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
Pursuant to the amendment dated 08/27/2025, claims 7, 9, 10, and 14 have been cancelled.
Claims 1-6, 8, 11-13, and 15-24 are pending and under current examination.
All rejections not reiterated have been withdrawn.
The provisional nonstatutory double patenting over US Application No. 17941487 has been withdrawn in view of the abandonment of that application.
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.
Claims 1-5, 12, 13, 17-20, 22 are rejected under 35 U.S.C. 103 as being unpatentable over Ji et al. (US 2009/0062233; publication date: 05/05/2009; cited in the IDS filed 01/27/2023) in view of Figuly et al. (US2010/0112063; publication date: 05/06/2010).
With regard to claims 1-5, Ji discloses a method of promoting tissue healing after surgery (0072 and 0073) by administering to the surgical site a composition comprising a modified starch (abstract). The starch of the invention comprises at least one epichlorohydrin crosslinked starch and one crosslinked carboxymethyl starch (0140). The composition contains epichlorohydrin crosslinked starch, water (0185), and the sodium salt of carboxymethylated starch (i.e. a salt 0051). The composition may be applied as a powder or a gel (0176). The modified starch may have a molecular weight between 15,000 to 2,000,000 Daltons (0083). This range overlaps with the range recited in the instant claims. The starch may have a particle size of from 30 -500 microns (0083). This range embraces the range recited in the instant claims. See MPEP 2144.05.
Ji does not disclose that the surgical site is an anastomotic site.
Figuly discloses that hydrogels are useful for replacing or supplementing staples or staples in internal surgical procedures such as intestinal anastomosis and vascular anastomosis (0024).
It would have been prima facie obvious to apply the starch material disclosed by Ji to an anastomotic site because one having ordinary skill in the art would have recognized “anastomotic site” as a species falling within the genus of “surgical site” disclosed by Ji. See MPEP 2144.08. In the instant case, one having ordinary skill in the art, e.g. an individual with a Ph.D. in biomedical research or a M.D., would recognize that the ability of Ji’s invention to prevent wounded tissue or organs from adhering to tissue or organs in the vicinity [of a wound site] and reduce local bleeding by mechanically isolating the wound or wound surface from adjacent tissue and surrounding organs (0072) as well as its ability to promote healing, form a seal, and act as a protective coating etc. in wounds resulting from surgery (0073, 0114) would have been beneficial in the specific procedure of forming an anastomosis.
With regard to the limitation of instant claim 1 requiring the carboxymethylated starch to be 25-45% crosslinked, Ji discloses that by using bifunctional or polyfunctional chemical agents to cross-link the raw starch macromolecules, the starch acquires enhanced hydrophilic properties and viscosity/adhesiveness in a water solution (0127). Thus, crosslinking was a recognized method to control viscosity and adhesiveness of the hydrogel material. It would have been merely routine for one of ordinary skill to optimize viscosity/adhesiveness by adjusting the crosslinking of the modified starch in Ji’s invention.
With regard to claim 12, the modified starch is the sodium salt of carboxymethylated starch (0051).
With regard to claim 13, Ji discloses that inter alia selecting proportional ratios of amylopectin and amylose is a factor that can alter the hydrophilic property and viscosity of the modified starch, which produces an adhesive gel (0176). It would have been prima facie obvious to optimize the relative proportions of amylose and amylopectin in the starch in order to optimize viscosity for any given application. See MPEP 2144.05.
With regard to claims 17-19, Ji discloses applying the modified starch as either a powder or a gel. Claims 16-18 specify the order of steps in which a gel is formed; however, any order of steps is considered prima facie obvious, absent evidence of their criticality for an unexpected property or outcome of the claimed invention. See MPEP 2144.04(IV)(C).
With regard to claims 20 and 22, as noted above, the hydrogel is formed with water (see e.g. 0185).
Claims 6, 8, 11, 15, 16, 21, 23, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Ji et al. (US 2009/0062233; publication date: 05/05/2009; cited in the IDS filed 01/27/2023) in view of Figuly et al. US2010/0112063; publication date: 05/06/2010) as applied to claims 1-5, 7, 9, 10, 12-14, 17-20, and 22 and further in view of Fukuda (WO2014/192807; publication date: 12/04/2014; citing the US National Stage, US20160095962, as an English translation) as evidenced by Hospira (Lactated Ringer’s Solution Spec Sheet; last revised May 2009).
The relevant disclosures of Ji and Figuly are set forth above. Neither discloses adding a salt, the specific salts recited in the instant claims, the pH, or the variations of Ringer’s solution recited in instant claims 6, 8, 11, 15, 16, 21, 23, and 24.
Fukuda, in the analogous art of antiadhesive surgical gels, discloses that hydrogels can be hydrated with saline or lactated Ringer’s solution (0129).
It would have been prima facie obvious to use saline or lactated Ringer’s solution to hydrate the gel-forming modified starch in Ji’s method. The artisan of ordinary skill would have been motivated to do so in order to provide a gel having physiological pH and/or salt concentrations to improve compatibility with the surgical site. The skilled artisan would have had a reasonable expectation of success because Fukuda indicates these solutions to be suitable for this purpose.
Establishing the obviousness of adding saline or lactated Ringer’s solutions to the modified starches disclosed by Ji addresses the limitations of instant claims 6, 8, 11, 21, 23, and 24. The examiner notes that, although claim 7 is considered obvious as set forth above over Ji and Figuly, this reasoning is also applicable to the limitations of instant claim 7.
With regard to claims 15 and 16, Hospira discloses that lactated Ringer’s solution contains 600 mg NaCl, and 30 mg potassium chloride per liter (i.e. total concentration 0.063g/100mL sodium chloride + potassium chloride) and has a pH of between 6-7 (page 1). Thus, a hydrogel that has been formed using lactated Ringer’s solution would possess salt within the range required by instant claim 15 and have pH in the range required by instant claim 16.
Response to Arguments
Applicant's arguments filed 08/27/2025 have been fully considered but they are not persuasive.
On page 5, Applicant argues that the examiner has not identified any teachings in Ji that would have led one of ordinary skill to Figuly. Applicant argues that Ji discloses treating wound surfaces to prevent bleeding and fluid exudation and that this is not anastomosis, a surgical connection performed to restore continuity after resection or injury or to reestablish specific functionality of a conduit structure. Applicant points out that Ji does not address this application. On pages 5-6, Applicant describes some of the events underlying wound healing. On page 6, Applicant argues that the indications of Ji and the instant invention differ and that the instant invention relates to wound healing and rapid, uncomplicated tissue integration. On page 6, Applicant argues the instant specification makes clear that wound healing is not facilitated merely by physically favorable properties as in Ji but rather by inducing an immunologically relevant effect that occurs after hemostasis and subsequent healing phases, citing page 14 of the specification. Applicant argues that these immunological effects are directly related to molecular weight of a specific range, particle size of a specific range an specific degree of crosslinking, citing page 8 of the specification.
In response, the examiner disagrees with Applicant’s conclusion. As explained in the rejection above, one having ordinary skill would have recognized anastomoses as falling within the category of surgical wound and Ji expressly suggests internal application (0070). Many benefits to surgical wounds are described by Ji including promoting tissue healing, acting as a scaffold, sealing and preventing drainage, and preventing adhesion in undesirable areas (0072 and 0073). Additionally, Ji recognized the following: “the interaction between the formed blood coagulation matrix and the functional groups of tissue proteins causes the “starch-blood coagulation matrix” to adhere to and seal the wounded tissue, resulting in hemostasis.” Thus, many of the physiological benefits of the claimed composition appear to have been recognized as of the instant effective filing date. Moreover, the benefits of the particular starches recited in the instant claims are properties of the starches that have already been disclosed for application to internal surgical wounds. In response to applicant's argument that show benefit for anastomoses in terms of extent of water absorption or immunologically relevant events, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). With regard to the argument that the indications of Ji and the instant invention differ, the examiner respectfully disagrees. The claimed method is a subcategory of the method described by Ji that one having ordinary skill would have been aware of. With regard to the argument that the immunological effects of the instant invention are directly related to molecular weight of a specific range, particle size of a specific range an specific degree of crosslinking, please see further discussion of the burden on Applicant to overcome an obviousness rejection with a persuasive showing of unexpected results below. Briefly, no criticality of the claimed ranges to any unexpected property in a side by side comparison to the closest prior art has been made of record.
On page 6, Applicant argues that Ji provides no guidance or preferred ranges [in ratio of amylose to amylopectin] for optimization of viscosity. Applicant argues further on page 6 that other parameters such as molecular weight and crosslinking also influence viscosity of starch and that due to these complex interactions it is not readily predictable which ratio will produce the desired properties in a particular case. Applicant argues that the optimal viscosity is always application-specific such that a ratio suitable for one purpose may prove unsuitable in another context. On page 7 Applicant argues further that in contrast, the present invention uses certain other parameters to control gel formation and viscosity of the modified starch, the molecular weight, particle diameter, and degree of crosslinking. Applicant points out that this is accompanied by unique properties of the specified carboxymethylated starch such as reduced water absorption, which in turn provides the benefit of reduced necrosis.
The examiner maintains the opinion that optimizing viscosity would have been merely routine for one having ordinary skill, i.e. an individual with a Ph.D. in biomedical formulations science, even though more than one factor contributes to this property. Indeed Ji also recognized that viscosity can be influenced by various factors including degree of crosslinking and origin of the starch (0043). The examiner acknowledges that optimal viscosity would vary among applications; however, it would have merely required testing several different products adjusting art-recognized variables to achieve a desirable application (see MPEP2144.05). The examiner respectfully disagrees with the position that optimizing viscosity of the hydrogel would have been too complex for one having ordinary skill in this art.
On page 7, Applicant points out example 2 of the instant specification as demonstrating that water absorption of the pharmaceutical composition comprising carboxymethylated starch according to the present invention is much lower than that of other commercially available products therefore risk of necrosis is reduced in anastomoses treated with a gel comprising carboxymethylated starch with the features of amended claim 1. On page 7, Applicant describes an experiment from the instant specification showing changes in collagen expression and hydroxyproline content and arguing that these increases are an indicator of improved anastomosis healing effect of the claimed invention.
Insomuch as this may be an assertion of unexpected results, please refer to MPEP 716.02(b) which details the burden on Applicant to establish that results in a side-by-side comparison to the closest prior art are unexpected and significant. Specifically, Applicant must establish that differences in results are in fact unexpected and unobvious and are of both practical and statistical significance. Additionally, evidence of unexpected properties must be commensurate in scope with the claims.
In the instant case, experiment 1 of the instant application compares anastomosis treatment with an example according to the instant method to treatment with a saline solution control treatment and experiment 2 compares water absorption to other known absorbent wound dressings; however, none of these comparators reflect the closest prior art. One would have expected an improvement in healing over saline treatment, and the absorptive capacity of epichlorohydrin modified starch and carboxymethylated starch were optimizable properties as of the instant effective filing date. Additionally, the data do not establish criticality of any claimed range with regard to an unexpectedly superior property of the instant invention. In summary, the burden to overcome an obviousness rejection has not been met because no unexpected performance over the closest prior art has been established on the record.
On page 8, Applicant argues that Figuly is not combinable with Ji. Applicant argues that the term hydrogel is a generic umbrella term that does not provide any information regarding the type of hydrogel and the specific field of application, its effect of effectiveness. Applicant argues that hydrogels used for contact lenses or diapers would not be suitable for wound healing.
This argument is not found persuasive because both Ji and Figuly are in the analogous art of wound healing, and because Ji describes very similar surgical wounds to anastomoses and finally because one having ordinary skill would recognize that the recognized benefits would also extend to anastomosis treatment. The artisan of ordinary skill would also have realized that hydrogels for contact lenses or diapers would not be particularly suited to wounds, whereas the hydrogel disclosed by Ji was well-suited for treating internal surgical wounds (as detailed above).
On page 8, Applicant argues that Figuly describes a different hydrogel than that claimed in the instant method.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
On pages 8-9, Applicant argues that the examiner has used impermissible hindsight reconstruction.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE PEEBLES/Primary Examiner, Art Unit 1617