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 .
Response to Applicants Amendments/Arguments
The claim objection is removed because hyaluronic acid has been added to the abbreviation “HA” in the claims. Claims 55-56 have been canceled so the 112(b) and art rejections are withdrawn. Because of the most recent amendments made to the claims of Application 17/778,333, the double patenting rejection is withdrawn. Claims 39-43,45,49-54 are under examination.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 39-40,42-43,45,49-54 are rejected under 35 U.S.C. 103 as being unpatentable over Tseng (US 20150342998) in view of Tseng II (US 20140147511)
and Daniel (US 20140017280). Daniel is already of record and has been used in previous office actions.
Tseng teaches a therapeutic composition that comprises morselized amniotic membrane tissue and morselized umbilical cord tissue (Abstract). Paragraph 27 of Tseng further states that the mixture of morselized amniotic membrane tissue and umbilical cord can be in any ratio from 0.001:99.999 w/w% to 99.999:0.001 w/w % and can be morselized from either fresh or frozen tissue. The morselized tissue pieces can range in size from about 0.1 mm to about 1.0 cm in length, width, or thickness which would be consistent with a particle size (Paragraph 27 of Tseng). Tseng teaches that the proportion of UCAM (umbilical cord) and amnion described herein in the composition can vary from between 0.01% to about 99.9 wt.% of the total amount of the composition (Paragraph 54 of Tseng). Thus, Tseng suggests that the amount of morselized amnion can be roughly 0.001 to 99.999% of the entire composition and the amount of morselized umbilical cord can similarly be in the range of roughly 0.001 to 99.999% of the entire composition. The umbilical cord used in Tseng can include all the umbilical cord components (Paragraphs 3-4 of Tseng). Tseng teaches that the resulting morsels can be further homogenized (Paragraph 27 of Tseng) and lyophilized/dehydrated (Paragraphs 6 and 31-33 of Tseng) as in instant 39.
Tseng teaches that its composition can be used as a treatment (Paragraphs 6 and 12 of Tseng). In paragraph 84, Tseng mentions that the composition can be used to treat conditions such as rheumatoid arthritis which is considered a musculoskeletal disorder that causes damages to joints, bones, and the surrounding tissue. Tseng does not teach administering the composition to the knees specifically. However, Tseng II teaches that such a placental tissue particulate composed of whole umbilical cord, amnion, and chorion (Paragraphs 3, 33, and 46 of Tseng II) can be used to treat a host of conditions including osteoarthritis, rheumatoid arthritis, septic arthritis, ankylosing spondylitis by injecting the placental tissue particulate directly into a joint such as a knee (Paragraph 245 of Tseng II). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have administered the treatment into an impacted knee as taught by Tseng II. An artisan would have been motivated to have treated a knee specifically because Tseng II discloses that a “placental/fetal support tissue power product disclosed herein is used to treat arthritis (e.g. osteoarthritis, rheumatoid arthritis, septic arthritis, ankylosing spondylitis, spondylosis). In some embodiments, a fetal support tissue powder product disclosed herein is injected into an arthritis joint (e.g. a knee) (Paragraph 245 of Tseng II). Because paragraph 254 of Tseng II discloses that injection into a joint such as a knee can cure different types of arthritis, there would have been a high expectation for success as in instant Claim 39.
Paragraph 38 and Claim 14 of Tseng state that “at least some chorion tissue remains with the morselized amniotic membrane tissue.” Tseng is silent on the amount of chorion that can be included. However, Daniel teaches a placental therapeutic composition in which the amount of chorion is in the range of 20 to 60% (Paragraph 59 of Daniel). Daniel further teaches that the amount of amnion present can be 10 to 50% (Paragraph 59 of Daniel). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have used the amount of chorion/amnion taught by Daniel. An artisan would have been motivated to have used that amount of chorion and amnion taught by Daniel because it can treat joints/bone (Paragraph 31 of Daniel). There would have been a high expectation for success because paragraph 31 of Daniel teaches that the composition with a percent weight of chorion of 20 to 60% can successfully treat a range of disorders and conditions associated with bones and joints (Paragraph 31 of Daniel) as in instant Claims 39,51.
The claim recites that the amount of particulate composition is at least 200 mg. The amount of particulate material used will be dependent upon the area of the joint that needs to be treated. MPEP § 2144.05 (II) states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In reHoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc.v.Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In reKulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int' l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
A review of the specification fails to provide evidence that the claimed concentration of the particulate composition is critical. Absent such evidence it would have been obvious to an artisan of ordinary skill at the time of effectively filing Tseng to try a finite number of possible concentrations of placental tissue particulate to predictably arrive at the claimed concentration through routine optimization. The amount needed would depend upon the size of the wound and/or damaged site. An artisan would have had a reasonable expectation of success in optimizing the concentrations because determining the amount of placental particulate was long established in the art as demonstrated by Tseng. Thus, the reference renders the instantly claimed concentration of at least 200 mg.
Since the 3 references cited teach the claim limitations, it would be expected that the placental particulate composition taught by the combination of the references would reduce pain as measured by a patient outcome score, causing more than an eight point difference in mean change from the baseline WOMAC pain score and delay the progression of tissue damage which can be measured by an X-ray and/or MRI as in instant Claims 39,42.
Dependent Claims taught by Tseng
Tseng teaches wherein the method comprises injecting a single localized injection of the therapeutically effective amount of the particulate composition (Claim 9 of Tseng) as in instant Claim 40. Tseng teaches wherein a second dose is administered within about two weeks (Paragraph 73 of Tseng) as in instant Claim 43. Tseng does not state that portions of the umbilical cord must be removed before being morselized; therefore, the umbilical cord can be morselized intact including all layers (Paragraphs 2-5 of Tseng) as in instant Claims 39,49-50. Tseng teaches wherein the particulate composition is dehydrated/lyophilized (Paragraphs 6 and 27 of Tseng) and filled with collagen (Paragraph 18 of Tseng) as in instant Claim 52. Tseng teaches wherein the particulate composition further comprises an antimicrobial agent or an antifungal agent (Paragraph 31 of Tseng) as in instant Claim 53.
Dependent Claims taught by Tseng II
Tseng II teaches that the material can consist of the whole umbilical cord (Paragraph 33 of Tseng II) as in instant Claims 39,49-50. Tseng II teaches that the placental composition can include collagen, hyaluronic acid, or fibrin (Paragraph 18 of Tseng II) and be dehydrated (Paragraph 39 of Tseng II) as in instant Claim 52. Tseng II teaches that the musculoskeletal disease can be osteoarthritis, rotator cuff repairs, or a cartilage deficit (Paragraphs 21-22,64-65, 201, or 203 of Tseng II) as in instant Calm 54.
Dependent Claims taught by Daniel
Daniel teaches injecting a single therapeutically effective amount of the particulate composition (Paragraph 76 of Daniel) as in instant Claim 40.
Since the references teach the placental product of claimed composition, it would be expected that the placental product produced by combining the teachings of the references cited would also be capable of reducing pain by more than an eight point difference form a baseline WOMAC pain score as in instant Claim 42. Furthermore, Tseng II mentions that such a particulate placental product also has growth factors (Paragraph 229 of Tseng II). Since the combined teachings of the references cited in the rejection also teach particulate placental material composed of amnion, chorion, and umbilical cord as recited in the claims, it would be expected that the particulate placental material taught in Tseng I, Tseng II, and Daniel would also be capable of producing quantifiable amounts of beta FGF, IL-1Rα,IL-1α, TIMP-1,TIMP-2,TIMP-3, and fibronectin as in instant Claim 45.
Tseng teaches a therapeutic composition containing amnion, chorion, and umbilical cord particulate material that can be used to treat musculoskeletal disorders such as rheumatoid arthritis. Tseng does not teach administering the placental particulate composition to a knee; however, Tseng II teaches that injecting such as composition into the knee is possible in order to treat conditions such as rheumatoid arthritis and/or osteoarthritis. An artisan would have been motivated to have administered such a treatment to the knee since that is a region that is commonly impacted by musculoskeletal disorders such as arthritis. Although Tseng and Tseng II mention that chorion material may be present in such a particulate composition, these references fail to state the precise amount of chorion material that may be present. However, Daniel teaches a placental particulate composition which is used to target bone/joint conditions. Daniel teaches an amount of chorion in its particulate composition within the range recited in the claims. An artisan would have been motivated to have used such an amount of chorion in a placental composition because Daniel teaches a placental composition with that concentration of chorion material used to treat bone/joints. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants invention, it must be considered, absent evidence to the contrary that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combinations would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. V. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature. These people will have the practical knowledge in molecular biology and placental product preparation. Therefore, the level of ordinary skill in the art is high.
Response to Applicants’ Arguments
Applicants argue that the combination of the three references, Tseng, Tseng II, and Daniel in this art rejection is not feasible because they each teach distinct particulate material and fail to teach a particulate composition “comprising a mixture of placental tissue particles (PTP), said PTP comprising about 10 wt% to about 30 wt% AM (amniotic membrane) particulate, about 30 wt% to about 75 wt% CM (chorionic membrane) particulate, and about 5 wt% to about 75 wt% UC (umbilical cord) particulate. All of these placental particulate materials can be used for support purposes in the body. The amnionic membrane particulate, chorion membrane particulate, and umbilical cord particulate all can have the same function which is providing support to injured/damaged areas. Therefore, it would be obvious to vary the amounts of each especially in such variations as taught in prior art references because they all serve the same purpose.
Applicants argue that Tseng “teaches a mixture of amniotic membrane and umbilical cord tissue in any ratio from 0.001:99.999 w/w% to 99.999:0.001 w/w % that can be morselized from either fresh or frozen tissue…..Tseng does not teach any composition that includes AM, UC, and CM together as distinct required components. While Tseng teaches that the amount of AM and UC can vary between 0.001% to 99.00% of the administered composition, the reference is fundamentally directed to AM and UC compositions, [not compositions with chorionic membrane]”
The examiner would have found this argument more persuasive if the specific amounts of amnion and chorion particulates recited in the instant claims did not have broad ranges. Tseng still teaches that the total amount of AM and UC particles in the therapeutic composition can vary between 0.001% to 99.00%. This means that other components can still be included and there is motivation for including other placental portions (like chorionic membrane particulates) that are also capable of providing support for muscle/skeletal conditions and/or injuries. Furthermore, paragraph 38 of Tseng states that chorion membrane can be included in the particulate composition. Paragraph 38 of Tseng even states, “in some embodiments, at least some chorion tissue remains with the morselized amniotic membrane tissue and the morselized umbilical cord tissue.” Therefore, Tseng allows for morselized chorion membrane to be present. Although many of Tseng’s embodiments are directed to compositions that contain amniotic membrane and umbilical cord, paragraph 38 does provide a valid teaching that chorionic membrane can also be included in the particulate composition. Therefore, Tseng is still a valid teaching and does indeed teach chorionic membrane material inclusion in its particulate composition.
Daniel is relied upon for teaching the percent composition of chorionic membrane in the particulate composition. Applicants argue, “Daniel is directed to a composition that comprises AM (amniotic membrane), CM (chorionic membrane), and Wharton’s jelly—not umbilical cord tissue as recited in claim 39. Wharton’s jelly is a distinct connective tissue component of the umbilical cord and is not equivalent to UC tissue as a whole.”
The examiner did not find this argument to be persuasive since Wharton’s jelly makes up roughly 60-65% of the umbilical cord and Wharton’s jelly is umbilical cord material. The instant set of claims just require umbilical cord particulate material and do not recite what specific type of umbilical cord material must be present in the composition.
Applicants further discuss the Declaration dated (June 23, 2026). Alessandra Pavesio argues that increasing the amounts of the claimed composition can result in unwanted side effects and she discusses the placental particulate composition with the best outcome (Sample PTP-001). Ms. Pavesio argues that superior results were seen in single injection of 50 mg/ml of sample PTP-001 (which contains amnion, chorion, and umbilical cord particulate material). PTP-001 has a specific amount of chorion particulate, amnion particulate, and umbilical cord particulate material present. It is not clear in the declaration what the specific amounts of chorion membrane particulate, amnion membrane particulate, and umbilical cord particulate are for PTP-001. Since PTP-001 would have specific amounts of chorionic membrane, amnion membrane, and umbilical cord membrane present, PTP-001 would represent one point within the broader range currently claimed which includes ranges for amniotic membrane particulate (about 10-30 wt%), chorion membrane particulate (about 30-75 wt%), and umbilical cord particulate (about 5-50 wt%). What is currently being claimed is much broader than the amount present in sample PTP-001 alone. Furthermore, the instant claims do not limit administration to a single injection at a dose of 50 mg/ml.
Claim 40-43,45,49-54 are rejected under 35 U.S.C. 103 as being unpatentable over Tseng (US 20150342998) in view of Tseng II (US 20140147511), Daniel (US 20140017280), and Brahm (US 20150088062). Brahm is already of record and has been discussed in previous office actions.
Tseng, Tseng II, and Daniel apply as above to teach claims 40,42-43,45,49-54 . These references fail to teach monitoring the placental composition implant and detecting (60 days plus after administration) the implant in order to ensure that the implant material is effectively treating the patient and not causing unwanted complications. Brahm teaches that after implantation of therapeutic material in a joint, the patient receiving the implant attends monthly follow up visits to check for healing (detection at the site) and/or monitoring complications that could develop (Paragraph 134 of Brahm). Paragraph 134 of Brahm specifically discusses monthly visits 4 weeks post-surgery and 11-weeks post-surgery (Paragraph 134 of Brahm). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have implemented the monitoring/detection taught by Brahm. An artisan would have been motivated to have implemented such monitoring/detection in order to ensure that the placental implant material was effectively healing in the wound area and that the patient was experiencing no pain after introduction of the implant material (Paragraph 134 of Brahm). Because monitoring and detection can be effectively used to assess the success of implanted material, there would have been a high expectation for success (Paragraph 134 of Brahm) as in instant Claim 41.
Tseng teaches a therapeutic placental composition containing amnion, chorion, and umbilical cord particulate material that can be used to treat musculoskeletal disorders such as rheumatoid arthritis. Tseng does not teach administering placental particulate composition to a knee joint; however, Tseng II teaches that injecting such a composition into the knee is possible in order to treat conditions such as rheumatoid arthritis and/or osteoarthritis. An artisan would have been motivated to have administered such a treatment to the knee joint since that is a region that is commonly impacted by musculoskeletal disorders such as arthritis. Although Tseng and Tseng II mention that chorion material may be present in such a placental particulate composition, these references fail to state the precise amount of chorion material that may be present. However, Daniel teaches a placental particulate material which is used to treat bones/joints. Daniel teaches an amount of chorion in its particulate composition recited within the range. An artisan would have been motivated to have used such an amount of chorion because Daniel teaches that such a composition can treat bone/joints. Furthermore, an artisan would have been motivated to have used the post implant monitoring taught in Brahm in order to ensure that the implant material was successfully adjusting to the wound and/or damaged site. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants invention, it must be considered, absent evidence to the contrary that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combinations would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. V. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature. These people will have the practical knowledge in molecular biology and placental product preparation. Therefore, the level of ordinary skill in the art is high.
Response to Applicants Arguments Against Brahm
Applicants argue that Brahm is not relevant because “Brahm is directed to a catheter for removing and preparing amniotic fluid material and is wholly unrelated to particulate tissue compositions for treating musculoskeletal disorders. Brahm does not cure the deficiencies of Tseng, Tseng II, and Daniel because it neither teaches nor suggests a particulate composition comprising AM, CM, and UC in the claimed proportions, nor does it provide any motivation to combine these tissues.”
Brahm is used to teach claim 41 which recites, “detecting the therapeutically effective amount of the particulate composition in the joint at least 60 days after administration.” Like the Tseng and Daniel references, Brahm in Example 3 teaches the placement of a placental construct within the body to repair a musculoskeletal disorder (Paragraphs 133-134 of Brahm). Paragraph 134 states that after the placental construct was placed, “Monthly follow-up visits were planned and the patient was monitored for healing and/or complications.” The placental construct was placed in an area which was then monitored. These follow up visits detect the therapeutically effective amount of the particulate composition in the affected area at least 60 days after administration by monitoring the area for healing and complications and checking the extension/movement of the area which was impacted by tennis elbow/a musculoskeletal disorder (Paragraphs 132-134 of Brahm). Brahm is appropriate for teaching claim 41. Because the Tseng, Tseng II, and Daniel references were not deficient in their teachings as argued above, Brahm is not defective.
Conclusion
All claims stand rejected.
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 LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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