DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Applicants’ response of 6/12/2026 has been received and entered into the application file. Claims 21, 22 and 24-27 are pending, all of which have been considered on the merits.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 21, 22 and 25 under 35 USC 102(b) as being anticipated by Hariri et al:
The amendment to claim 21 to require steps of a) contacting a first chorion tissue layer and at least one additional chorion tissue layer with at least one antibiotic, and then b) rinsing the chorion tissue layers to remove the at least one antibiotic is effective to obviate the rejection of record. As noted by Applicant, while Hariri et al teaches impregnating the grafts with a molecule, such as an antibiotic, Hariri et al does not teach then rinsing its grafts to remove the antibiotic. The rejection is withdrawn.
RE: Rejection of claims 21-25 under 35 USC 103(a) over Hariri et al:
As above, the amendment to claim 21 to require a) contacting… and b) rinsing… are effective to obviate the rejection of record. As noted by Applicant, while Hariri et al teach impregnating the graft with a molecule, such as an antibiotic, Hariri et al does not teach rinsing the molecules off, and rinsing off would be counterproductive, as the molecules are intended for delivery to the subject. The rejection is withdrawn.
RE: Rejection of claims 21-27 under 35 USC 103(a) over Hariri et al, in view of Schankereli et al:
For the reasons discussed above, the base rejection over Hariri et al is overcome, Schankereli et al does not cure the deficiencies. The rejection is withdrawn.
RE: Rejection of claims 21, 22, and 25 under 35 USC 103(a) over Klen, in view of Sulner et al:
The amendment to claim 21 to require a) contacting… and b) rinsing… are effective to obviate the rejection of record. Neither Klen nor Sulner et al disclose these steps. The rejection is withdrawn.
RE: Rejection of claims 21-25 under 35 USC 103(a) over Klen, in view of Sulner et al, and further in view of Tseng:
The amendment to claim 21 to require a) contacting… and b) rinsing… are effective to obviate the rejection of record. Tseng does not cure the deficiencies of Klen and Sulner et al, as Tseng does not teach rinsing the antibiotics off. The rejection is withdrawn.
RE: Rejection of claims 21, 22 and 25-27 under 35 USC 103(a) over Klen, in view of Sulner et al, and further in view of Schankereli et al:
For the reasons discussed above, the base rejection over Klen in view of Sulner et al is overcome, Schankereli et al does not cure the deficiencies. The rejection is withdrawn.
RE: Rejection of claims 21-27 on grounds of NSDP over one or more claims of each of US Patents 8357403, 9272003, 9533011, 9186382, 9433647, 9463207, 10874697, 9265800, 9272005 11504449, 8642092:
Applicants have filed terminal disclaimers over the above 11 patents. The terminal disclaimers have been approved and recorded. The rejections are withdrawn.
New Grounds of Rejection
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 negatived by the manner in which the invention was made.
Claims 21, 22, 24 and 25 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Hariri et al (US 2004/0048796), in view of Tyszkiewicz et al (Ann Transplantation, 1999).
Hariri et al disclose collagen biofabrics made from amniotic membranes (See Hariri et al, ¶0037). The collagen biofabrics are produced by: processing placental membranes to separate the amnion from the chorion (See Hariri, ¶0080); decellularizing the amniotic membrane to remove substantially all cells (See Hariri et al, ¶0083); washing the decellularized amniotic membrane (See Hariri et al, ¶0093); drying the decellularized amniotic membrane, wherein the drying involves placing the amniotic membrane, fetal side down, onto a drying frame (See Hariri et al, ¶0104), and heat drying the amniotic membrane under vacuum (See Hariri et al, ¶0107). The result is a dehydrated amniotic membrane (See Hariri et al, ¶0107). The dehydrated collagen biofabric can then be placed in a sterile container, such as a peel pouch, and be sealed (See Hariri et al, ¶0100).
Hariri et al teach that laminates can be created by performing the above described method, but layering at least two of the decellularized amniotic membranes on each other, and then drying them together, to thereby form the laminate (See Hariri et al, ¶0115).
Hariri et al also teach that chorionic membrane may be used in the same manner as amniotic membrane (See Hariri et al, ¶0055, 0112). Thus Hariri et al teach use of chorionic membranes to form multi-layered laminates of chorionic membranes.
Regarding claim 21: The method of making multi-layered laminates of chorionic membranes is relied upon for this rejection. The multi-layered laminates of chorionic membranes are dehydrated tissue grafts.
The step of placing a first decellularized chorionic membrane on the drying frame reads on c) placing a first chorion tissue layer on a drying frame.
The step of layering at least one additional decellularized chorionic membrane on top of the first decellularized chorionic membrane reads on d) adding at least one additional chorion tissue layer to the first chorion tissue layer.
The step of drying the decellularized chorion tissue layers under vacuum reads on e) dehydrating the chorions so as to produce a dehydrated tissue graft.
The step of placing the dehydrated multi-layered laminate of chorionic membranes into a peel pouch reads on f) placing the dehydrated tissue graft in a package.
The step of sealing the peel pouch reads on g) sealing the package.
Hariri et al differs from the instantly claimed method in that Hariri et al does not teach first a) contacting the individual chorion layers with at least one antibiotic, then b) rinsing the chorion tissue layers to remove the at least one antibiotic prior to c) placing the chorion tissue layers on the drying fixture and d) dehydrating, etc.
Hariri et al only provides brief comments on treatment of the placenta after harvest and prior to separation of the amniotic membrane from the chorionic membrane. Specifically, they describe taking the placenta immediately after cesarean section delivery, collecting under aseptic conditions, storing under refrigerated conditions, and performing serological and bacteriological tests (See Hariri et al, ¶0071-0078). As Hariri et al does not provide great detail on handling the placenta between point of harvest and separation of the individual membranes, Tyszkiewicz et al is referenced to supplement what was known at the time the application was filed. Like Hariri et al, Tyszkiewicz et al are also directed to processing placental membranes for use as tissue grafts. Tyszkiewicz et al teaches amniotic sacs are collected following birth, immediately placed in disposable jars containing 0.9% NaCl with penicillin G, gentamycin, and amphotericin B and stored at 4oC until transported to tissue bank facility. Upon receipt at the facility, the amniotic sacs are washed 3-5 times in cold 0.9% NaCl solution with magnetic stirrer to remove antibiotics, blood and mucus. After washing, the amniotic membrane and chorionic membranes were separated and further processed (See Tyszkiewicz et al, Pg 85-87 “Materials and Methods”). (While Tyszkiewicz et al goes on to process the amniotic membrane, they are relied upon for the details of the handling of the amniotic sac between harvest and separation of the amniotic membrane from the chorionic membrane.)
It is submitted it would have been prima facie obvious to one having ordinary skill in the art, to modify the method of Hariri et al to incorporate the specific processing steps outlined in Tyszkiewicz et al related to handling of the placental tissue (i.e. amniotic sac) between harvest and separation of the amniotic and chorionic membranes, specifically, the collection of the placentas into individual jars containing 0.9% NaCl and antibiotics, storing at 4o for transport to tissue bank, and then washing with 0.9% NaCl to remove the antibiotic, blood and mucus before further processing. This conclusion of obviousness is based on the fact that Tyszkiewicz et al teach these are appropriate steps for handling placental tissue (i.e. amniotic sac) intended for preparation and processing for tissue grafts. This falls within the ‘teaching, suggestion or motivation’ rationale. One would be motivated to adopt these specific steps in order to ensure sterility and suitability of the tissue for use as tissue grafts.
Upon incorporating the above described processing steps of Tyszkiewicz et al into the method of Hariri et al, the step of collecting multiple placentas/amniotic sacs into individual jars containing 0.9% NaCl with antibiotics reads on a) contacting a first chorion tissue layer and at least one additional chorion tissue layer with at least one antibiotic. It is noted that Hariri et al permits for provision of multiple amniotic and/or chorionic layers (See Hariri et al, ¶0059), thus they render obvious collection multiple placenta to obtain sufficient material for said layering.
The step of performing 3-5 washings with 0.9% NaCl to wash away the antibiotic, blood and mucus reads on the step of b) rinsing the chorion tissue layers to remove the at least one antibiotic.
As such, the method of claim 21 is considered obvious over Hariri et al in view of Tyszkiewicz et al.
Regarding claim 22: At ¶0059, in discussing production of multi-layered laminates, Hariri et al teach that at least 6, at least 8, at least 10… at least 1000 amniotic membranes can be layered upon one another. This teaching is extendable to the production of multi-layered chorionic membranes. This is considered to read on wherein at least two or more additional layers of chorion are added during step b).
Regarding claim 24: Following the discussion of claim 21 above, Tyszkiewicz et al teaches use of gentamicin [gentamycin], but does not specify gentamicin sulfate. However, official notice is taken that selection of gentamicin sulfate would have been prima facie obvious to one having ordinary skill in the art at the time the application was filed, as it was one of a finite number of commercially available salt formulations of the antibiotic with predictable properties.
Regarding claim 25: Following the discussion of claim 21 above, the peel pouch reads on a pouch.
Claims 21, 22, and 24-27 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Hariri et al (US 2004/0048796), in view of Tyszkiewicz et al (Ann Transplantation, 1999), and further in view of Schankereli (US Patent 5782914).
The teachings of Hariri et al and Tyszkiewicz et al are set forth above. Hariri et al, in view of Tyszkiewicz et al, renders obvious claims 21, 22, 24 and 25. Regarding claims 26-27: The sealed pouch of Hariri et al differs from the instant claims in that Hariri et al is silent as to whether the peel pouch contains an inner pouch, and wherein, following sealing the inner pouch, the sealed pouch is placed in an outer pouch, which is subsequently sealed.
Schankereli is cited for disclosure of moisture-proof sterilizing pouches which actually contain an inner and outer pouch, said inner pouch being nested within the outer pouch. The nested format facilitates sterile handling in an operating room (See Schankereli, col. 4, ln 33-41). Schankereli’s pouches are specifically designed for use with dehydrated transplantable tissue . The pouches are evacuated of oxygen (replaced with argon or nitrogen) to limit free radical formation (oxidation) of the tissue during sterilization process, thus inhibiting chemical and physical changes to the tissue (See Schankereli, col. 3, ln 57-col. 4, ln 22).
Given that both Hariri et al and Schankereli teach sealed containers for storage of dehydrated tissue grafts at room temperature, it would have been prima facie obvious to have substituted the double pouch of Schankereli for the peel pouch of Klen. Substitution of one element for another known in the field is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395. The double pouch of Schankereli reads on wherein the package is a pouch, wherein the pouch is an inner pouch, and then following sealing the dehydrated tissue in the inner pouch, the sealed pouch is placed in an outer pouch, which is subsequently sealed.
Claims 21, 22, 24 and 25 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Klen (International Congress on Research in Burns, 1970), in view of Sulner et al (US 2007/0038298), and further in view of Tyszkiewicz et al (Ann Transplantation, 1999).
Klen teach preparation of placental tissue grafts for use on burns. Klen disclose a protocol comprising: obtaining a full placenta, placing the placenta with the side from which the umbilical cord protrudes face down in a basin, cutting radially from the edge of the placenta to cut out the umbilical cord stump (See Klen Pg. 289). The recovered material is understood to be a flat sheet of full thickness placenta (containing amnion, spongy layer/connective tissue layer, and chorion). Klen teach submerging the membranes into saline to wash away the majority of blood-clots, stretching the membranes onto strips of plastic net, covering the grafts by Tylexol, rolling up the grafts, inserting the rolled up grafts into vessels, plugging the vessels, filling the vessels with nitrogen, performing a primary freeze-drying (sublimation) step at -25o C, performing a secondary drying step by drying at a temperature of 39o C under vacuum, replacing vacuum with nitrogen, and sealing the bottles. The samples are storable at room temperature (See Klen, Pg. 290).
Klen also reference amnion, chorion and combined amnion-chorion grafts (See Klen, Pg. 289). Thus while the exemplified method of Klen is carried out on a full thickness placenta, Klen is also considered to disclose separation of amnion from chorion and separately processing each of these membranes in the same manner, individually. The embodiment of processing the individually, isolated chorion membrane of Klen is relied upon for the instant rejection:
Regarding claim 21: The method of Klen produces a dehydrated tissue graft. Applying the same processing methods to the chorion which has been separated from the amnion would yield a dehydrated chorion-only membrane. The method steps rendered obvious by Klen are comparable to the instant claims as follows:
The step of placing the chorion-only membrane on the strip of plastic net reads on d) placing a first chorion tissue layer on a drying fixture.
The step of subjecting the chorion-only membrane to the freeze-drying then drying under vacuum read on e) dehydrating the chorion[s] so as to produce a dehydrated tissue graft.
The steps of rolling up the grafts, and inserting the rolled up grafts into vessels reads on f) placing the dehydrated tissue graft in a package (the vessel reading on a package).
The step of plugging the vessels reads on g) sealing the package.
Klen differs from the method of the instant claims they do not d) add at least one additional chorion tissue layer onto the first chorion tissue layer.
Klen further differ from the instantly claimed method in that they do not teach first a) contacting the individual chorion layers with at least one antibiotic, then b) rinsing the chorion tissue layers to remove the at least one antibiotic prior to c) placing the chorion tissue layers on the drying fixture and d) dehydrating, etc.
Regarding the first difference d) provision of multiple chorion layers: Sulner et al, who is also directed to processing of placental membranes for formation of tissue grafting materials, teaches that multiple placental membrane (i.e. amnion and/or chorion) may be laminated together, and that lamination may provide greater stiffness and durability during the healing process (See Sulner et al, ¶0033).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art, at the time the invention was made to have layered multiple chorion-only grafts together, each chorion obtained from separate placenta, on the plastic nets, covered the combination with Tylexol, and then dried the combination, thereby resulting in a dehydrated, multi-layered tissue graft comprising at least two layers of chorion tissue. The step of layering additional chorion-only membranes onto the first chorion membrane reads on d) adding at least one additional chorion tissue layer to the first chorion tissue layer. The motivation to do so is found in Sulner et al, who teaches that lamination provides greater stiffness and durability. One would have had a reasonable expectation of doing so because Klen teach how to produce chorion-only membranes, and layering multiple tissue layers over one another is well within the purview of the artisan of ordinary skill.
Regarding the second difference, the steps of a) contacting the chorion layers first with an antibiotic, and then b) rinsing: Klen only provides brief comments on treatment of the placenta after harvest and prior to separation of the amniotic membrane from the chorionic membrane. Specifically, they describe collecting the placenta following delivery in sterile operating basins, keeping cool if not used immediately, cutting the umbilical cord, and then submerging the placental membrane material into saline to wash away majority of blood clots (See Klen, Pg 289). As Klen does not provide great detail on handling the placenta between point of harvest and processing of the individual membranes, Tyszkiewicz et al is referenced to supplement what was known at the time the application was filed. Like Klen, Tyszkiewicz et al are also directed to processing placental membranes for use as tissue grafts. The teachings of Tyszkiewicz et al are set forth above.
It is submitted it would have been prima facie obvious to one having ordinary skill in the art, to modify the method of Klen to incorporate the specific processing steps outlined in Tyszkiewicz et al related to handling of the placental tissue (i.e. amniotic sac) between harvest and separation of the amniotic and chorionic membranes, specifically, the collection of the placentas into individual jars containing 0.9% NaCl and antibiotics, storing at 4o prior to processing, and then washing with 0.9% NaCl to remove the antibiotic, blood and mucus before further processing. This conclusion of obviousness is based on the fact that Tyszkiewicz et al teach these are appropriate steps for handling placental tissue (i.e. amniotic sac) intended for preparation and processing for tissue grafts. This falls within the ‘teaching, suggestion or motivation’ rationale. One would be motivated to adopt these specific steps in order to ensure sterility and suitability of the tissue for use as tissue grafts.
Upon incorporating the above described processing steps of Tyszkiewicz et al into the method of Klen, the step of collecting multiple placentas/amniotic sacs into individual jars containing 0.9% NaCl with antibiotics reads on a) contacting a first chorion tissue layer and at least one additional chorion tissue layer with at least one antibiotic. For the reasons discussed above, Klen renders obvious collection of multiple chorion from multiple placenta.
The step of performing 3-5 washings with 0.9% NaCl to wash away the antibiotic, blood and mucus reads on the step of b) rinsing the chorion tissue layers to remove the at least one antibiotic.
Regarding claim 22: Following the discussion of claim 21 above, in situations where at least three chorion membranes are provided together, provision of a third chorion tissue will read on b) adding at least two or more additional layers of chorion.
Regarding claim 24: Following the discussion of claim 21 above, Tyszkiewicz et al teaches use of gentamicin [gentamycin], but does not specify gentamicin sulfate. However, official notice is taken that selection of gentamicin sulfate would have been prima facie obvious to one having ordinary skill in the art at the time the application was filed, as it was one of a finite number of commercially available salt formulations of the antibiotic with predictable properties.
Regarding claim 25: Following the discussion of claim 21 above, the vessel can be considered to read on a pouch. The dictionary definition of “pouch” is “a bag of small or moderate size for storing or transporting goods” (See Merriam-Webster online dictionary “pouch”, IDS Ref #246). The broadest reasonable interpretation of this term will thus encompass any small or moderate size container (term “bag” is broadly interpreted as a container), it is not limited in terms of flexibility/rigidity or other structural features.
Claims 21, 22, 24, 25-27 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Klen (International Congress on Research in Burns, 1970), in view of Sulner et al (US 2007/0038298), further in view of Tyszkiewicz et al (Ann Transplantation, 1999), and further in view of Schankereli (US Patent 5782914).
The teachings of Klen, Sulner et al and Tyszkiewicz et al are sets forth above. Klen, in view of Sulner et al, and further in view of Tyszkiewicz et al renders obvious claims 21, 22, 24 and 25.
Regarding claims 26-27: Klen teach storing the dehydrated placental tissue in vessels (bottles). Under the broadest reasonable interpretation of the claim, the bottle can read on ‘an inner pouch’. However, substitution of alternative packaging known in the art to be suitable for containing tissue grafts would have been prima facie obvious.
Schankereli is cited for disclosure of moisture-proof sterilizing pouches which actually contain an inner and outer pouch, said inner pouch being nested within the outer pouch. The nested format facilitates sterile handling in an operating room (See Schankereli, col. 4, ln 33-41). Schankereli’s pouches are specifically designed for use with dehydrated transplantable tissue . The pouches are evacuated of oxygen (replaced with argon or nitrogen) to limit free radical formation (oxidation) of the tissue during sterilization process, thus inhibiting chemical and physical changes to the tissue (See Schankereli, col. 3, ln 57-col. 4, ln 22).
Given that both Klen and Schankereli teach deoxygenated containers for storage of dehydrated tissue grafts at room temperature, it would have been prima facie obvious to have substituted the double pouch of Schankereli for the bottles of Klen. Substitution of one element for another known in the field is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395. The double pouch of Schankereli reads on wherein the package is a pouch, wherein the pouch is an inner pouch, and then following sealing the dehydrated tissue in the inner pouch, the sealed pouch is placed in an outer pouch, which is subsequently sealed.
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.
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/ALLISON M FOX/Primary Examiner, Art Unit 1633
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