therapeutic is administered to the porcine model of myocardial infarction to alleviate the necrosis of the left ventricle wall of the heart within the pigs (claim 28). This therefore renders obvious the method of instant claim 27.
Claims 9-10, 12-13, 15-16, and 18-28 are rejected under 35 U.S.C. 103 as being unpatentable over Atsushi et al (JP2015057984A, translation provided by Global Dossier, of record) in view of Kuzo et al (JP2011097850A, translation provided by Global Dossier, of record), and further in view of Miller et al (US 2017/0095257 A1, of record).
The discussion of Atsushi et al in view of Kuzo et al regarding claim 9 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Atsushi et al as modified by Kuzo et al render obvious claims 9-10, 12, 15-16, and 18-28. Miller et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claim 13: As aforementioned in the discussion of claim 9, Atsushi et al disclose that the shunt tube is comprised of polyvinyl chloride.
Atsushi et al further disclose that the shunt tubes can be made from a variety of materials (Paragraphs [0013], [0015], [0019]).
The combination of Atsushi et al and Kuzo et al fail to teach that the polymer is one or more selected from the group consisting of polycaprolactone (PCL), poly(lactate-co-glycolate) (PLGA), poly lactic acid (PLA), polyurethane (PU), poly(lactide-co-caprolactone) (PLCL), polydioxanone (PDO), polystyrene (PS), poly(ethylene glycol) (PEG), poly(vinyl acetate) (PVA), polypropylene glycol (PPG), polyacrylamide (PAAm), polyglycolic acid (PGA), polymethylmethacrylate (PMMA), polyhydroxybutyrate (PHB), and polyvinylpyrrolidone (PVP), as required by instant claim 13.
Miller et al, however, disclose devices for occluding arteries, wherein the occluder is a single-piece device with a hollow center that is made of PGA, poly-L-lactide, PLGA, or PDO (Abstract; Paragraphs [0094], [0104], [0138]).
Therefore, it would have been prima facie obvious to have substituted the polymer in which the shunt tube is made of from polyvinyl chloride to one of PGA, PLA, PLGA, or PDO, as doing so would have been a simple substitution of one known occluder polymer for another. See MPEP § 2143(I)(B). One of ordinary skill in the art would have recognized that the polymers are functionally comparable, as both are biocompatible polymers that are inserted into the body of animal models for the occlusion of arteries, and thereby would have been able to substitute the polymers with predictable results.
Consequently, Atsushi et al as modified by Kuzo et al and Miller et al render obvious a method of generating an animal model of myocardial infarction, wherein a shunt tube made of PGA, PLA, PLGA, or PDO is inserted into the left anterior descending coronary artery of the animal. This therefore renders obvious the method of the instant claim.
Claims 9-10, 12, 14-16, and 18-28 are rejected under 35 U.S.C. 103 as being unpatentable over Atsushi et al (JP2015057984A, translation provided by Global Dossier, of record) in view of Kuzo et al (JP2011097850A, translation provided by Global Dossier, of record), and further in view of Rissanen et al (Am J Physiol Heart Circ Physiol, 2013, of record).
The discussion of Atsushi et al in view of Kuzo et al regarding claim 9 can be observed above and
is relied upon herein, the content of which is incorporated in its entirety. Atsushi et al as modified by Kuzo et al render obvious claims 9-10, 12, 15-16, and 18-28. Rissanen et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 14: Following the discussion of claim 9, Atsushi et al further disclose that the shunt tube is directly inserted into the left anterior descending artery following the exposure of the porcine hearts via median thoracotomy (Paragraph [0022]).
The combination of Atsushi et al and Kuzo et al fail to teach that the shunt tube is implanted into the left anterior descending artery via the carotid artery, as required by instant claim 14.
Rissanen et al, however, disclose the implantation of a stent within the left anterior descending artery of a porcine model of myocardial infarction (Pages H1297-H1298; Figure 1). Rissanen et al further disclose that it is well known in the art that surgical dissection of the carotid artery is often utilized for coronary arterial access in pigs (Page H1298).
Therefore, it would have been prima facie obvious to have modified the method of Atsushi et al in view of Kuzo et al such that the shunt tube is implanted into the porcine model through the carotid artery, as reasonably suggested by Rissanen et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to utilize an implantation route that is well-known in the art, and would have had a reasonable expectation of success since the disclosures of both Atsushi et al and Rissanen et al are concerned with the occlusion of the left anterior descending artery as a model of myocardial infarction. See MPEP § 2143(I)(G).
Consequently, Atsushi et al as modified by Kuzo et al and Rissanen et al render obvious a method of generating an animal model of myocardial infarction, wherein the shunt tube is implanted into the left anterior descending artery via the carotid artery. This therefore renders obvious the method of the instant claim.
Claims 9-10, 12, and 15-28 are rejected under 35 U.S.C. 103 as being unpatentable over Atsushi et al (JP2015057984A, translation provided by Global Dossier, of record) in view of Kuzo et al (JP2011097850A, translation provided by Global Dossier, of record), and further in view of Levine et al (Circulation, 2012, of record).
The discussion of Atsushi et al in view of Kuzo et al regarding claim 9 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Atsushi et al as modified by Kuzo et al render obvious claims 9-10, 12, 15-16, and 18-28. Levine et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 17: As aforementioned in the discussion of claim 9, Atsushi et al as modified by Kuzo et al teach a method of modeling myocardial infarction in a pig, wherein a polyvinyl chloride shunt tube is inserted into the left anterior descending coronary artery of the pig, such that the shunt tube is sized to fit the inner diameter of the artery – or has an outer diameter that is 100% of an inner diameter of the left anterior descending coronary artery – and has an inner diameter that is about 50% of the outer diameter of the tube.
The combination of Atsushi et al and Kuzo et al fail to teach that the porcine model comprising the implanted shunt tube is bred, as required by instant claim 17.
Levine et al, however, disclose that there is a risk of reinfarction or death in humans that have previously experienced a myocardial infarction and are sexually active (Page 1060, Sexual Activity and Myocardial Infarction).
Therefore, it would have been prima facie obvious to have modified the method of Atsushi et al in view of Kuzo et al such that the porcine models of myocardial infarction are bred to assess the risk of death, as taught in Levine et al. One of ordinary skill in the art before the filing date of the instant invention would have been motivated to evaluate all known risks that are associated with myocardial infarction in humans within the porcine models, and would have had a reasonable expectation of success since animal model breeding is a standard practice that is well-known in the art. See MPEP § 2143(I)(G).
Consequently, Atsushi et al as modified by Kuzo et al and Levine et al render obvious a method of generating an animal model of myocardial infarction, wherein the porcine model comprising the implanted shunt tube is bred. This therefore renders obvious the method of the instant claim.
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 ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633