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 . 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.
Priority
The instant application is a continuation of US application no. 16/976,671 filed on 08/28/2020, which is a 371 of PCT/AU2019/050163 filed on 02/27/2019 and claims foreign priority to Australian application no. AU2018900650 filed on 02/28/2018. The certified copy of the foreign priority application in US application no. 16/976,671 is acknowledged.
Status of the Claims
The claim amendments and remarks filed on 12/29/2025 is acknowledged. Claims 1, 19, and 37 are amended. Claims 2-3, 8-10, 12-13, 15-18, 20-22, 24-25, 27-31, 33-36, and 38-40 are cancelled. Claims 41-42 are newly added.
Accordingly, claims 1, 4-7, 11, 14, 19, 23, 26, 32, 37, and 41-42 are pending and being examined on the merits herein.
Withdrawn Rejections
The 35 USC 112(b) rejection over claim 32 is withdrawn because claim 32 is now cancelled.
The 35 USC 112(a) rejection over claims 1, 4-7, 11, 14, 19, 23, 26, 32-33, and 38 because the term “osteolysis” is now longer excluded from the patient population, and claims 33 and 38 are now cancelled.
The 35 USC 103 rejection over Oishi in view of Mcilwraith and Cullis-Hill for claims 1, 4-5, 7, 19, 23, and 26 over Maheshwari in view of Mcilwraith and Cullis-Hill for claims 1 and 6, over Oishi in view of Mcilwraith, Cullis-Hill, and Metcalfe for claims 11 and 14, and over Oishi in view of Mcilwraith, Cullis-Hill, and Vas for claim 32 are withdrawn because the term “osteolysis” is now no longer excluded from the patient population, which has changed the scope of the claims. Furthermore, while Mcilwraith and Oishi both teach resolving hemarthrosis in a post-operative joint, an ordinary skilled artisan would not have a reasonable expectation of success in using the PPS of Mcilwraith for the treating the underlying knee condition in Oishi. Here, Oishi discloses that the hemarthrosis occurred as a result of a polyploid mass of vascular hypertrophic synovium, whereas Mcilwraith only discloses the use of PPS to resolve hemarthrosis due to loss of articular cartilage following arthroscopic surgery.
The 35 USC 103 rejection over Oishi in view of Mcilwraith and Cullis-Hill for claim 37 is withdrawn because while Mcilwraith and Oishi both teach resolving hemarthrosis in a post-operative joint, an ordinary skilled artisan would not have a reasonable expectation of success in using the PPS of Mcilwraith for the treating the underlying knee condition in Oishi. Here, Oishi discloses that the hemarthrosis occurred as a result of a polyploid mass of vascular hypertrophic synovium, whereas Mcilwraith only discloses the use of PPS to resolve hemarthrosis due to loss of articular cartilage following arthroscopic surgery.
The 35 USC 103 rejection over Oishi in view of Mcilwraith, Cullis-Hill, and Briggs for claims 33 and 38 are withdrawn because claims 33 and 38 are now cancelled.
The following grounds of rejection are maintained or new as necessitated by Applicant’s amendments.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 37 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 37 recites “the human subject is post-operatively not suffering from osteolysis, osteoarthritis, or bone marrow edema in said joint…”.
Applicant discloses that the present invention is based on the surprising finding that pentosan polysulfate (PPS) treatment reduces osteoarthritic pain and post-operative joint pain in a subject as well improve joint function and reduce bone marrow edema lesions with no adverse events reported (see lines 8-13 on page 3 in specification). Furthermore, Applicant discloses several additional embodiments of the method of treating aseptic president post-operative intra-articular joint pain including “wherein the intra-articular aseptic persistent pain is caused by a condition selected from the group comprising: aseptic prosthetic loosening, prosthetic wear, instability, recurrent hemarthrosis, patellar maltracking, tendon rupture and stiffness.” as well as “extra-articular aseptic persistent pain … caused by an extra-articular osteoarthritis …” (see lines 15-21 on page 8 in specification).
However, Applicant has not provided enough disclosure to be in possession of a composition that can be used to treat a human subject who is post-operatively not suffering from osteolysis in said joint because osteolysis was never contemplated in the instant application, and therefore cannot be excluded out. MPEP 2173.05(i) recites “Any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) ("[the] specification, having described the whole, necessarily described the part remaining.").” and “While silence will not generally suffice to support a negative claim limitation, there may be circumstances in which it can be established that a skilled artisan would understand a negative limitation to necessarily be present in a disclosure." Novartis Pharms. Corp. v. Accord Healthcare, Inc., 38 F.4th 1013, 2022 USPQ2d 569 (Fed. Cir. 2022) (quoting Ariad Pharm. Inc. v. Eli Lilly & Co., 589 F.3d 1336, 1351, 94 USPQ2d 1161, 1172).”
Response to Arguments
Applicant states that claims 1 and 37 were amended to remove the term “osteolysis”. However, claim 37 still recites osteolysis, therefore the 35 USC 112(a) rejection over claim 37 is maintained.
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.
Claim(s) 1, 4-5, 7, 19, 23, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Centeno (Regenexx website, published 03/02/2016 in PTO-892) in view of Cullis-Hill et al. (US 20130102562 in IDS filed 06/01/2023).
Centeno discloses that people with severe joint damage, often from osteoarthritis (OA), undergo knee replacement (arthroplasty) as a final option for treatment (first paragraph, page 1). Centeno discloses that total knee replacements improve joint mechanism and lowers pain for many patients, yet relief is not guaranteed. Centeno discloses that long term studies show that 20-30% of these patients continue to report ongoing persistent pain after surgery (second paragraph, page 2).
Centeno discloses several common causes of pain in the knee after surgery (pages 2-4). Centeno discloses that a successful knee replacement depends on a well-fixed implant, metal and cement anchored to living bone. When that bond loosens without infection, a process known as aseptic loosening, the prosthesis can shift microscopically, causing pain. Centeno discloses that aseptic loosening accounts for 78.5% of revision surgeries (see first paragraph under section “Implant Loosening or Wear” on page 3). Centeno discloses that wear particles from the polyethylene insert can speed up loosening. As these fragments accumulate, the body initiates an inflammatory response that leads to bone loss (osteolysis), increases micromotion, and intensifies pain. People often feel deep discomfort during weight-bearing, along with swelling or a sense of instability that worsens over time (see second paragraph under section “Implant Loosening or Wear” on page 3).
Centeno discloses several treatment options for knee pain after surgery which include conservative treatments such as non-steroidal anti-inflammatory medication to reduce synovial inflammation and baseline pain (page 5 section “Treatment Options for Knee Pain after Surgery”).
Even though Centeno suggests the treatment of aseptic persistent post-operative pain in an artificial joint following total joint arthroplasty such as osteolysis associated pain caused by accumulated wear particles from the artificial joint components, Centeno does not teach administering sodium pentosan polysulfate.
Cullis-Hill teaches the use of a cathepsin K activity inhibitor such as oversulfated polysaccharides and exemplifies pentosan polysulfate (see paragraph 0007). Cullis-Hill et al. discloses that the pentosan polysulfate can be in the form of a salt and exemplifies calcium or sodium salts (see paragraph 0043). Cullis-Hill teaches that the patient can be any mammal or a human (see paragraph [0008] and [0054-0056]).
Cullis-Hill discloses that these cathepsin K inhibitors are useful for the treatment and prevention of osteolysis associated with surgical implants and joint replacements as well as excess bone resorption associated with osteolysis (paragraph 0015 and 0018). Cullis-Hill discloses that the term osteolysis generally refers to a problem common to artificial joint replacements such as total hip replacements, total knee replacements and total shoulder replacements. In a total hip replacement, for example, the particles worn off the gliding surface of the ball and socket joint often cause osteolysis. As the body attempts to clean up these loose particles of plastic or metal, the bone grows away from the implant, causing it to loosen (paragraph 0019). Cullis-Hill discloses that prosthetic wear debris-induced peri-implant osteolysis is a major cause of aseptic loosening after total joint replacement. Cathepsin K and tartrate-resistant acid phosphatase were highly expressed in both mononucleated and multinucleated cells associated with the bone surface. Findings suggest that cells expressing the full repertoire of osteoclast phenotypic markers are involved in the pathogenesis of peri-implant osteolysis after total joint replacement. In one study it was found that interface tissue between the bone and loosening total hip implant is acidic and highly osteolytic. It is characterized by the formation of Cathepsin K positive foreign body giant cells. The multinuclear cells induced with pseudosynovial fluid contained active cathepsin K protein and were capable of bone matrix resorption in vitro. The cells were shown to express osteoclast phenotype markers, such as mRNA for cathepsin K, TRAP and calcitonin receptor (paragraph 0115).
Furthermore, Cullis-Hill further teaches oral dosages such as 2 mg/kg bodyweight that can be administered at one time or intermittently to reduce any effects of toxicity. (see paragraphs [0030-0032]) as well as subcutaneous injection (see paragraph [0051]).
It would have been prima facie obvious before the effective filing date of the claimed invention to have identified a human subject suffering from persistent knee pain following knee arthroplasty due to osteolysis caused by accumulated wear particles from the artificial joint components as disclosed in Centeno and to further administer the sodium pentosan polysulfate at 2 mg/kg bodyweight as disclosed in Cullis-Hill to treat this osteolysis and alleviate the associated pain. One of ordinary skill in the art could have combined prior art elements according to known methods to yield predictable results because Centeno establishes that a common cause of persistent joint pain after a joint arthroplasty is due to the accumulation of wear particles from the artificial joint components which can cause the body to initiate an inflammatory response that leads to bone loss (osteolysis), increase micromotion, and intensify pain, and Cullis-Hill establishes a method of treating this osteolysis associated with surgical implants and joint replacements by administering a cathepsin K inhibitor such as sodium pentosan polysulfate.
Furthermore, even though the combined references described above do not explicitly disclose that the post-operative joint pain is treated using sodium pentosan polysulfate, this pain treatment would flow naturally from following the suggestions of the prior art because Cullis-Hill provides a method to treat osteolysis associated with surgical implants and joint replacements using the same effective amounts of sodium pentosan polysulfate, and Centeno establishes the association between joint pain and osteolysis following a joint arthroplasty. Therefore, by treating the osteolysis as described above, the treatment of the associated post-operative joint pain would flow naturally.
MPEP 2145 II recites “The fact that appellant 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." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter.m 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.").” In regards to instant claim 26, an ordinary skilled artisan could have performed routine optimization to arrive at the recited treatment regimen of once daily or twice or thrice weekly based on Cullis-Hill disclosing that the sodium pentosan polysulfate can be administered at one time or in intermittent dosages to reduce any effects of toxicity. See MPEP 2144.05 II.
Claim(s) 6 is rejected under 35 U.S.C. 103 as being unpatentable over Centeno (Regenexx website, published 03/02/2016 in PTO-892) in view of Cullis-Hill et al. (US 20130102562 in IDS filed 06/01/2023), as applied to claim 1 above, and further in view of Vasso et al. (Joints, 2017 in PTO-892).
The combined teachings of Centeno and Cullis-Hill are described above and teach the method of claim 1 as discussed.
The combined references, however, do not disclose a joint arthroplasty that is a partial joint arthroplasty such as a partial knee arthroplasty.
Vasso discloses the modes of failure of unicompartmental (partial) knee arthroplasty (UKA) (see Abstract). Vasso discloses that despite the excellent success rates of the modern UKA, results of knee replacement registries still shows a relatively high revision and failure rate for UKA, especially when compared with traditional total knee arthroplasty (TKA) (Abstract).
Vasso discloses the various causes of UKA failure (right column page 44 through left column page 46). Vasso discloses that causes such as aseptic mechanical loosening and/or polyethylene wear can produce wear-induced periprosthetic osteolysis (due to an increased asymmetrical loading), with a further increase of the component subsidence and/or loosening (see first paragraph under section “Aseptic Mechanical Loosening” and first paragraph under section “Polyethylene Wear” on page 45).
It would have been prima facie obvious before the effective filing date of the claimed invention to have to treated a patient who has wear-induced periprosthetic osteolysis following unicompartmental (partial) knee arthroplasty as disclosed in Vasso by applying the modified treatment method as disclosed by the combined teachings of Centeno and Cullis-Hill described above. One of ordinary skill in the art could have combined prior art elements according to known methods to yield predictable results because the combined teachings of Centeno and Cullis-Hill establishes using sodium pentosan polysulfate to treat osteolysis and its associated pain caused by the accumulation of wear particles from artificial joint components as described above, and Vasso provides further guidance that this wear-induced osteolysis can also occur following unicompartmental (partial) knee arthroplasty.
Claim(s) 11 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Centeno (Regenexx website, published 03/02/2016 in PTO-892) in view of Cullis-Hill et al. (US 20130102562 in IDS filed 06/01/2023), as applied to claim 1 above, and further in view of Metcalfe et al. (BMC Musculoskeletal Disorders, 2012 in PTO-892 dated 08/28/2025) and Kumagai et al. (BMC Clinical Pharmacology in PTO-892).
The combined teachings of Centeno and Cullis-Hill are described above and teach the method of claim 1 as discussed.
The combined references, however, do not disclose wherein the human subject is suffering from an additional arthritic condition further to the post-operative joint pain, in a second joint different from the joint affected by the post-operative pain.
Metcalfe et al. discloses the development of bilateral knee osteoarthritis over a 12 year period using a middle-aged population-based cohort with knee pain at inclusion (see Abstract). Metcalfe et al. discloses that osteoarthritis tends to progress to a bilateral disease and discloses factors such as genetics and inherent mal-alignment as well abnormal loading in the unaffected knee of patients with unilateral knee osteoarthritis, which implies patients with a painful joint may accelerate disease in other joints due to changes in gait (see right column page 1). Metcalfe et al. discloses that a previous study found that eighty-seven percent of patients awaiting total knee replacement (TKR) have radiological evidence of osteoarthritis on the other side (see right column page 1). Metcalfe et al. demonstrates that 24 of the 30 patients with unilateral disease at baseline developed bilateral disease after 12 years (see Abstract) and concludes that a majority of sufferers will eventually develop radiographic disease in both knees (see Abstract).
Kumagai discloses that sodium pentosan polysulfate resulted in cartilage improvement in knee osteoarthritis (Abstract).
Kumagai discloses that twenty patients with varying grades (1 to 3) of knee osteoarthritis were given 2 mg/kg subcutaneous injections of sodium pentosan polysulfate weekly for 6 weeks (Abstract). As demonstrated in Figure 1-2 and Table 1 on pages 3-5, the treatment reduced hydrarthroses quickly in all cases, and clinical assessment including knee flexion, pain while walking, pain after climbing up and down stairs, etc. were all improved significantly, and these clinical improvements continued for almost one year (see Abstract and first paragraph under section “1. Primary outcome measurements” on page 3).
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the treatment method as disclosed by the combined teachings of Centeno and Cullis-Hill described above by treating patients who are additionally suffering from osteoarthritis in the adjacent knee joint based on the disclosures of Metcalfe and Kumagai to arrive at the claimed invention. One of ordinary skill in the art could have combined prior art elements according to known methods to yield predictable results because Metcalfe discloses that a majority of patients who have osteoarthritis in one knee and awaiting total knee arthroplasty in that knee had evidence of osteoarthritis in the adjacent knee and concludes that a majority of patients who have knee osteoarthritis in one knee will likely develop the same condition in the other adjacent knee, and Kumagai provides guidance that sodium pentosan polysulfate is also useful for the treatment of knee osteoarthritis.
Claim(s) 32 is rejected under 35 U.S.C. 103 as being unpatentable over Centeno (Regenexx website, published 03/02/2016 in PTO-892) in view of Cullis-Hill et al. (US 20130102562 in IDS filed 06/01/2023), as applied to claim 1 above, and further in view of Vas et al. (Pain Medicine, 2014 in PTO-892 dated 08/28/2025).
The combined teachings of Centeno and Cullis-Hill are described above and teach the method of claim 1 as discussed.
The combined references, however, do not disclose wherein pain in a human patient is reduced as determined by using the numerical rating scale (NRS).
Vas et al. discloses the successful management of chronic postsurgical pain following total knee replacement (see Abstract). Vas et al. demonstrates that pain relief was observed based on changes in pain as assessed on the Numeric Rating Scale (see Abstract).
It would have been prima facie obvious before the effective filing date of the claimed invention to include in the modified method as disclosed by the combined teachings of Centeno and Cullis-Hill described above a method to assess postoperative joint conditions by a numerical rating scale as disclosed in Vas to arrive at the claimed invention. One of ordinary skill in the art could have combined prior art elements according to known methods to yield predictable results because Vas et al. demonstrates the use of the numerical rating scale to assess the improvement in knee joint pain following a knee replacement surgery. Therefore, an ordinary skill artisan would have predictably considered implementing the numerical rating scale joint assessment disclosed in Vas to determine the results of the treatment of post-operative joint pain in the modified method described above.
Furthermore, an ordinary skilled artisan could further expect an improvement in pain according to this score assessment because even though the combined references described above do not explicitly disclose that the post-operative joint pain is improved using sodium pentosan polysulfate, this assessed pain improvement would flow naturally from following the suggestions of the prior art because Cullis-Hill provides a method to treat osteolysis associated with surgical implants and joint replacements using the same effective amounts of the sodium pentosan polysulfate, and Centeno establishes the association between joint pain and osteolysis following a joint arthroplasty. Therefore, by treating the osteolysis as described above, the improvement in the associated post-operative joint pain as assessed by the recited pain score assessment would flow naturally.
MPEP 2145 II recites “The fact that appellant 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." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter.m 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.").
Claim(s) 41-42 are rejected under 35 U.S.C. 103 as being unpatentable over Centeno (Regenexx website, published 03/02/2016 in PTO-892) Cullis-Hill et al. (US 20130102562 in IDS filed 06/01/2023), Metcalfe et al. (BMC Musculoskeletal Disorders, 2012 in PTO-892 dated 08/28/2025) and Kumagai et al. (BMC Clinical Pharmacology in PTO-892).
The teachings of Centeno are as described above.
Even though Centeno suggests the treatment of aseptic persistent post-operative pain in an artificial joint such as osteolysis associated pain caused from aseptic loosening of artificial joint components, Centeno does not teach administering sodium pentosan polysulfate as well as wherein the human subject is suffering from an additional arthritic condition further to the post-operative joint pain, wherein the additional arthritic condition is selected from the recited group such as osteoarthritis.
The independent teachings of Cullis-Hill, Metcalfe, and Kumagai are described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have identified a human subject suffering from persistent knee pain following knee arthroplasty due to osteolysis caused by accumulated wear particles from the artificial joint components as disclosed in Centeno and to further administer the sodium pentosan polysulfate at 2 mg/kg bodyweight as disclosed in Cullis-Hill to treat this osteolysis and alleviate the associated pain. One of ordinary skill in the art could have combined prior art elements according to known methods to yield predictable results because Centeno establishes that a common cause of persistent joint pain after a joint arthroplasty is due to the accumulation of wear particles from the artificial joint components which can cause the body to initiate an inflammatory response that leads to bone loss (osteolysis), increase micromotion, and intensify pain, and Cullis-Hill establishes a method of treating this osteolysis associated with surgical implants and joint replacements by administering a cathepsin K inhibitor such as sodium pentosan polysulfate.
Furthermore, even though the combined references described above do not explicitly disclose that the post-operative joint pain is treated using sodium pentosan polysulfate, this pain treatment would flow naturally from following the suggestions of the prior art because Cullis-Hill provides a method to treat osteolysis associated with surgical implants and joint replacements using the same effective amounts of sodium pentosan polysulfate, and Centeno establishes the association between joint pain and osteolysis following a joint arthroplasty. Therefore, by treating the osteolysis as described above, the treatment of the associated post-operative joint pain would flow naturally.
MPEP 2145 II recites “The fact that appellant 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." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter.m 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.").”
Additionally, it would have been prima facie obvious before the effective filing date of the claimed invention to have further modified the treatment method as disclosed by the combined teachings of Centeno and Cullis-Hill described above by treating patients who are additionally suffering from osteoarthritis in the adjacent knee joint based on the disclosures of Metcalfe and Kumagai to arrive at the claimed invention. One of ordinary skill in the art could have combined prior art elements according to known methods to yield predictable results because Metcalfe discloses that a majority of patients who have osteoarthritis in one knee and awaiting total knee arthroplasty in that knee had evidence of osteoarthritis in the adjacent knee and concludes that a majority of patients who have knee osteoarthritis in one knee will likely develop the same condition in the other adjacent knee, and Kumagai provides guidance that sodium pentosan polysulfate is also useful for the treatment of knee osteoarthritis.
Response to Arguments
Applicant’s arguments in the response filed on 12/29/2025 have been fully considered in so far
as they apply to the rejections of the instant office action, but were not persuasive.
Applicant presents several arguments against the previous rejections that relied on either Oishi or Maheshwari as the primary reference and Mcilwraith and Cullis-Hill as secondary references. Furthermore, Applicant states that the teachings of Metcalfe or Vas do not remedy the deficiencies in the references described above and do not teach administering the sodium pentosan polysulfate for treating the recited post-operative joint pain.
Applicant’s argument described above were not found persuasive because the new rejections do no cite Oishi, Maheshwari, or Mcilwraith. Therefore, Applicant’s arguments regarding these references are rendered moot. Furthermore, the teachings of Metcalfe and Vas are relied on upon to establish a patient further having osteoarthritis in the adjacent knee and the use of a Numerical Rating Scaling to quantify pain relief following total knee arthroplasty, respectively, and not for establishing the use of sodium pentosan polysulfate to treat the post-operative joint pain.
Applicant states that Cullis-Hill is silent on pain and analgesic activity. Applicant states these terms are not present in Cullis-Hill, and as previously argued, Cullis-Hill aims to treat and resolve a pathophysiological condition, that is osteolysis and bone resorption, and not pain. Applicant states in contrast, their method is directed to treating joint pain as a direct result of joint arthroplasty. Applicant states that since Cullis-Hill is silent on pain, there is no motivation to select Cullis-Hill for administering sodium pentosan polysulfate to treat post-operative joint pain in humans.
Applicant’s argument described above was not found persuasive because Centeno in the new rejection establishes the association between joint pain and osteolysis caused by accumulated wear particles from the artificial joint components following total joint arthroplasty as described above. Furthermore, Cullis-Hill teaches the treatment of osteolysis associated with surgical implants and joint replacements by administering an effective amount of a cathepsin K inhibitor such as sodium pentosan polysulfate. Therefore, even though the combined references described above do not explicitly disclose that the post-operative joint pain is treated using sodium pentosan polysulfate, the treatment of the associated post-operative joint pain would flow naturally from following the suggestions of the prior art as described above.
Applicant states that in the interview conducted on 12/08/2025, the Examiner indicated potential allowable subject matter in claim 11 but would require additional search and consideration.
Claim 11 is directed to a patient who is additionally suffering an adjacent joint knee condition. Example 1 (pages 42-45) in the specification demonstrates the effects of pentosan polysulfate on clinical outcomes of pain and function in a patient suffering left knee osteoarthritis and from persistent pain in the right knee following total right knee arthroplasty. Here, as seen in Table 1 on page 44, the patient had reduced pain in the left knee osteoarthritis according the NRS and Lysholm Knee score after being administered 2 mg/kg of pentosan polysulfate twice a week for three weeks. Furthermore, the instant specification discloses a surprising effect in that the post-operative aseptic, persistent pain in the right artificial knee joint also subsided/stopped and went to zero and that this surprising improvement in pain response was not consequent to the improvement in the left knee or associated with rehabilitation or compensatory to the improvement in the left knee (page 45 lines 5-8).
Upon reconsideration, Applicant’s unexpected result described in the specification does not appear to be unexpected in view of the prior art because as described above, sodium pentosan polysulfate has therapeutic effects for pain in knee osteoarthritis as disclosed in Kumagai, and the combined teachings of Centeno and Cullis-Hill also provide guidance that sodium pentosan polysulfate can be used to treat osteolysis and its associated pain caused by accumulated wear particles from the artificial joint components following total joint arthroplasty as described above. Furthermore, Metcalfe suggests the patient population described in the specification because Metcalfe discloses that a majority of patients who have osteoarthritis in one knee and awaiting total knee arthroplasty in that knee had evidence of osteoarthritis in the adjacent knee and concludes that a majority of patients who have knee osteoarthritis in one knee will likely develop the same condition in the other adjacent knee.
Therefore, while the prior art does not explicitly teach treating pain in both knee conditions at the same time using sodium pentosan polysulfate, an ordinary skilled artisan could have reasonably expected that administering the sodium pentosan polysulfate to treat the osteolysis and associated pain in a post-operative knee joint would also naturally treat the pain from an osteoarthritis condition in the adjacent knee joint because the combined teachings of Centeno, Cullis-Hill et al., Metcalfe et al, and Kumagai et al. suggest the administration of sodium pentosan polysulfate to this patient population, and furthermore, the prior art establishes that this compound can be used to alleviate pain for both knee conditions as described above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1, 4-7, 11, 14, 19, 23, 26, 32, 37, and 41-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,701,382 (‘382).
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘382 recites a method for the treatment of aseptic post-operative intra-articular joint pain resulting from a joint arthroplasty performed on a mammal, the method comprising the steps of: (i) identifying the mammal as suffering from aseptic post-operative intra-articular joint pain which is the direct result of a joint arthroplasty, wherein the mammal is post-operatively not suffering from osteolysis, osteoarthritis or bone marrow edema in said joint; and (ii) administering, within 12 months post-operatively, an amount of pentosan polysulfate or an acceptable salt thereof, to the mammal, effective to alleviate said aseptic post-operative intra-articular joint pain resulting from the joint arthroplasty. Claim 3 of ‘382 recites herein the at least one articulating joint is a knee. Claim 4 of ‘382 recites the joint arthroplasty is a partial joint arthroplasty selected from the group consisting of: a partial ankle arthroplasty, a partial elbow arthroplasty, a partial finger arthroplasty, a partial hip arthroplasty, a partial knee arthroplasty, a partial shoulder arthroplasty, and a partial wrist arthroplasty. Claim 5 of ‘382 recites the joint arthroplasty is a total joint arthroplasty selected from the group consisting of: a total ankle arthroplasty, a total elbow arthroplasty, a total finger arthroplasty, a total hip arthroplasty, a total knee arthroplasty, a total shoulder arthroplasty, and a total wrist arthroplasty. Claim 7 of ‘382 recites wherein the persistent pain is intra-articular persistent. Claim 8 of ‘382 recites the mammal is suffering from an additional arthritic condition further to the post-operative joint pain, in a second joint different from the joint affected by the post-operative pain, wherein the additional arthritic condition is selected from the group consisting of: rheumatic arthritis, osteoarthritis and degenerative osteoarthritis. Claim 9 of ‘382 recites the second joint is one knee joint and the joint affected by the post-operative pain is another knee joint. Claim 10 of ‘382 recites he pentosan polysulfate (PPS) is selected from the group consisting of: the sodium salt of pentosan polysulfate (NaPPS), the magnesium salt of pentosan polysulfate (MgPPS), the calcium salt of pentosan polysulfate (CaPPS), and the zinc salt of pentosan polysulfate (ZnPPS). Claim 11 of ‘382 recites administering the polysulfated polysaccharide or the acceptable salt thereof to the mammal in an effective amount of about 0.5 to about 2 mg/kg; about 0.5 to about 1 mg/kg; about 1.0 to about 1.5 mg/kg or about 1.5 to about 2.0 mg/kg of the mammal per dose or wherein the effective amount is a fixed dose in the range of about 25 mg to about 4000 mg. Claim 13 of ‘382 recite the treatment is: by administering a subcutaneous (SC) injection, an intramuscular (IM) injection, intravenous (IV) injection, intra-articular (IA) injection or a peri-articular injection; by topical administration; via suppositories or by oral administration. Claim 14 of ‘382 recites administration to a human patient is by dosing in a treatment regimen once daily, twice weekly or thrice weekly. Claim 16 of ‘382 recite pain in a human patient is reduced as determined by using the numerical rating scale (NRS). Claim 17 of ‘382 recites the function of the knee joint with post-operative pain and/or function of the knee joint with the additional arthritic condition in a human patient is improved as determined by using the Lysholm Knee Score.
The claims of ‘382 recite all of the same limitations in the instant claims such that an ordinary skill artisan could readily envision the instant invention. Furthermore, the claims of ‘382 recite an additional limitation of “administering, within 12 months post-operatively” in the method. However, this added limitation is still fully encompassed within the scope of the instant claims. Therefore, the claims of ‘382 anticipate all of the instant claims.
Response to Arguments
Applicant requests the non-statutory double patenting rejection to be held in abeyance until allowable subject matter has been found in the instant application.
Since allowable subject matter has not been identified, the non-statutory double patenting rejection over ‘382 is maintained.
Conclusion
No claim is found allowable.
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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/D.H.C./Examiner, Art Unit 1693 /SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693