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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claimed in claims 1-2 and 4-10 in the reply filed on 7/9/25 was previously acknowledged. Election was made of osteoarthritis.
In the reply filed 12/10/25, Applicants amended claims 1 and canceled claims 2 and 4-10.
Claim 3 is withdrawn from further consideration pursuant to 37 CFR 1.142(b)
as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claims 1 and 3 are pending.
Claims 1 is under consideration.
Claim Objections-Withdrawn
The objection to claims 2, 4 and 10 is withdrawn due to cancelation of the claims.
Claim Rejections - Withdrawn
The rejection of claims 1-2, 4-10 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treatment of osteoarthritis with the GDF-5 mutant protein with the amino acid exchange R399E does not reasonably provide enablement for treatment or prevention of all cartilage defects is withdrawn due to amendment of claim 1 and cancelation of claims 2 and 4-10.
The rejection of claim 2 is under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn due to cancelation of the claim.
The rejection of claims 1-2, 5, 8 and 9 under 35 U.S.C. 102(a)(1) as being anticipated by Ploger et al. (USPN 9,718,867; 8/1/2017, cited on IDS) is withdrawn due to amendment of claim 1 to include “intraarticular injection” and cancelation of claim 2 and 4-10.
The rejection of claims 1-2, 5-6, 8 and 9 rejected under 35 U.S.C. 103 as being unpatentable over Ploger et al. (USPN 9,718,867; 8/1/2017) in view of Muurahainen et al. (Osteoarthritis and Cartilage Vol 24, Supplement 1, S4 April 2016) is withdrawn due to cancelation of claims 2 and 4-10.
Claim Rejections - 35 USC § 112-NEW
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. This is a NEW rejection necessitated by amendment of the claim.
The term “rapid relief” in claim 1 is a relative term which renders the claim indefinite. The term “rapid relief” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In particular, the specification does not define a standard for determining what constituted rapid relief of pain. Absent such guidance, “rapid relief” is subjective and depends on individual interpretation.
Claim Rejections - 35 USC § 103-Maintained
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Ploger et al. (USPN 9,718,867; 8/1/2017, cited in IDS) in view of Parrish et al. (Osteoarthritis and Cartilage 25(2017) 554-560, cited on IDS). Please note this rejection has been modified due to amendment of claim 1.
Ploger et al. teach GDF-5 related proteins with improved capability of inducing cartilage formation (Abstract). Ploger et al. teach and claim the use of GDF-5 mutants for treatment of a disease where cartilage formation is desired and treatment of cartilage defects, such as osteoarthritis (claims 7-8 and col 13,line 42).
With respect to the limitation “administering to said patient a GDF-5 mutant protein with the amino exchange R399E”, Ploger et al. teach and claim GDF-5 with the exchange R399E (col. 8, line 33; Fig. 5; Ex. 3 (col. 16); Table 1 and claims 1 and 10).
Ploger et al. do not teach intra-articular administration of GDF-5 R399E. However, the teachings of Parrish et al. cure this deficiency.
Parrish et al. teach intra-articular injection of rhGDF-5. Parrish et al. teach intra-articular rhGDF-5 supplementation can reverse OA disease progression (Abstract-Conclusions).
It would have been obvious to a person of ordinary skill in the art to administer the GDF-5 R399E of Ploger et al. intra-articularly as taught by Parrish et al. for treatment of OA. A person of ordinary skill in the art would have a motivation to administer the agent to the affected joint because Parrish et al. teach supplementation to the affected joint reversed OA disease progression. There is a reasonable expectation of success given techniques for intra-articular administration are well known in the art and Parrish et al. teach the benefits for OA treatment.
With respect to the limitation “pain associated with osteoarthritis” and “wherein the GDF-5 mutant protein is effective for rapid relief of pain associated with osteoarthritis”, Ploger et al. does not disclose treatment of pain. However, the composition (GDF-5 with R399E mutation) from Ploger et al. administered intraarticularly would necessarily have all of the activities and properties of the composition of claim 1. The MPEP § 2112 states: “Once a reference teaching product appearing to be substantially identical is made the basis of a rejection, and the Examiner presents evidence or reasoning tending to show inherency, the burden shifts to the Applicant to show an unobvious difference ‘[t]he PTO can require an Applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on inherency’ under 35 U.S.C. 102, on prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same…[footnote omitted].” The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzqerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430,433- 34 (CCPA 1977)).” In other words, Ploger et al. and Parrish et al. teach administering the same composition (GDF-5 mutant with R399E exchange) to the same patient population (patient in need of treatment of cartilage defects such as OA) in the same manner (intraarticular injection), therefore the pain would necessarily be rapidly reduced. Moreover, MPEP 2112.01 states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Importantly, MPEP 2112 states: ““[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999) and “There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency)”.
Response to Arguments
Applicant's arguments filed 12/10/25 have been fully considered but they are not persuasive. Applicants argue that experimental data demonstrates that R399E surprisingly provided rapid and long lasting pain relief within hours of intraarticular administration as evidenced by multiple animal models (see Ex.3, 3). Applicants argue that the rapid onset of action coupled with its sustained effects represents an advantage over other therapies that require prolonged treatment times. Applicants argue these results are unexpected and non-obvious. Applicants argue that Ploger does not provide any teaching or suggestion that the GDF-5 R399E would have any immediate analgesic effect and one of ordinary skill in the art would not have any basis to expect that the intraarticular injection of the mutant would yield rapid and long lasting pain relief. Applicants argue that Parrish’s studies are directed to the use of rhGDF-5 as a therapeutic and non the mutated form instantly claimed. Applicants argue that Parrish points out that mutations of GDF-5 also cause chondrodysplasias. Applicants argue that thereof, Parrish effectively teaches away from using mutated GDF-5 protein as a therapeutic molecule. Applicants argue that this teaching away further reinforces the assertion that the surprising biological effect resulting from the intraarticular injection of a mutated version of GDF-5 could not have been anticipated based on Parrish’s disclosure.
These arguments were considered but are not persuasive. The Examiner agrees that Ploger does not disclose treatment of pain. However, Ploger discloses administering GDF-5 R399E to a subject with osteoarthritis. The argument of unexpected results is not persuasive because the pain relief would necessarily occurred in the prior art patients, even if the prior art did not measure or report it. The MPEP § 2112 states: “Once a reference teaching product appearing to be substantially identical is made the basis of a rejection, and the Examiner presents evidence or reasoning tending to show inherency, the burden shifts to the Applicant to show an unobvious difference ‘[t]he PTO can require an Applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on inherency’ under 35 U.S.C. 102, on prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same…[footnote omitted].” The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzqerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430,433- 34 (CCPA 1977)).” In other words, Ploger and Parrish teach administering the same composition (GDF-5 mutant with R399E exchange) to the same patient population (patient in need of treatment of cartilage defects such as OA) in the same manner (intraarticular injection) therefore the pain would necessarily be rapidly reduced. Moreover, MPEP 2112.01 states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Importantly, MPEP 2112 states: ““[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999) and
Importantly, the MPEP 2112 II. states that the inherent feature need not be recognized at the relevant time: “There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency)”. In the instant case, the same composition administered to the same population would have the same results, even if the result was not recognized at the relevant time. Additionally, the MPEP 2112.01 states: When the structure recited in the reference is substantially identical, the claimed properties or functions are presumed to be inherent. The teachings of Parrish do not teach away from the claimed invention. The MPEP 2145 states: A prior art reference that “teaches away” from the claimed invention is a significant factor to be considered in determining obviousness. However, “the nature of the teaching is highly relevant and must be weighed in substance. A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In the instant case, a mutation associated with a congenital skeletal disorder does not mean that all GDF-5 mutants are undesirable therapeutic agents. Parrish merely states that certain naturally occurring mutations in GDF-5 are associated with chondrodysplasia and is just descriptive background information in the article. The information is in no way a warning or teaching away from therapeutic use of engineered mutants. Parrish merely discusses genetic mutations associated with disease and not therapeutic administration of those mutants. Importantly, the primary reference clearly teaches the mutant for osteoarthritis treatment.
For the reasons presented above, the rejection is maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 TARA L MARTINEZ whose telephone number is (571)270-1470. The examiner can normally be reached Mon-Fri 8:00-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TARA L MARTINEZ/ Examiner, Art Unit 1654