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 .
The preliminary amendment filed 5/20/24 is acknowledged.
Claims 1-17 are pending and under examination.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 112
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.
Claims 1-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of reducing joint pain by impacting a 3D shape change of bone underlying articular cartilage in a joint in a subject having osteoarthritis and a method to delaying, arresting, or reversing naturally occurring aging of a joint in a subject having osteoarthritis, said methods comprising locally injecting by intra-articular injection into the joint of the patient a therapeutically effective amount of a formulation comprising a pharmaceutically acceptable injectable carrier, and a pharmaceutically active peptide selected from the group consisting of SEQ ID NOs: 1-6, does not reasonably provide enablement for methods comprising any subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required, are set forth in In re Wands 8 USPQ2d 1400. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art and (8) the breadth of the claims.
(4) The nature of the invention and (8) The breadth of the claims:
The nature of the invention is a method of reducing joint pain by impacting a three-dimensional shape change of bone underlying articular cartilage in a joint, comprising (a) obtaining and measuring a first image of a bone shape underlying articular cartilage at the joint of a patient, (b) locally injecting into the joint of a patient a therapeutically effective amount of a formulation comprising a pharmaceutically acceptable, injectable carrier, and a pharmaceutically active peptide characterized by impacting shape change of bone underlying articular cartilage in the patient whereby shape change of the bone underlying articular cartilage in the patient is impacted; (c) obtaining and measuring a second image of the bone shape underlying articular cartilage after the injecting; and (d) comparing the measurement of the bone shape in the first image obtained in step (a) with the measurement of the bone shape in the second image obtained in step (c); and (e) determining the need for additional injections based on whether the bone shape significantly changed from the injecting based on the comparing step (d); wherein: the peptide is a peptide selected from the group consisting of the peptide of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6.
Claim 15 is drawn to a method to delaying, arresting, or reversing naturally occurring aging of a joint, comprising: (a) measuring bone shape of a joint of a patient; (b) locally injecting by intra-articular injections into the joint of the patient a therapeutically effective amount of a formulation comprising a pharmaceutically acceptable, injectable carrier, and a peptide; (c) remeasuring the bone shape of the joint; and (d) comparing a measurement obtained with a measurement obtained in (c) prior to locally injecting in step (b) to determine if the bone shape significantly changed due to the injecting, wherein the peptide is the peptide of SEQ ID NO.: 1 administered in amount in a range of 50-400mg.
Therefore, the nature of the invention is a chemical case, where there is natural unpredictability in performance of certain species or sub-combinations other than those specifically enumerated; see MPEP 2163. Accordingly, it is the Office’s position that undue experimentation would be required to practice the claimed methods, with a reasonable expectation of success, because it would not be predictable from the disclosure of any one particular species what other species may or may not work; see MPEP 2164.03.
Although the specification discloses that subjects with osteoarthritis are encompassed by the claims, the claims are not limited to subjects with osteoarthritis and broadly encompass any subject.
(5) The state of the prior art and (7) The predictability or unpredictability of the art:
Christensen et al. (JBMR Plus, 2020, Vol. 4(8), e10378) discuss matrix extracellular phosphoglycoprotein (MEPE), the protein from which the peptides of SEQ ID NOs: 1-6 are derived. Christensen et al. teach that MEPE has a high level of phosphorylation, particularly high density in the ASARM motif, provides an important basis for understanding of structural and function interdependencies in mineralization and phosphate homeostasis (See abstract). Although Christensen et al. teach that conserved serine residues and the ASARM region that are required for MEPE to maintain its function (e.g., act as an inhibitor of mineralization), there is no information that one of skill in the art could use to predict which peptides of MEPE would have the claimed function(s).
As noted above, the claims are not limited to a particular patient population. Li et al. (Arthritis Res. Ther., 2013, Vol. 15(6), article 223) discuss microstructural changes in subchondral bone in osteoarthritis. Li et al. teach that subchondral bone is a very dynamic structure and is uniquely adapted to the mechanical forces imposed across the joint (See page 2). Li et al. teach that in addition to bone density patterns and mechanical properties, subchondral bone also dynamically adjusts trabecular orientation and scale parameters in a precise relationship with principal stress (See page 2). Li et al. teach that mechanical stress also modifies the contour and shape of subchondral bone by means of bone modeling and remodeling (See page 2). Li et al. teach that despite the focus on the contribution of subchondral bone to the pathogenesis of OA for over four decades, there remains a controversy over its role: is it a trigger factor or a secondary consequence of cartilage degeneration? (See page 5). Li et al. teach that despite the numerous pathophysiological alterations detected in subchondral bone with OA, there is still a lack of clear understanding of the mechanisms underpinning their phenomena and how these different aspects are interrelated to each other (See page 9). Thus, it is unpredictable what effects it may cause if the shape of the subchondral bone is changed in a joint of a subject without osteoarthritis. The scope of patent protection sought by Applicant as defined by the claims fails to correlate reasonably with the scope of enabling disclosure set forth in the specification.
6) The amount of direction or guidance provided by the inventor; 7) The existence of working examples:
The working examples teach that TPX-100, a peptide of SEQ ID NO: 1 is a synthetic peptide consisting of 23 amino acids, derived from human matric extracellular phosphoglycoprotein. The working examples demonstrate that administration of TPX-100 to patients resulted in clinically meaningful and statistically significant improvements in the knees based upon the KOOS subscales. The working examples teach that change in periarticular bone area and 3D bone shape was measured by MRI and knees treated with TPX-100 demonstrated less pathological bone area increase as compared to control knees, with a trend toward statistical significance. The working examples demonstrate that in the lateral femur and lateral and medial patella, pathological bone area increase in the first 6 months was nearly zero in treated knees in the first 6 months, with slower increase at 12 months compared with control knees. The working examples teach that these data indicate that treatment of knee OA with TPX-100 delays, arrests, or even reverses periarticular bone area in the knees associated with onset and progression of OA. The working examples teach that 3D periarticular bone shape change of femurs as quantified by the bone shape score showed a statistically significant difference in favor of treated knees compared to control knees at both 6 and 12 months. The working examples teach that 3d periarticular change bone shape changes in tibia and patella also demonstrated slower changes in treated knees compared to control knees, although the results were not statistically significant. The working examples teach that tibiofemoral cartilage thickening/stabilization significantly correlated with KOOS ADL/WOMAC function improvement in treated knees, but not in control knees. The working examples teach that slower patella bone shape change significantly correlated with a reduction in pain frequency in treated knees, but not in control knees.
Apart from a working example demonstrating that peptide TPX-100 (SEQ ID NO: 1) significantly reduced, arrested, or even reversed pathological periarticular bone structure change in multiple compartments in the knee joint of patients with OA, and provided critical benefits to patients including improvements in knee function and pain, the Applicant has not provided substantive evidence of treatment of any other patient population. Because the claims encompass any subject, a demonstration of efficacy of a single peptide in a patient with osteoarthritis does not provide support for the breadth of the claims.
Taken together, the art demonstrates that the treatment of joint disorders, in particular osteoarthritis, is highly unpredictable. Moreover, the art does not provide guidance for all subjects encompassed by the claimed method. Accordingly, it follows that the patient population(s) in which the method can be practiced can only be identified empirically. This constitutes undue experimentation. Therefore, given the lack of guidance in the art, the lack of working examples commensurate in scope to the claimed invention and the unpredictability of treating cancer, the specification, as filed does, not provide enablement for the claimed genus of peptides and subjects.
Applying the above test to the facts of record, it is determined that 1) no declaration under 37 C.F.R. 1.132 or other relevant evidence has been made of record establishing the amount of experimentation necessary, 2) insufficient direction or guidance is presented in the specification with respect to broadly treating any subject with the claimed pharmaceutically active peptides in the claimed methods, 3) the relative skill of those in the art is commonly recognized as quite high (post-doctoral level). One of skill in the art would require guidance, in order to make or use the peptides in a manner reasonable in correlation with the scope of the claims. Without proper guidance, the experimentation to is undue.
The Applicant has not provided sufficient guidance to enable one of skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims broadly including all subjects. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970). Without such guidance, determining peptides that can be used for treating which subjects in the claimed methods is unpredictable and the experimentation left those skilled in the art is unnecessarily and improperly, extensive and undue. See Amgen Inc v Chugai Pharmaceutical Co Ltd. 927 F 2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991) at 18 USPQ2d 1026-1027 and Exparte Forman, 230 U.S.P.Q. 546(Bd. Pat=. App & int. 1986).
In view of all of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention, and thus, the claimed invention does not satisfy the requirements of 35 U.S.C. 112 first paragraph.
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.
Claims 1-14 are 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.
Claim 1 recites "obtaining a first image… obtaining a second image. This limitation is indefinite because it is unclear how the images are obtained. The term "obtain" means to get, acquire or secure something. Under the broadest reasonable interpretation, the phrase obtaining an image could read on acquiring the image visually from a computer screen, or alternatively, the phrase could read on acquiring the image by performing an imaging technique. If Applicant's intends for phrase "obtaining" to encompass performing an imaging technique, the claim should be amended to recite the specific technique for obtaining the first and second image. Given the alternative interpretations of the limitation, there is ambiguity as to the scope of the claim and one of skill in the art would not be apprised of the metes and bounds of the claim. Claims 2-14 do not sure the deficiencies of claim 1, and thus, are included in the rejection.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis 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.
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 1-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Middleton-Hardie et al. (U.S. Patent No. 8,426,558, published April 23, 2013).
Middleton-Hardie et al. teach a method of treating osteoarthritis, comprising: diagnosing an area of patient as being osteoarthritic; administering an intra-articular injection of a therapeutically effective amount of a formulation comprised of a pharmaceutically acceptable carrier and a peptide which is characterized by providing dose dependent generation of cartilage in the area; allowing the formulation to act on the osteoarthritic area; and examining the area of the patient to determine a change in cartilage relative to a time prior to the administering, wherein the peptide comprises the peptide set forth in SEQ ID NO: 21 (See claim 1 and column 13). Middleton-Hardie et al. teach a method of treating a disease such as osteoarthritis by administering a formulation composing SEQ ID NO: 21 locally via intra-articular injection to the area of disease (See column 13 and example 4). It should be noted that the peptide of SEQ ID NO: 21 is identical to the instant SEQ ID NO: 1. Middleton-Hardie et al. teach that the method may include determining an area of a subject which is prone to disease and administering the formulation locally to the area of disease, and may further include not only diagnosing the patient and localizing the area of disease but testing the area to determine the level of disease such as the degree of bending of a joint which can be carried out, and thereafter administering the formulation, allowing the formulation to act on the area, and thereafter retesting the patient to determine the level of improvement in the area such as improvement in the degree of binding of a joint (See column 13). Middleton-Hardie et al. teach that in osteoarthritis, cartilage in the joints is lost that causes significant pain when moving the joints, and this condition is caused by mechanical stress on the joints. Middleton-Hardie et al. teach that osteoarthritis is more common in the aged (See column 13). Middleton-Hardie et al. teach that the bone is patella bone (See example 4). Middleton-Hardie et al. teach that the subject is human (See columns 7 and 8). Middleton-Hardy et al. teach an initial intra-articular injection of the peptide of SEQ ID NO: 1 into the joint, followed by an additional injection of the peptide at 1, 2, and 3 weeks (See example 4 and columns 16 and 30-31). Middleton-Hardie et al. teach that following MR imaging, a gross evaluation was performed of the injected, sham, and control stifle joints with photodocumentation (See column 32). Middleton-Hardie et al. teach that images of the joints were taken with photodocumentation and the joints were grossly evaluated for specific changes relative to the cartilage surfaces (See example 4). Middleton-Hardie et al. teach that treatment with the peptide significantly improved cartilage healing (See example 4). Middleton-Hardie et al. teach administering 5 mg, 25 mg, and 125 mg of the peptide over a period of weeks (See example 4 and column 23). Regarding the limitations “reducing joint pain by impacting a 3D shape change of bone underlying articular cartilage in the affected joint”, and “delaying, arresting, or reversing naturally occurring aging of a joint”, the aforementioned limitations are inherent properties that necessarily flow from administering the peptide to a subject having osteoarthritis. That is, the prior art method administers the same peptide, in the same manner, to the same patient population, and thus, would have the same outcome of impacting a 3D shape change of bone underlying cartilage in an affected joint, and delaying, arresting, or reversing naturally occurring aging of a joint, as recited in the instant claims. "Products of identical chemical composition can not 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. Id.
Middleton-Hardies et al. do not expressly teach obtaining a first image prior to locally injecting the peptide.
However, it would have been obvious to one of skill in the art before the effective filing date of the claimed invention to modify the method of Middleton-Hardie et al. by obtaining a first image prior to injecting the peptide into a joint of the patient given that Middleton-Hardie et al. teach evaluating the joint prior to administering the peptide and thereafter, followed by retesting the subject to determine the level of improvement. Middleton-Hardie et al. also teach imaging the joints following treatment. Thus, it would have been within the capabilities of one of skill in the art to image the joints both prior to and after treatment with the peptide to allow for photographic comparisons of the joint before and after treatment with the peptide to assess efficacy of the peptide. One of ordinary skill in the art would be motivated to image the joints before and after treatment with the peptide because doing so would allow one to determine the level of improvement by comparing images of the joints, and additionally, determine if further treatment is needed.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". The combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-4 and 8-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 12,303,590. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims recite method of reducing joint pain by impacting a three-dimensional shape change of bone underlying articular cartilage in a joint, comprising (a) obtaining and measuring a first image of a bone shape underlying articular cartilage at the joint of a patient, (b) locally injecting into the joint of a patient a therapeutically effective amount of a formulation comprising a pharmaceutically acceptable, injectable carrier, and a pharmaceutically active peptide characterized by impacting shape change of bone underlying articular cartilage in the patient whereby shape change of the bone underlying articular cartilage in the patient is impacted; (c) obtaining and measuring a second image of the bone shape underlying articular cartilage after the injecting; and (d) comparing the measurement of the bone shape in the first image obtained in step (a) with the measurement of the bone shape in the second image obtained in step (c); and (e) determining the need for additional injections based on whether the bone shape significantly changed from the injecting based on the comparing step (d); wherein: the peptide is a peptide selected from the group consisting of the peptide of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6.
The ‘590 claims teach a method of delaying or reducing pathological bone shape change of a subchondral bone in a joint of a patient having osteoarthritis, comprising: (i) obtaining a first image of the subchondral bone using magnetic resonance imaging (MRI), and measuring three-dimensional (3D) bone shape of the subchondral bone from the first MRI image, thereby diagnosing pathological bone shape change of the subchondral bone and osteoarthritis progression in the joint; (ii) administering by local injection into the joint a therapeutically effective amount of a formulation comprising a pharmaceutically active peptide set forth in SEQ ID NO: 1, and a pharmaceutically acceptable, injectable carrier; (iii) obtaining a second image of the subchondral bone using MRI, and measuring 3D bone shape of the subchondral bone from the second MRI image; (iv) comparing the 3D bone shape measured from the first MRI image and the second MRI image, and determining responsiveness of the 3D bone shape change to the peptide injection; and (v) repeating the injection until the pathological bone shape change in the joint is delayed or reduced, wherein the measuring and comparing of 3D bone shape are performed using active appearance modelling (AAM). The ‘590 claims teach wherein the repeating of injection is over a period of weeks, and the pharmaceutically active peptide is administered in an amount in a range of 50 to 400 mg±20%. The ‘590 claims teach wherein the joint is a knee joint. The ‘590 claims teach wherein the subchondral bone is a femur. Thus, the claims of the ‘590 claims anticipate the instant claims, and the claims are not patentably distinct.
Claims 1-17 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 7,888,462 in view of Roemer et al. (Osteoarthritis and Cartilage 24 (2016) 274e289 275).
The ‘846 claims are drawn to a promoting cartilage growth, comprising: determining an area of patient cartilage as being in need of treatment; administering locally to the area, by injection, a therapeutically effective amount of a formulation comprised of a pharmaceutically acceptable carrier and a peptide which is characterized by providing dose dependent generation of cartilage in the area; allowing the formulation to act on the cartilage; and examining the area of the patient to determine a change in cartilage relative to a time prior to the administering wherein the peptide comprises at least 20 and no more than 50 amino acid residues, wherein the sequence has the formula of DLXXXXXNDXXPFXXXXQXF (SEQ ID NO:1), wherein X is any amino acid and the peptide is further characterized by a biological activity which enhances hard tissue growth, and wherein the amino acid may be in the D- or L-conformation. The ‘846 claims teach the administering is by injection selected from the group consisting of subcutaneous, intravenous, intra-arterial, intra-pericardial, and intra-articular injection. The ‘846 claims teach wherein the peptide is further characterized by a biological activity which enhances bone growth. The ‘846 claims teach the determining comprises diagnosing the patent with a form of arthritis chosen from osteoarthritis and rheumatoid arthritis. The ‘846 claims teach the administration is an intra-articular injection of the peptide in an injectable formulation. The ‘846 claims teach the peptide has the amino acid sequence of SEQ ID NO: 21, which is 100% identical to the peptide of SEQ ID NO: 1 of the instant claims.
The ’846 claims do not teach imaging obtaining a first prior to locally injecting the peptide and obtaining a second image after the injecting.
Roemer et al. teach that the art has MRI based semi-quantitative scoring of knee osteoarthritis is a valuable method for performing multi-feature joint assessments and of the whole joint in the clinical environment (See page 274). Roemer et al. teach that semiquantitative MRI assessment of osteoarthritis is a valid, reliable, and responsive which helps investigators to evaluate potential new drugs for osteoarthritis (See abstract and page 287). Roemer et al. teach that these SQ scoring systems have been applied to several interventional clinical trials (See page 288).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to obtain images of the joint before and after administration of the peptide as a means for evaluating the efficacy of the peptide, and to determine if further treatment is needed. Given that the ‘846 claims teach examining the area of the patient to determine a change in cartilage relative to a time prior to the administering, it would be obvious to one of ordinary skill in the art to use a known imaging technique, such as MRI, to determine change in cartilage by comparing images of the joint before and after the administration of the peptide to assess efficacy of the peptide and to determine the need for further treatment. Further, it would have been obvious to measure the bone shape of the joint before and after treatment with the peptide to assess the efficacy of the peptide.
Regarding the limitations “reducing joint pain by impacting a 3D shape change of bone underlying articular cartilage in the affected joint”, and “delaying, arresting, or reversing naturally occurring aging of a joint”, the aforementioned limitations are inherent properties that necessarily flow from administering the peptide to a subject having osteoarthritis. That is, the prior art method administers the same peptide, in the same manner, to the same patient population, and thus, would have the same outcome of impacting a 3D shape change of bone underlying cartilage in an affected joint, and delaying, arresting, or reversing naturally occurring aging of a joint, as recited in the instant claims. "Products of identical chemical composition can not 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. Id.
Claims 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 8,426,558 in view of Roemer et al. (Osteoarthritis and Cartilage 24 (2016) 274e289 275).
The ‘558 claims are drawn to a method of treating osteoarthritis, comprising: diagnosing an area of patient as being osteoarthritic; administering an intra-articular injection of a therapeutically effective amount of a formulation comprised of a pharmaceutically acceptable carrier and a peptide which is characterized by providing dose dependent generation of cartilage in the area; allowing the formulation to act on the osteoarthritic area; and examining the area of the patient to determine a change in cartilage relative to a time prior to the administering, wherein the peptide comprises at least 20 and no more than 50 amino acid residues, wherein the sequence has the formula of DLXXXXXNDXXPFXXXXQXF (SEQ ID NO:1), wherein X is any amino acid and the peptide is further characterized by a biological activity which enhances hard tissue growth, and wherein the amino acid may be in the D- or L-configuration. The ‘558 claims teach the peptide is a peptide of SEQ ID NO:21. It should be noted that the peptide of SEQ ID NO: 21 is 100% identical to the peptide of SEQ ID NO: 1 recited in the instant claim. The ‘558 claims teach that the subject can also have rheumatoid arthritis.
The ’558 claims do not teach imaging obtaining a first prior to locally injecting the peptide and obtaining a second image after the injecting.
Roemer et al. teach that the art has MRI based semi-quantitative scoring of knee osteoarthritis is a valuable method for performing multi-feature joint assessments and of the whole joint in the clinical environment (See page 274). Roemer et al. teach that semiquantitative MRI assessment of osteoarthritis is a valid, reliable, and responsive which helps investigators to evaluate potential new drugs for osteoarthritis (See abstract and page 287). Roemer et al. teach that these SQ scoring systems have been applied to several interventional clinical trials (See page 288).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to obtain images of the joint before and after administration of the peptide as a means for evaluating the efficacy of the peptide, and to determine if further treatment is needed. Given that the ‘558 claims teach examining the area of the patient to determine a change in cartilage relative to a time prior to the administering, it would be obvious to one of ordinary skill in the art to use a known imaging technique, such as MRI, to determine change in cartilage by comparing images of the joint before and after the administration of the peptide to assess efficacy of the peptide and to determine the need for further treatment. Further, it would have been obvious to measure the bone shape of the joint before and after treatment with the peptide to assess the efficacy of the peptide.
Regarding the limitations “reducing joint pain by impacting a 3D shape change of bone underlying articular cartilage in the affected joint”, and “delaying, arresting, or reversing naturally occurring aging of a joint”, the aforementioned limitations are inherent properties that necessarily flow from administering the peptide to a subject having osteoarthritis. That is, the prior art method administers the same peptide, in the same manner, to the same patient population, and thus, would have the same outcome of impacting a 3D shape change of bone underlying cartilage in an affected joint, and delaying, arresting, or reversing naturally occurring aging of a joint, as recited in the instant claims. "Products of identical chemical composition can not 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. Id.
Claim Status
No claims are allowed.
Conclusion
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/SANDRA CARTER/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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